User login
Fibrosis Risk High in Young Adults With Both Obesity and T2D
TOPLINE:
METHODOLOGY:
- Researchers aimed to assess the prevalence of hepatic steatosis and clinically significant fibrosis (stage ≥ 2) in young adults without a history of metabolic dysfunction–associated steatotic liver disease (MASLD), hypothesizing that the rates would be comparable with those in older adults, especially in the presence of cardiometabolic risk factors.
- Overall, 1420 participants aged 21-79 years with or without T2D (63% or 37%, respectively) were included from outpatient clinics at the University of Florida, Gainesville, Florida, and divided into two age groups: < 45 years (n = 243) and ≥ 45 years (n = 1177).
- All the participants underwent assessment of liver stiffness via transient elastography, with magnetic resonance elastography (MRE) or liver biopsy recommended when indicated.
- Participants also underwent a medical history review, physical examination, and fasting blood tests to rule out secondary causes of liver disease.
TAKEAWAY:
- Overall, 52% of participants had hepatic steatosis, and 9.5% had clinically significant fibrosis.
- There were no significant differences in the frequencies of hepatic steatosis (50.2% vs 52.7%; P = .6) or clinically significant hepatic fibrosis (7.5% vs 9.9%; P = .2) observed between young and older adults.
- The presence of either T2D or obesity was linked to an increased prevalence of both hepatic steatosis and fibrosis in both the age groups (P < .01).
- In young and older adults, the presence of both T2D and obesity led to the highest rates of both hepatic steatosis and clinically significant fibrosis, with the latter rate being statistically similar between the groups (15.7% vs 17.3%; P = .2).
- The presence of T2D and obesity was the strongest risk factors for hepatic fibrosis in young adults (odds ratios, 4.33 and 1.16, respectively; P < .05 for both).
IN PRACTICE:
“The clinical implication is that young adults with obesity and T2D carry a high risk of future cirrhosis, possibly as high as older adults, and must be aggressively screened at the first visit and carefully followed,” the authors wrote.
SOURCE:
This study, led by Anu Sharma, University of Florida College of Medicine, Gainesville, was published online in Obesity.
LIMITATIONS:
The diagnosis of clinically significant hepatic fibrosis was confirmed via MRE and/or liver biopsy in only 30% of all participants. The study population included a slightly higher proportion of young adults with obesity, T2D, and other cardiometabolic risk factors than that in national averages, which may have limited its generalizability. Genetic variants associated with MASLD were not included in this study.
DISCLOSURES:
This study was funded partly by grants from the National Institutes of Health and Echosens. One author disclosed receiving research support and serving as a consultant for various pharmaceutical companies.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers aimed to assess the prevalence of hepatic steatosis and clinically significant fibrosis (stage ≥ 2) in young adults without a history of metabolic dysfunction–associated steatotic liver disease (MASLD), hypothesizing that the rates would be comparable with those in older adults, especially in the presence of cardiometabolic risk factors.
- Overall, 1420 participants aged 21-79 years with or without T2D (63% or 37%, respectively) were included from outpatient clinics at the University of Florida, Gainesville, Florida, and divided into two age groups: < 45 years (n = 243) and ≥ 45 years (n = 1177).
- All the participants underwent assessment of liver stiffness via transient elastography, with magnetic resonance elastography (MRE) or liver biopsy recommended when indicated.
- Participants also underwent a medical history review, physical examination, and fasting blood tests to rule out secondary causes of liver disease.
TAKEAWAY:
- Overall, 52% of participants had hepatic steatosis, and 9.5% had clinically significant fibrosis.
- There were no significant differences in the frequencies of hepatic steatosis (50.2% vs 52.7%; P = .6) or clinically significant hepatic fibrosis (7.5% vs 9.9%; P = .2) observed between young and older adults.
- The presence of either T2D or obesity was linked to an increased prevalence of both hepatic steatosis and fibrosis in both the age groups (P < .01).
- In young and older adults, the presence of both T2D and obesity led to the highest rates of both hepatic steatosis and clinically significant fibrosis, with the latter rate being statistically similar between the groups (15.7% vs 17.3%; P = .2).
- The presence of T2D and obesity was the strongest risk factors for hepatic fibrosis in young adults (odds ratios, 4.33 and 1.16, respectively; P < .05 for both).
IN PRACTICE:
“The clinical implication is that young adults with obesity and T2D carry a high risk of future cirrhosis, possibly as high as older adults, and must be aggressively screened at the first visit and carefully followed,” the authors wrote.
SOURCE:
This study, led by Anu Sharma, University of Florida College of Medicine, Gainesville, was published online in Obesity.
LIMITATIONS:
The diagnosis of clinically significant hepatic fibrosis was confirmed via MRE and/or liver biopsy in only 30% of all participants. The study population included a slightly higher proportion of young adults with obesity, T2D, and other cardiometabolic risk factors than that in national averages, which may have limited its generalizability. Genetic variants associated with MASLD were not included in this study.
DISCLOSURES:
This study was funded partly by grants from the National Institutes of Health and Echosens. One author disclosed receiving research support and serving as a consultant for various pharmaceutical companies.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers aimed to assess the prevalence of hepatic steatosis and clinically significant fibrosis (stage ≥ 2) in young adults without a history of metabolic dysfunction–associated steatotic liver disease (MASLD), hypothesizing that the rates would be comparable with those in older adults, especially in the presence of cardiometabolic risk factors.
- Overall, 1420 participants aged 21-79 years with or without T2D (63% or 37%, respectively) were included from outpatient clinics at the University of Florida, Gainesville, Florida, and divided into two age groups: < 45 years (n = 243) and ≥ 45 years (n = 1177).
- All the participants underwent assessment of liver stiffness via transient elastography, with magnetic resonance elastography (MRE) or liver biopsy recommended when indicated.
- Participants also underwent a medical history review, physical examination, and fasting blood tests to rule out secondary causes of liver disease.
TAKEAWAY:
- Overall, 52% of participants had hepatic steatosis, and 9.5% had clinically significant fibrosis.
- There were no significant differences in the frequencies of hepatic steatosis (50.2% vs 52.7%; P = .6) or clinically significant hepatic fibrosis (7.5% vs 9.9%; P = .2) observed between young and older adults.
- The presence of either T2D or obesity was linked to an increased prevalence of both hepatic steatosis and fibrosis in both the age groups (P < .01).
- In young and older adults, the presence of both T2D and obesity led to the highest rates of both hepatic steatosis and clinically significant fibrosis, with the latter rate being statistically similar between the groups (15.7% vs 17.3%; P = .2).
- The presence of T2D and obesity was the strongest risk factors for hepatic fibrosis in young adults (odds ratios, 4.33 and 1.16, respectively; P < .05 for both).
IN PRACTICE:
“The clinical implication is that young adults with obesity and T2D carry a high risk of future cirrhosis, possibly as high as older adults, and must be aggressively screened at the first visit and carefully followed,” the authors wrote.
SOURCE:
This study, led by Anu Sharma, University of Florida College of Medicine, Gainesville, was published online in Obesity.
LIMITATIONS:
The diagnosis of clinically significant hepatic fibrosis was confirmed via MRE and/or liver biopsy in only 30% of all participants. The study population included a slightly higher proportion of young adults with obesity, T2D, and other cardiometabolic risk factors than that in national averages, which may have limited its generalizability. Genetic variants associated with MASLD were not included in this study.
DISCLOSURES:
This study was funded partly by grants from the National Institutes of Health and Echosens. One author disclosed receiving research support and serving as a consultant for various pharmaceutical companies.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
AI Tool Identifies Undiagnosed Early-Stage MASLD
SAN DIEGO — according to new research.
Among the patients identified by the algorithm as meeting the criteria for MASLD, only a small percentage had an MASLD-associated diagnostic code.
“A significant portion of patients who meet criteria for MASLD go undiagnosed, which can lead to delays in care and progression to advanced liver disease,” said lead author Ariana Stuart, MD, an internal medicine resident at the University of Washington, Seattle, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
“However, people shouldn’t interpret our findings as a lack of primary care training or management,” she said. “Instead, this study indicates that AI can complement physician workflow and address the limitations of traditional clinical practice.”
Developing an MASLD Algorithm
Typically, the identification of MASLD has relied on clinician recognition and descriptions in chart notes, Stuart said. Early-stage disease often goes unnoticed, particularly if patients remain asymptomatic, until cirrhosis develops.
To address this, Stuart and colleagues created a machine learning, natural language processing AI algorithm on the basis of MASLD criteria from AASLD: Hepatic steatosis on imaging and at least one metabolic factor (elevated body mass index, hypertension, prediabetes or diabetes, or dyslipidemia). The model was validated by two physicians, who manually reviewed monthly cohorts generated by the algorithm.
Between December 2023 and May 2024, the researchers used the algorithm to analyze an MASLD cohort from medical centers in the Seattle area. The mean age was 51 years, 44% were women, and 68% were White. Those with alcohol-associated liver disease, metastatic malignancy, and autoimmune, genetic, and infectious causes of liver disease were excluded.
The algorithm identified 957 patients with imaging that matched MASLD criteria.
Among those, 137 patients (17%) identified by the algorithm had an MASLD-associated diagnostic code. For these patients, the mean time from initial imaging with steatosis to diagnosis was 33 days, according to patient records.
An additional 26 patients received an MASLD diagnosis during the study period, with a mean time to diagnosis of 56.2 days.
In terms of patient management, 245 patients (26%) had contact with a gastroenterologist or hepatologist based on documentation of a letter, phone call, or office visit. In addition, 546 patients (57%) were screened for hepatitis C.
After adjusting for an over-inclusion error rate of 12.8% and an overdiagnosis rate of 0.02%, the research team found 697 patients (83%) lacked a relevant diagnosis. After multiple iterations, the algorithm achieved an accuracy of about 88%, Stuart said.
Considering Future AI Use
Stuart and colleagues are now testing the algorithm in larger groups and across longer periods.
After that, they intend to implement a quality improvement program to increase awareness for clinicians and primary care providers, as well as train users on how to interpret and move forward with findings of hepatic steatosis in patient records.
For instance, future AI models could flag patients for additional testing, improve chart review, and aid in research efforts around cardiometabolic comorbidities associated with MASLD, she said.
Looking ahead, AI tools such as these represent what’s possible for advancements in research, patient care, and clinical workflows, said Ashley Spann, MD, assistant professor and transplant hepatologist at Vanderbilt University, Nashville, Tennessee, and director of clinical research informatics for Vanderbilt’s Gastroenterology Division.
“AI, in my view, is actually augmented intelligence,” she added. “We need to think about the people and processes involved.”
Spann, who spoke about the use of AI tools in medicine in general, stressed the need for transparency in AI use, careful validation of input-output data, frameworks for machine learning models in medicine, and standardization across institutions.
“What we ultimately need is an infrastructure that supports the simultaneous deployment and evaluation of these models,” she said. “We all need to be on the same page and make sure our models work in multiple settings and make adjustments based on algorithmovigilance afterward.”
Stuart reported no relevant disclosures. Spann serves on Epic’s hepatology steering board, which has focused on how to use AI tools in electronic medical records.
A version of this article appeared on Medscape.com.
SAN DIEGO — according to new research.
Among the patients identified by the algorithm as meeting the criteria for MASLD, only a small percentage had an MASLD-associated diagnostic code.
“A significant portion of patients who meet criteria for MASLD go undiagnosed, which can lead to delays in care and progression to advanced liver disease,” said lead author Ariana Stuart, MD, an internal medicine resident at the University of Washington, Seattle, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
“However, people shouldn’t interpret our findings as a lack of primary care training or management,” she said. “Instead, this study indicates that AI can complement physician workflow and address the limitations of traditional clinical practice.”
Developing an MASLD Algorithm
Typically, the identification of MASLD has relied on clinician recognition and descriptions in chart notes, Stuart said. Early-stage disease often goes unnoticed, particularly if patients remain asymptomatic, until cirrhosis develops.
To address this, Stuart and colleagues created a machine learning, natural language processing AI algorithm on the basis of MASLD criteria from AASLD: Hepatic steatosis on imaging and at least one metabolic factor (elevated body mass index, hypertension, prediabetes or diabetes, or dyslipidemia). The model was validated by two physicians, who manually reviewed monthly cohorts generated by the algorithm.
Between December 2023 and May 2024, the researchers used the algorithm to analyze an MASLD cohort from medical centers in the Seattle area. The mean age was 51 years, 44% were women, and 68% were White. Those with alcohol-associated liver disease, metastatic malignancy, and autoimmune, genetic, and infectious causes of liver disease were excluded.
The algorithm identified 957 patients with imaging that matched MASLD criteria.
Among those, 137 patients (17%) identified by the algorithm had an MASLD-associated diagnostic code. For these patients, the mean time from initial imaging with steatosis to diagnosis was 33 days, according to patient records.
An additional 26 patients received an MASLD diagnosis during the study period, with a mean time to diagnosis of 56.2 days.
In terms of patient management, 245 patients (26%) had contact with a gastroenterologist or hepatologist based on documentation of a letter, phone call, or office visit. In addition, 546 patients (57%) were screened for hepatitis C.
After adjusting for an over-inclusion error rate of 12.8% and an overdiagnosis rate of 0.02%, the research team found 697 patients (83%) lacked a relevant diagnosis. After multiple iterations, the algorithm achieved an accuracy of about 88%, Stuart said.
Considering Future AI Use
Stuart and colleagues are now testing the algorithm in larger groups and across longer periods.
After that, they intend to implement a quality improvement program to increase awareness for clinicians and primary care providers, as well as train users on how to interpret and move forward with findings of hepatic steatosis in patient records.
For instance, future AI models could flag patients for additional testing, improve chart review, and aid in research efforts around cardiometabolic comorbidities associated with MASLD, she said.
Looking ahead, AI tools such as these represent what’s possible for advancements in research, patient care, and clinical workflows, said Ashley Spann, MD, assistant professor and transplant hepatologist at Vanderbilt University, Nashville, Tennessee, and director of clinical research informatics for Vanderbilt’s Gastroenterology Division.
“AI, in my view, is actually augmented intelligence,” she added. “We need to think about the people and processes involved.”
Spann, who spoke about the use of AI tools in medicine in general, stressed the need for transparency in AI use, careful validation of input-output data, frameworks for machine learning models in medicine, and standardization across institutions.
“What we ultimately need is an infrastructure that supports the simultaneous deployment and evaluation of these models,” she said. “We all need to be on the same page and make sure our models work in multiple settings and make adjustments based on algorithmovigilance afterward.”
Stuart reported no relevant disclosures. Spann serves on Epic’s hepatology steering board, which has focused on how to use AI tools in electronic medical records.
A version of this article appeared on Medscape.com.
SAN DIEGO — according to new research.
Among the patients identified by the algorithm as meeting the criteria for MASLD, only a small percentage had an MASLD-associated diagnostic code.
“A significant portion of patients who meet criteria for MASLD go undiagnosed, which can lead to delays in care and progression to advanced liver disease,” said lead author Ariana Stuart, MD, an internal medicine resident at the University of Washington, Seattle, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
“However, people shouldn’t interpret our findings as a lack of primary care training or management,” she said. “Instead, this study indicates that AI can complement physician workflow and address the limitations of traditional clinical practice.”
Developing an MASLD Algorithm
Typically, the identification of MASLD has relied on clinician recognition and descriptions in chart notes, Stuart said. Early-stage disease often goes unnoticed, particularly if patients remain asymptomatic, until cirrhosis develops.
To address this, Stuart and colleagues created a machine learning, natural language processing AI algorithm on the basis of MASLD criteria from AASLD: Hepatic steatosis on imaging and at least one metabolic factor (elevated body mass index, hypertension, prediabetes or diabetes, or dyslipidemia). The model was validated by two physicians, who manually reviewed monthly cohorts generated by the algorithm.
Between December 2023 and May 2024, the researchers used the algorithm to analyze an MASLD cohort from medical centers in the Seattle area. The mean age was 51 years, 44% were women, and 68% were White. Those with alcohol-associated liver disease, metastatic malignancy, and autoimmune, genetic, and infectious causes of liver disease were excluded.
The algorithm identified 957 patients with imaging that matched MASLD criteria.
Among those, 137 patients (17%) identified by the algorithm had an MASLD-associated diagnostic code. For these patients, the mean time from initial imaging with steatosis to diagnosis was 33 days, according to patient records.
An additional 26 patients received an MASLD diagnosis during the study period, with a mean time to diagnosis of 56.2 days.
In terms of patient management, 245 patients (26%) had contact with a gastroenterologist or hepatologist based on documentation of a letter, phone call, or office visit. In addition, 546 patients (57%) were screened for hepatitis C.
After adjusting for an over-inclusion error rate of 12.8% and an overdiagnosis rate of 0.02%, the research team found 697 patients (83%) lacked a relevant diagnosis. After multiple iterations, the algorithm achieved an accuracy of about 88%, Stuart said.
Considering Future AI Use
Stuart and colleagues are now testing the algorithm in larger groups and across longer periods.
After that, they intend to implement a quality improvement program to increase awareness for clinicians and primary care providers, as well as train users on how to interpret and move forward with findings of hepatic steatosis in patient records.
For instance, future AI models could flag patients for additional testing, improve chart review, and aid in research efforts around cardiometabolic comorbidities associated with MASLD, she said.
Looking ahead, AI tools such as these represent what’s possible for advancements in research, patient care, and clinical workflows, said Ashley Spann, MD, assistant professor and transplant hepatologist at Vanderbilt University, Nashville, Tennessee, and director of clinical research informatics for Vanderbilt’s Gastroenterology Division.
“AI, in my view, is actually augmented intelligence,” she added. “We need to think about the people and processes involved.”
Spann, who spoke about the use of AI tools in medicine in general, stressed the need for transparency in AI use, careful validation of input-output data, frameworks for machine learning models in medicine, and standardization across institutions.
“What we ultimately need is an infrastructure that supports the simultaneous deployment and evaluation of these models,” she said. “We all need to be on the same page and make sure our models work in multiple settings and make adjustments based on algorithmovigilance afterward.”
Stuart reported no relevant disclosures. Spann serves on Epic’s hepatology steering board, which has focused on how to use AI tools in electronic medical records.
A version of this article appeared on Medscape.com.
FROM AASLD 24
MELD 3.0 Reduces Sex-Based Liver Transplant Disparities
SAN DIEGO — , according to new research.
In particular, women are now more likely to be added to the waitlist for a liver transplant, more likely to receive a transplant, and less likely to fall off the waitlist because of death.
“MELD 3.0 improved access to transplantation for women, and now waitlist mortality and transplant rates for women more closely approximate the rates for men,” said lead author Allison Kwong, MD, assistant professor of medicine and transplant hepatologist at Stanford Medicine in California.
“Overall transplant outcomes have also improved year over year,” said Kwong, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
Changes in MELD and Transplant Numbers
MELD, which estimates liver failure severity and short-term survival in patients with chronic liver disease, has been used since 2002 to determine organ allocation priority for patients in the United States awaiting liver transplantation. Originally, the score incorporated three variables: creatinine, bilirubin, and the international normalized ratio (INR). MELDNa1, or MELD 2.0, was adopted in 2016 to add sodium.
“Under this system, however, there have been sex-based disparities” with women receiving lower priority scores despite similar disease severity, said Kwong.
“This has been attributed to several factors, such as the creatinine term in the MELD score underestimating renal dysfunction in women, height and body size differences, and differences in disease etiology, and how we’ve assigned exception points historically,” she reported.
Men have had a lower pretransplant mortality rate and higher deceased donor transplant rates, she added.
MELD 3.0 was developed to address these gender differences and other determinants of waitlist outcomes. The updated equation added 1.33 points for women, as well as adding other variables, such as albumin, interactions between bilirubin and sodium, and interactions between albumin and creatinine, to increase prediction accuracy.
To observe the effects of the new system, Kwong and colleagues analyzed OPTN data for patients aged 12 years or older, focusing on the records of more than 20,300 newly registered liver transplant candidates, and about 18,700 transplant recipients, during the 12 months before and 12 months after MELD 3.0 was implemented.
After the switch, 43.7% of newly registered liver transplant candidates were women, compared with 40.4% before the switch. At registration, the median age was 55, both before and after the change in policy, and the median MELD score changed from 23 to 22 after implementation.
In addition, 42.1% of transplants occurred among women after MELD 3.0 implementation, as compared with 37.3% before. Overall, deceased donor transplant rates were similar for men and women after MELD 3.0 implementation.
The 90-day waitlist dropout rate — patients who died or became too sick to receive a transplant — decreased from 13.5% to 9.1% among women, which may be partially attributable to MELD 3.0, said Kwong.
However, waitlist dropout rates also decreased among men, from 9.8% to 7.4%, probably because of improvements in technology, such as machine perfusion, which have increased the number of available livers, she added.
Disparities Continue to Exist
Some disparities still exist. Although the total median MELD score at transplant decreased from 29 to 27, women still had a higher median score of 29 at transplant, compared with a median score of 27 among men.
“This indicates that there may still be differences in transplant access between the sexes,” Kwong said. “There are still body size differences that can affect the probability of transplant, and this would not be addressed by MELD 3.0.”
Additional transplant disparities exist related to other patient characteristics, such as age, race, and ethnicity.
Future versions of MELD could potentially consider these factors, said session moderator Aleksander Krag, MD, PhD, MBA, professor of clinical medicine at the University of Southern Denmark, Odense, and secretary general of the European Association for the Study of the Liver, 2023-2025.
“There are infinite versions of MELD that can be made,” Kwong said. “It’s still early to see how MELD 3.0 will serve the system, but so far, so good.”
In a comment, Tamar Taddei, MD, professor of medicine in digestive diseases at Yale School of Medicine, New Haven, Connecticut, who comoderated the session, noted the importance of using a MELD score that considers sex-based differences.
This study brings MELD 3.0 to its fruition by reducing the disparities experienced by women who were underserved by the previous scoring systems, she said.
It was lovely to see that MELD 3.0 reduced the disparities with transplants, and also that the waitlist dropout was reduced — for both men and women,” Taddei said. “This change is a no-brainer.”
Kwong, Krag, and Taddei reported no relevant disclosures.
A version of this article appeared on Medscape.com.
SAN DIEGO — , according to new research.
In particular, women are now more likely to be added to the waitlist for a liver transplant, more likely to receive a transplant, and less likely to fall off the waitlist because of death.
“MELD 3.0 improved access to transplantation for women, and now waitlist mortality and transplant rates for women more closely approximate the rates for men,” said lead author Allison Kwong, MD, assistant professor of medicine and transplant hepatologist at Stanford Medicine in California.
“Overall transplant outcomes have also improved year over year,” said Kwong, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
Changes in MELD and Transplant Numbers
MELD, which estimates liver failure severity and short-term survival in patients with chronic liver disease, has been used since 2002 to determine organ allocation priority for patients in the United States awaiting liver transplantation. Originally, the score incorporated three variables: creatinine, bilirubin, and the international normalized ratio (INR). MELDNa1, or MELD 2.0, was adopted in 2016 to add sodium.
“Under this system, however, there have been sex-based disparities” with women receiving lower priority scores despite similar disease severity, said Kwong.
“This has been attributed to several factors, such as the creatinine term in the MELD score underestimating renal dysfunction in women, height and body size differences, and differences in disease etiology, and how we’ve assigned exception points historically,” she reported.
Men have had a lower pretransplant mortality rate and higher deceased donor transplant rates, she added.
MELD 3.0 was developed to address these gender differences and other determinants of waitlist outcomes. The updated equation added 1.33 points for women, as well as adding other variables, such as albumin, interactions between bilirubin and sodium, and interactions between albumin and creatinine, to increase prediction accuracy.
To observe the effects of the new system, Kwong and colleagues analyzed OPTN data for patients aged 12 years or older, focusing on the records of more than 20,300 newly registered liver transplant candidates, and about 18,700 transplant recipients, during the 12 months before and 12 months after MELD 3.0 was implemented.
After the switch, 43.7% of newly registered liver transplant candidates were women, compared with 40.4% before the switch. At registration, the median age was 55, both before and after the change in policy, and the median MELD score changed from 23 to 22 after implementation.
In addition, 42.1% of transplants occurred among women after MELD 3.0 implementation, as compared with 37.3% before. Overall, deceased donor transplant rates were similar for men and women after MELD 3.0 implementation.
The 90-day waitlist dropout rate — patients who died or became too sick to receive a transplant — decreased from 13.5% to 9.1% among women, which may be partially attributable to MELD 3.0, said Kwong.
However, waitlist dropout rates also decreased among men, from 9.8% to 7.4%, probably because of improvements in technology, such as machine perfusion, which have increased the number of available livers, she added.
Disparities Continue to Exist
Some disparities still exist. Although the total median MELD score at transplant decreased from 29 to 27, women still had a higher median score of 29 at transplant, compared with a median score of 27 among men.
“This indicates that there may still be differences in transplant access between the sexes,” Kwong said. “There are still body size differences that can affect the probability of transplant, and this would not be addressed by MELD 3.0.”
Additional transplant disparities exist related to other patient characteristics, such as age, race, and ethnicity.
Future versions of MELD could potentially consider these factors, said session moderator Aleksander Krag, MD, PhD, MBA, professor of clinical medicine at the University of Southern Denmark, Odense, and secretary general of the European Association for the Study of the Liver, 2023-2025.
“There are infinite versions of MELD that can be made,” Kwong said. “It’s still early to see how MELD 3.0 will serve the system, but so far, so good.”
In a comment, Tamar Taddei, MD, professor of medicine in digestive diseases at Yale School of Medicine, New Haven, Connecticut, who comoderated the session, noted the importance of using a MELD score that considers sex-based differences.
This study brings MELD 3.0 to its fruition by reducing the disparities experienced by women who were underserved by the previous scoring systems, she said.
It was lovely to see that MELD 3.0 reduced the disparities with transplants, and also that the waitlist dropout was reduced — for both men and women,” Taddei said. “This change is a no-brainer.”
Kwong, Krag, and Taddei reported no relevant disclosures.
A version of this article appeared on Medscape.com.
SAN DIEGO — , according to new research.
In particular, women are now more likely to be added to the waitlist for a liver transplant, more likely to receive a transplant, and less likely to fall off the waitlist because of death.
“MELD 3.0 improved access to transplantation for women, and now waitlist mortality and transplant rates for women more closely approximate the rates for men,” said lead author Allison Kwong, MD, assistant professor of medicine and transplant hepatologist at Stanford Medicine in California.
“Overall transplant outcomes have also improved year over year,” said Kwong, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
Changes in MELD and Transplant Numbers
MELD, which estimates liver failure severity and short-term survival in patients with chronic liver disease, has been used since 2002 to determine organ allocation priority for patients in the United States awaiting liver transplantation. Originally, the score incorporated three variables: creatinine, bilirubin, and the international normalized ratio (INR). MELDNa1, or MELD 2.0, was adopted in 2016 to add sodium.
“Under this system, however, there have been sex-based disparities” with women receiving lower priority scores despite similar disease severity, said Kwong.
“This has been attributed to several factors, such as the creatinine term in the MELD score underestimating renal dysfunction in women, height and body size differences, and differences in disease etiology, and how we’ve assigned exception points historically,” she reported.
Men have had a lower pretransplant mortality rate and higher deceased donor transplant rates, she added.
MELD 3.0 was developed to address these gender differences and other determinants of waitlist outcomes. The updated equation added 1.33 points for women, as well as adding other variables, such as albumin, interactions between bilirubin and sodium, and interactions between albumin and creatinine, to increase prediction accuracy.
To observe the effects of the new system, Kwong and colleagues analyzed OPTN data for patients aged 12 years or older, focusing on the records of more than 20,300 newly registered liver transplant candidates, and about 18,700 transplant recipients, during the 12 months before and 12 months after MELD 3.0 was implemented.
After the switch, 43.7% of newly registered liver transplant candidates were women, compared with 40.4% before the switch. At registration, the median age was 55, both before and after the change in policy, and the median MELD score changed from 23 to 22 after implementation.
In addition, 42.1% of transplants occurred among women after MELD 3.0 implementation, as compared with 37.3% before. Overall, deceased donor transplant rates were similar for men and women after MELD 3.0 implementation.
The 90-day waitlist dropout rate — patients who died or became too sick to receive a transplant — decreased from 13.5% to 9.1% among women, which may be partially attributable to MELD 3.0, said Kwong.
However, waitlist dropout rates also decreased among men, from 9.8% to 7.4%, probably because of improvements in technology, such as machine perfusion, which have increased the number of available livers, she added.
Disparities Continue to Exist
Some disparities still exist. Although the total median MELD score at transplant decreased from 29 to 27, women still had a higher median score of 29 at transplant, compared with a median score of 27 among men.
“This indicates that there may still be differences in transplant access between the sexes,” Kwong said. “There are still body size differences that can affect the probability of transplant, and this would not be addressed by MELD 3.0.”
Additional transplant disparities exist related to other patient characteristics, such as age, race, and ethnicity.
Future versions of MELD could potentially consider these factors, said session moderator Aleksander Krag, MD, PhD, MBA, professor of clinical medicine at the University of Southern Denmark, Odense, and secretary general of the European Association for the Study of the Liver, 2023-2025.
“There are infinite versions of MELD that can be made,” Kwong said. “It’s still early to see how MELD 3.0 will serve the system, but so far, so good.”
In a comment, Tamar Taddei, MD, professor of medicine in digestive diseases at Yale School of Medicine, New Haven, Connecticut, who comoderated the session, noted the importance of using a MELD score that considers sex-based differences.
This study brings MELD 3.0 to its fruition by reducing the disparities experienced by women who were underserved by the previous scoring systems, she said.
It was lovely to see that MELD 3.0 reduced the disparities with transplants, and also that the waitlist dropout was reduced — for both men and women,” Taddei said. “This change is a no-brainer.”
Kwong, Krag, and Taddei reported no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM AASLD 24
‘Watershed Moment’: Semaglutide Shown to Be Effective in MASH
SAN DIEGO — according to interim results from a phase 3 trial.
At 72 weeks, a 2.4-mg once-weekly subcutaneous dose of semaglutide demonstrated superiority, compared with placebo, for the two primary endpoints: Resolution of steatohepatitis with no worsening of fibrosis and improvement in liver fibrosis with no worsening of steatohepatitis.
“It’s been a long journey. I’ve been working with GLP-1s for 16 years, and it’s great to be able to report the first GLP-1 receptor agonist to demonstrate efficacy in a phase 3 trial for MASH,” said lead author Philip Newsome, MD, PhD, director of the Roger Williams Institute of Liver Studies at King’s College London in England.
“There were also improvements in a slew of other noninvasive markers,” said Newsome, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
Although already seen in a broader context, “it’s nice to see a demonstration of the cardiometabolic benefits in the context of MASH and a reassuring safety profile,” he added.
Interim ESSENCE Trial Analysis
ESSENCE (NCT04822181) is an ongoing multicenter, phase 3 randomized, double-blind, placebo-controlled outcome trial studying semaglutide for the potential treatment of MASH.
The trial includes 1200 participants with biopsy-defined MASH and fibrosis, stages F2 and F3, who were randomized 2:1 to a once-weekly subcutaneous injection of 2.4 mg of semaglutide or placebo for 240 weeks. After initiation, the semaglutide dosage was increased every 4 weeks up to 16 weeks when the full dose (2.4 mg) was reached.
In a planned interim analysis, the trial investigators evaluated the primary endpoints at week 72 for the first 800 participants, with biopsies taken at weeks 1 and 72.
A total of 534 people were randomized to the semaglutide group, including 169 with F2 fibrosis and 365 with F3 fibrosis. Among the 266 participants randomized to placebo, 81 had F2 fibrosis and 185 had F3 fibrosis.
At baseline, the patient characteristics were similar between the groups (mean age, 56 years; body mass index, 34.6). A majority of participants also were White (67.5%), women (57.1%), had type 2 diabetes (55.9%), F3 fibrosis (68.8%), and enhanced liver fibrosis (ELF) scores around 10 (55.5%).
For the first primary endpoint, 62.9% of those in the semaglutide group and 34.1% of those in the placebo group reached resolution of steatohepatitis with no worsening of fibrosis. This represented an estimated difference in responder proportions (EDP) of 28.9%.
In addition, 37% of those in the semaglutide group and 22.5% of those in the placebo group met the second primary endpoint of improvement in liver fibrosis with no worsening of steatohepatitis (EDP, 14.4%).
Among the secondary endpoints, combined resolution of steatohepatitis with a one-stage improvement in liver fibrosis occurred in 32.8% of the semaglutide group and 16.2% of the placebo group (EDP, 16.6%).
In additional analyses, Newsome and colleagues found 20%-40% improvements in liver enzymes and noninvasive fibrosis markers, such as ELF and vibration-controlled transient elastography liver stiffness.
Weight loss was also significant, with a 10.5% reduction in the semaglutide group compared with a 2% reduction in the placebo group.
Cardiometabolic risk factors improved as well, with changes in blood pressure measurements, hemoglobin A1c scores, and cholesterol values.
Although not considered statistically significant, patients in the semaglutide group also reported greater reductions in body pain.
In a safety analysis of 1195 participants at 96 weeks, adverse events, severe adverse events, and discontinuations were similar in both groups. Not surprisingly, gastrointestinal side effects were more commonly reported in the semaglutide group, Newsome said.
Highly Anticipated Results
After Newsome’s presentation, attendees applauded.
Rohit Loomba, MD, a gastroenterologist at the University of California, San Diego, who was not involved with the study, called the results the “highlight of the meeting.”
This sentiment was echoed by Naga Chalasani, MD, AGAF, a gastroenterologist at Indiana University Medical Center, Indianapolis, who called the results a “watershed moment in the MASH field” with “terrific data.”
Based on questions after the presentation, Newsome indicated that future ESSENCE reports would look at certain aspects of the results, such as the 10% weight loss among those in the semaglutide group, as well as the mechanisms of histological and fibrosis improvement.
“We know from other GLP-1 trials that more weight loss occurs in those who don’t have type 2 diabetes, and we’re still running those analyses,” he said. “Weight loss is clearly a major contributor to MASH improvement, but there seem to be some weight-independent effects here, which are likely linked to insulin sensitivity or inflammation. We look forward to presenting those analyses in due course.”
In a comment, Kimberly Ann Brown, MD, AGAF, chief of gastroenterology and hepatology at Henry Ford Health System in Detroit, Michigan, AASLD Foundation chair, and comoderator of the late-breaking abstract session, spoke about the highly anticipated presentation.
“This study was really the pinnacle of this meeting. We’ve all been waiting for this data, in large part because many of our patients are already using these medications,” Brown said. “Seeing the benefit for the liver, as well as lipids and other cardiovascular measures, is so important. Having this confirmatory study will hopefully lead to the availability of the medication for this indication among our patients.”
Newsome reported numerous disclosures, including consultant relationships with pharmaceutical companies, such as Novo Nordisk, Boehringer Ingelheim, and Madrigal Pharmaceuticals. Loomba has research grant relationships with numerous companies, including Hanmi, Gilead, Galmed Pharmaceuticals, Galectin Therapeutics, Eli Lilly, Bristol-Myers Squibb, and Boehringer Ingelheim. Chalasani has consultant relationships with Ipsen, Pfizer, Merck, Altimmune, GSK, Madrigal Pharmaceuticals, and Zydus. Brown reported no relevant disclosures.
A version of this article appeared on Medscape.com.
SAN DIEGO — according to interim results from a phase 3 trial.
At 72 weeks, a 2.4-mg once-weekly subcutaneous dose of semaglutide demonstrated superiority, compared with placebo, for the two primary endpoints: Resolution of steatohepatitis with no worsening of fibrosis and improvement in liver fibrosis with no worsening of steatohepatitis.
“It’s been a long journey. I’ve been working with GLP-1s for 16 years, and it’s great to be able to report the first GLP-1 receptor agonist to demonstrate efficacy in a phase 3 trial for MASH,” said lead author Philip Newsome, MD, PhD, director of the Roger Williams Institute of Liver Studies at King’s College London in England.
“There were also improvements in a slew of other noninvasive markers,” said Newsome, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
Although already seen in a broader context, “it’s nice to see a demonstration of the cardiometabolic benefits in the context of MASH and a reassuring safety profile,” he added.
Interim ESSENCE Trial Analysis
ESSENCE (NCT04822181) is an ongoing multicenter, phase 3 randomized, double-blind, placebo-controlled outcome trial studying semaglutide for the potential treatment of MASH.
The trial includes 1200 participants with biopsy-defined MASH and fibrosis, stages F2 and F3, who were randomized 2:1 to a once-weekly subcutaneous injection of 2.4 mg of semaglutide or placebo for 240 weeks. After initiation, the semaglutide dosage was increased every 4 weeks up to 16 weeks when the full dose (2.4 mg) was reached.
In a planned interim analysis, the trial investigators evaluated the primary endpoints at week 72 for the first 800 participants, with biopsies taken at weeks 1 and 72.
A total of 534 people were randomized to the semaglutide group, including 169 with F2 fibrosis and 365 with F3 fibrosis. Among the 266 participants randomized to placebo, 81 had F2 fibrosis and 185 had F3 fibrosis.
At baseline, the patient characteristics were similar between the groups (mean age, 56 years; body mass index, 34.6). A majority of participants also were White (67.5%), women (57.1%), had type 2 diabetes (55.9%), F3 fibrosis (68.8%), and enhanced liver fibrosis (ELF) scores around 10 (55.5%).
For the first primary endpoint, 62.9% of those in the semaglutide group and 34.1% of those in the placebo group reached resolution of steatohepatitis with no worsening of fibrosis. This represented an estimated difference in responder proportions (EDP) of 28.9%.
In addition, 37% of those in the semaglutide group and 22.5% of those in the placebo group met the second primary endpoint of improvement in liver fibrosis with no worsening of steatohepatitis (EDP, 14.4%).
Among the secondary endpoints, combined resolution of steatohepatitis with a one-stage improvement in liver fibrosis occurred in 32.8% of the semaglutide group and 16.2% of the placebo group (EDP, 16.6%).
In additional analyses, Newsome and colleagues found 20%-40% improvements in liver enzymes and noninvasive fibrosis markers, such as ELF and vibration-controlled transient elastography liver stiffness.
Weight loss was also significant, with a 10.5% reduction in the semaglutide group compared with a 2% reduction in the placebo group.
Cardiometabolic risk factors improved as well, with changes in blood pressure measurements, hemoglobin A1c scores, and cholesterol values.
Although not considered statistically significant, patients in the semaglutide group also reported greater reductions in body pain.
In a safety analysis of 1195 participants at 96 weeks, adverse events, severe adverse events, and discontinuations were similar in both groups. Not surprisingly, gastrointestinal side effects were more commonly reported in the semaglutide group, Newsome said.
Highly Anticipated Results
After Newsome’s presentation, attendees applauded.
Rohit Loomba, MD, a gastroenterologist at the University of California, San Diego, who was not involved with the study, called the results the “highlight of the meeting.”
This sentiment was echoed by Naga Chalasani, MD, AGAF, a gastroenterologist at Indiana University Medical Center, Indianapolis, who called the results a “watershed moment in the MASH field” with “terrific data.”
Based on questions after the presentation, Newsome indicated that future ESSENCE reports would look at certain aspects of the results, such as the 10% weight loss among those in the semaglutide group, as well as the mechanisms of histological and fibrosis improvement.
“We know from other GLP-1 trials that more weight loss occurs in those who don’t have type 2 diabetes, and we’re still running those analyses,” he said. “Weight loss is clearly a major contributor to MASH improvement, but there seem to be some weight-independent effects here, which are likely linked to insulin sensitivity or inflammation. We look forward to presenting those analyses in due course.”
In a comment, Kimberly Ann Brown, MD, AGAF, chief of gastroenterology and hepatology at Henry Ford Health System in Detroit, Michigan, AASLD Foundation chair, and comoderator of the late-breaking abstract session, spoke about the highly anticipated presentation.
“This study was really the pinnacle of this meeting. We’ve all been waiting for this data, in large part because many of our patients are already using these medications,” Brown said. “Seeing the benefit for the liver, as well as lipids and other cardiovascular measures, is so important. Having this confirmatory study will hopefully lead to the availability of the medication for this indication among our patients.”
Newsome reported numerous disclosures, including consultant relationships with pharmaceutical companies, such as Novo Nordisk, Boehringer Ingelheim, and Madrigal Pharmaceuticals. Loomba has research grant relationships with numerous companies, including Hanmi, Gilead, Galmed Pharmaceuticals, Galectin Therapeutics, Eli Lilly, Bristol-Myers Squibb, and Boehringer Ingelheim. Chalasani has consultant relationships with Ipsen, Pfizer, Merck, Altimmune, GSK, Madrigal Pharmaceuticals, and Zydus. Brown reported no relevant disclosures.
A version of this article appeared on Medscape.com.
SAN DIEGO — according to interim results from a phase 3 trial.
At 72 weeks, a 2.4-mg once-weekly subcutaneous dose of semaglutide demonstrated superiority, compared with placebo, for the two primary endpoints: Resolution of steatohepatitis with no worsening of fibrosis and improvement in liver fibrosis with no worsening of steatohepatitis.
“It’s been a long journey. I’ve been working with GLP-1s for 16 years, and it’s great to be able to report the first GLP-1 receptor agonist to demonstrate efficacy in a phase 3 trial for MASH,” said lead author Philip Newsome, MD, PhD, director of the Roger Williams Institute of Liver Studies at King’s College London in England.
“There were also improvements in a slew of other noninvasive markers,” said Newsome, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
Although already seen in a broader context, “it’s nice to see a demonstration of the cardiometabolic benefits in the context of MASH and a reassuring safety profile,” he added.
Interim ESSENCE Trial Analysis
ESSENCE (NCT04822181) is an ongoing multicenter, phase 3 randomized, double-blind, placebo-controlled outcome trial studying semaglutide for the potential treatment of MASH.
The trial includes 1200 participants with biopsy-defined MASH and fibrosis, stages F2 and F3, who were randomized 2:1 to a once-weekly subcutaneous injection of 2.4 mg of semaglutide or placebo for 240 weeks. After initiation, the semaglutide dosage was increased every 4 weeks up to 16 weeks when the full dose (2.4 mg) was reached.
In a planned interim analysis, the trial investigators evaluated the primary endpoints at week 72 for the first 800 participants, with biopsies taken at weeks 1 and 72.
A total of 534 people were randomized to the semaglutide group, including 169 with F2 fibrosis and 365 with F3 fibrosis. Among the 266 participants randomized to placebo, 81 had F2 fibrosis and 185 had F3 fibrosis.
At baseline, the patient characteristics were similar between the groups (mean age, 56 years; body mass index, 34.6). A majority of participants also were White (67.5%), women (57.1%), had type 2 diabetes (55.9%), F3 fibrosis (68.8%), and enhanced liver fibrosis (ELF) scores around 10 (55.5%).
For the first primary endpoint, 62.9% of those in the semaglutide group and 34.1% of those in the placebo group reached resolution of steatohepatitis with no worsening of fibrosis. This represented an estimated difference in responder proportions (EDP) of 28.9%.
In addition, 37% of those in the semaglutide group and 22.5% of those in the placebo group met the second primary endpoint of improvement in liver fibrosis with no worsening of steatohepatitis (EDP, 14.4%).
Among the secondary endpoints, combined resolution of steatohepatitis with a one-stage improvement in liver fibrosis occurred in 32.8% of the semaglutide group and 16.2% of the placebo group (EDP, 16.6%).
In additional analyses, Newsome and colleagues found 20%-40% improvements in liver enzymes and noninvasive fibrosis markers, such as ELF and vibration-controlled transient elastography liver stiffness.
Weight loss was also significant, with a 10.5% reduction in the semaglutide group compared with a 2% reduction in the placebo group.
Cardiometabolic risk factors improved as well, with changes in blood pressure measurements, hemoglobin A1c scores, and cholesterol values.
Although not considered statistically significant, patients in the semaglutide group also reported greater reductions in body pain.
In a safety analysis of 1195 participants at 96 weeks, adverse events, severe adverse events, and discontinuations were similar in both groups. Not surprisingly, gastrointestinal side effects were more commonly reported in the semaglutide group, Newsome said.
Highly Anticipated Results
After Newsome’s presentation, attendees applauded.
Rohit Loomba, MD, a gastroenterologist at the University of California, San Diego, who was not involved with the study, called the results the “highlight of the meeting.”
This sentiment was echoed by Naga Chalasani, MD, AGAF, a gastroenterologist at Indiana University Medical Center, Indianapolis, who called the results a “watershed moment in the MASH field” with “terrific data.”
Based on questions after the presentation, Newsome indicated that future ESSENCE reports would look at certain aspects of the results, such as the 10% weight loss among those in the semaglutide group, as well as the mechanisms of histological and fibrosis improvement.
“We know from other GLP-1 trials that more weight loss occurs in those who don’t have type 2 diabetes, and we’re still running those analyses,” he said. “Weight loss is clearly a major contributor to MASH improvement, but there seem to be some weight-independent effects here, which are likely linked to insulin sensitivity or inflammation. We look forward to presenting those analyses in due course.”
In a comment, Kimberly Ann Brown, MD, AGAF, chief of gastroenterology and hepatology at Henry Ford Health System in Detroit, Michigan, AASLD Foundation chair, and comoderator of the late-breaking abstract session, spoke about the highly anticipated presentation.
“This study was really the pinnacle of this meeting. We’ve all been waiting for this data, in large part because many of our patients are already using these medications,” Brown said. “Seeing the benefit for the liver, as well as lipids and other cardiovascular measures, is so important. Having this confirmatory study will hopefully lead to the availability of the medication for this indication among our patients.”
Newsome reported numerous disclosures, including consultant relationships with pharmaceutical companies, such as Novo Nordisk, Boehringer Ingelheim, and Madrigal Pharmaceuticals. Loomba has research grant relationships with numerous companies, including Hanmi, Gilead, Galmed Pharmaceuticals, Galectin Therapeutics, Eli Lilly, Bristol-Myers Squibb, and Boehringer Ingelheim. Chalasani has consultant relationships with Ipsen, Pfizer, Merck, Altimmune, GSK, Madrigal Pharmaceuticals, and Zydus. Brown reported no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM AASLD 24
US Alcohol-Related Deaths Double Over 2 Decades, With Notable Age and Gender Disparities
TOPLINE:
US alcohol-related mortality rates increased from 10.7 to 21.6 per 100,000 between 1999 and 2020, with the largest rise of 3.8-fold observed in adults aged 25-34 years. Women experienced a 2.5-fold increase, while the Midwest region showed a similar rise in mortality rates.
METHODOLOGY:
- Analysis utilized the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research to examine alcohol-related mortality trends from 1999 to 2020.
- Researchers analyzed data from a total US population of 180,408,769 people aged 25 to 85+ years in 1999 and 226,635,013 people in 2020.
- International Classification of Diseases, Tenth Revision, codes were used to identify deaths with alcohol attribution, including mental and behavioral disorders, alcoholic organ damage, and alcohol-related poisoning.
TAKEAWAY:
- Overall mortality rates increased from 10.7 (95% CI, 10.6-10.8) per 100,000 in 1999 to 21.6 (95% CI, 21.4-21.8) per 100,000 in 2020, representing a significant twofold increase.
- Adults aged 55-64 years demonstrated both the steepest increase and highest absolute rates in both 1999 and 2020.
- American Indian and Alaska Native individuals experienced the steepest increase and highest absolute rates among all racial groups.
- The West region maintained the highest absolute rates in both 1999 and 2020, despite the Midwest showing the largest increase.
IN PRACTICE:
“Individuals who consume large amounts of alcohol tend to have the highest risks of total mortality as well as deaths from cardiovascular disease. Cardiovascular disease deaths are predominantly due to myocardial infarction and stroke. To mitigate these risks, health providers may wish to implement screening for alcohol use in primary care and other healthcare settings. By providing brief interventions and referrals to treatment, healthcare providers would be able to achieve the early identification of individuals at risk of alcohol-related harm and offer them the support and resources they need to reduce their alcohol consumption,” wrote the authors of the study.
SOURCE:
The study was led by Alexandra Matarazzo, BS, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton. It was published online in The American Journal of Medicine.
LIMITATIONS:
According to the authors, the cross-sectional nature of the data limits the study to descriptive analysis only, making it suitable for hypothesis generation but not hypothesis testing. While the validity and generalizability within the United States are secure because of the use of complete population data, potential bias and uncontrolled confounding may exist because of different population mixes between the two time points.
DISCLOSURES:
The authors reported no relevant conflicts of interest. One coauthor disclosed serving as an independent scientist in an advisory role to investigators and sponsors as Chair of Data Monitoring Committees for Amgen and UBC, to the Food and Drug Administration, and to Up to Date. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
US alcohol-related mortality rates increased from 10.7 to 21.6 per 100,000 between 1999 and 2020, with the largest rise of 3.8-fold observed in adults aged 25-34 years. Women experienced a 2.5-fold increase, while the Midwest region showed a similar rise in mortality rates.
METHODOLOGY:
- Analysis utilized the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research to examine alcohol-related mortality trends from 1999 to 2020.
- Researchers analyzed data from a total US population of 180,408,769 people aged 25 to 85+ years in 1999 and 226,635,013 people in 2020.
- International Classification of Diseases, Tenth Revision, codes were used to identify deaths with alcohol attribution, including mental and behavioral disorders, alcoholic organ damage, and alcohol-related poisoning.
TAKEAWAY:
- Overall mortality rates increased from 10.7 (95% CI, 10.6-10.8) per 100,000 in 1999 to 21.6 (95% CI, 21.4-21.8) per 100,000 in 2020, representing a significant twofold increase.
- Adults aged 55-64 years demonstrated both the steepest increase and highest absolute rates in both 1999 and 2020.
- American Indian and Alaska Native individuals experienced the steepest increase and highest absolute rates among all racial groups.
- The West region maintained the highest absolute rates in both 1999 and 2020, despite the Midwest showing the largest increase.
IN PRACTICE:
“Individuals who consume large amounts of alcohol tend to have the highest risks of total mortality as well as deaths from cardiovascular disease. Cardiovascular disease deaths are predominantly due to myocardial infarction and stroke. To mitigate these risks, health providers may wish to implement screening for alcohol use in primary care and other healthcare settings. By providing brief interventions and referrals to treatment, healthcare providers would be able to achieve the early identification of individuals at risk of alcohol-related harm and offer them the support and resources they need to reduce their alcohol consumption,” wrote the authors of the study.
SOURCE:
The study was led by Alexandra Matarazzo, BS, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton. It was published online in The American Journal of Medicine.
LIMITATIONS:
According to the authors, the cross-sectional nature of the data limits the study to descriptive analysis only, making it suitable for hypothesis generation but not hypothesis testing. While the validity and generalizability within the United States are secure because of the use of complete population data, potential bias and uncontrolled confounding may exist because of different population mixes between the two time points.
DISCLOSURES:
The authors reported no relevant conflicts of interest. One coauthor disclosed serving as an independent scientist in an advisory role to investigators and sponsors as Chair of Data Monitoring Committees for Amgen and UBC, to the Food and Drug Administration, and to Up to Date. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
US alcohol-related mortality rates increased from 10.7 to 21.6 per 100,000 between 1999 and 2020, with the largest rise of 3.8-fold observed in adults aged 25-34 years. Women experienced a 2.5-fold increase, while the Midwest region showed a similar rise in mortality rates.
METHODOLOGY:
- Analysis utilized the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research to examine alcohol-related mortality trends from 1999 to 2020.
- Researchers analyzed data from a total US population of 180,408,769 people aged 25 to 85+ years in 1999 and 226,635,013 people in 2020.
- International Classification of Diseases, Tenth Revision, codes were used to identify deaths with alcohol attribution, including mental and behavioral disorders, alcoholic organ damage, and alcohol-related poisoning.
TAKEAWAY:
- Overall mortality rates increased from 10.7 (95% CI, 10.6-10.8) per 100,000 in 1999 to 21.6 (95% CI, 21.4-21.8) per 100,000 in 2020, representing a significant twofold increase.
- Adults aged 55-64 years demonstrated both the steepest increase and highest absolute rates in both 1999 and 2020.
- American Indian and Alaska Native individuals experienced the steepest increase and highest absolute rates among all racial groups.
- The West region maintained the highest absolute rates in both 1999 and 2020, despite the Midwest showing the largest increase.
IN PRACTICE:
“Individuals who consume large amounts of alcohol tend to have the highest risks of total mortality as well as deaths from cardiovascular disease. Cardiovascular disease deaths are predominantly due to myocardial infarction and stroke. To mitigate these risks, health providers may wish to implement screening for alcohol use in primary care and other healthcare settings. By providing brief interventions and referrals to treatment, healthcare providers would be able to achieve the early identification of individuals at risk of alcohol-related harm and offer them the support and resources they need to reduce their alcohol consumption,” wrote the authors of the study.
SOURCE:
The study was led by Alexandra Matarazzo, BS, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton. It was published online in The American Journal of Medicine.
LIMITATIONS:
According to the authors, the cross-sectional nature of the data limits the study to descriptive analysis only, making it suitable for hypothesis generation but not hypothesis testing. While the validity and generalizability within the United States are secure because of the use of complete population data, potential bias and uncontrolled confounding may exist because of different population mixes between the two time points.
DISCLOSURES:
The authors reported no relevant conflicts of interest. One coauthor disclosed serving as an independent scientist in an advisory role to investigators and sponsors as Chair of Data Monitoring Committees for Amgen and UBC, to the Food and Drug Administration, and to Up to Date. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Deprescribe Low-Value Meds to Reduce Polypharmacy Harms
VANCOUVER, BRITISH COLUMBIA — While polypharmacy is inevitable for patients with multiple chronic diseases, not all medications improve patient-oriented outcomes, members of the Patients, Experience, Evidence, Research (PEER) team, a group of Canadian primary care professionals who develop evidence-based guidelines, told attendees at the Family Medicine Forum (FMF) 2024.
In a thought-provoking presentation called “Axe the Rx: Deprescribing Chronic Medications with PEER,” the panelists gave examples of medications that may be safely stopped or tapered, particularly for older adults “whose pill bag is heavier than their lunch bag.”
Curbing Cardiovascular Drugs
The 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults call for reaching an LDL-C < 1.8 mmol/L in secondary cardiovascular prevention by potentially adding on medical therapies such as proprotein convertase subtilisin/kexin type 9 inhibitors or ezetimibe or both if that target is not reached with the maximal dosage of a statin.
But family physicians do not need to follow this guidance for their patients who have had a myocardial infarction, said Ontario family physician Jennifer Young, MD, a physician advisor in the Canadian College of Family Physicians’ Knowledge Experts and Tools Program.
Treating to below 1.8 mmol/L “means lab testing for the patients,” Young told this news organization. “It means increasing doses [of a statin] to try and get to that level.” If the patient is already on the highest dose of a statin, it means adding other medications that lower cholesterol.
“If that was translating into better outcomes like [preventing] death and another heart attack, then all of that extra effort would be worth it,” said Young. “But we don’t have evidence that it actually does have a benefit for outcomes like death and repeated heart attacks,” compared with putting them on a high dose of a potent statin.
Tapering Opioids
Before placing patients on an opioid taper, clinicians should first assess them for opioid use disorder (OUD), said Jessica Kirkwood, MD, assistant professor of family medicine at the University of Alberta in Edmonton, Canada. She suggested using the Prescription Opioid Misuse Index questionnaire to do so.
Clinicians should be much more careful in initiating a taper with patients with OUD, said Kirkwood. They must ensure that these patients are motivated to discontinue their opioids. “We’re losing 21 Canadians a day to the opioid crisis. We all know that cutting someone off their opioids and potentially having them seek opioids elsewhere through illicit means can be fatal.”
In addition, clinicians should spend more time counseling patients with OUD than those without, Kirkwood continued. They must explain to these patients how they are being tapered (eg, the intervals and doses) and highlight the benefits of a taper, such as reduced constipation. Opioid agonist therapy (such as methadone or buprenorphine) can be considered in these patients.
Some research has pointed to the importance of patient motivation as a factor in the success of opioid tapers, noted Kirkwood.
Deprescribing Benzodiazepines
Benzodiazepine receptor agonists, too, often can be deprescribed. These drugs should not be prescribed to promote sleep on a long-term basis. Yet clinicians commonly encounter patients who have been taking them for more than a year, said pharmacist Betsy Thomas, assistant adjunct professor of family medicine at the University of Alberta.
The medications “are usually fairly effective for the first couple of weeks to about a month, and then the benefits start to decrease, and we start to see more harms,” she said.
Some of the harms that have been associated with continued use of benzodiazepine receptor agonists include delayed reaction time and impaired cognition, which can affect the ability to drive, the risk for falls, and the risk for hip fractures, she noted. Some research suggests that these drugs are not an option for treating insomnia in patients aged 65 years or older.
Clinicians should encourage tapering the use of benzodiazepine receptor agonists to minimize dependence and transition patients to nonpharmacologic approaches such as cognitive behavioral therapy to manage insomnia, she said. A recent study demonstrated the efficacy of the intervention, and Thomas suggested that family physicians visit the mysleepwell.ca website for more information.
Young, Kirkwood, and Thomas reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
VANCOUVER, BRITISH COLUMBIA — While polypharmacy is inevitable for patients with multiple chronic diseases, not all medications improve patient-oriented outcomes, members of the Patients, Experience, Evidence, Research (PEER) team, a group of Canadian primary care professionals who develop evidence-based guidelines, told attendees at the Family Medicine Forum (FMF) 2024.
In a thought-provoking presentation called “Axe the Rx: Deprescribing Chronic Medications with PEER,” the panelists gave examples of medications that may be safely stopped or tapered, particularly for older adults “whose pill bag is heavier than their lunch bag.”
Curbing Cardiovascular Drugs
The 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults call for reaching an LDL-C < 1.8 mmol/L in secondary cardiovascular prevention by potentially adding on medical therapies such as proprotein convertase subtilisin/kexin type 9 inhibitors or ezetimibe or both if that target is not reached with the maximal dosage of a statin.
But family physicians do not need to follow this guidance for their patients who have had a myocardial infarction, said Ontario family physician Jennifer Young, MD, a physician advisor in the Canadian College of Family Physicians’ Knowledge Experts and Tools Program.
Treating to below 1.8 mmol/L “means lab testing for the patients,” Young told this news organization. “It means increasing doses [of a statin] to try and get to that level.” If the patient is already on the highest dose of a statin, it means adding other medications that lower cholesterol.
“If that was translating into better outcomes like [preventing] death and another heart attack, then all of that extra effort would be worth it,” said Young. “But we don’t have evidence that it actually does have a benefit for outcomes like death and repeated heart attacks,” compared with putting them on a high dose of a potent statin.
Tapering Opioids
Before placing patients on an opioid taper, clinicians should first assess them for opioid use disorder (OUD), said Jessica Kirkwood, MD, assistant professor of family medicine at the University of Alberta in Edmonton, Canada. She suggested using the Prescription Opioid Misuse Index questionnaire to do so.
Clinicians should be much more careful in initiating a taper with patients with OUD, said Kirkwood. They must ensure that these patients are motivated to discontinue their opioids. “We’re losing 21 Canadians a day to the opioid crisis. We all know that cutting someone off their opioids and potentially having them seek opioids elsewhere through illicit means can be fatal.”
In addition, clinicians should spend more time counseling patients with OUD than those without, Kirkwood continued. They must explain to these patients how they are being tapered (eg, the intervals and doses) and highlight the benefits of a taper, such as reduced constipation. Opioid agonist therapy (such as methadone or buprenorphine) can be considered in these patients.
Some research has pointed to the importance of patient motivation as a factor in the success of opioid tapers, noted Kirkwood.
Deprescribing Benzodiazepines
Benzodiazepine receptor agonists, too, often can be deprescribed. These drugs should not be prescribed to promote sleep on a long-term basis. Yet clinicians commonly encounter patients who have been taking them for more than a year, said pharmacist Betsy Thomas, assistant adjunct professor of family medicine at the University of Alberta.
The medications “are usually fairly effective for the first couple of weeks to about a month, and then the benefits start to decrease, and we start to see more harms,” she said.
Some of the harms that have been associated with continued use of benzodiazepine receptor agonists include delayed reaction time and impaired cognition, which can affect the ability to drive, the risk for falls, and the risk for hip fractures, she noted. Some research suggests that these drugs are not an option for treating insomnia in patients aged 65 years or older.
Clinicians should encourage tapering the use of benzodiazepine receptor agonists to minimize dependence and transition patients to nonpharmacologic approaches such as cognitive behavioral therapy to manage insomnia, she said. A recent study demonstrated the efficacy of the intervention, and Thomas suggested that family physicians visit the mysleepwell.ca website for more information.
Young, Kirkwood, and Thomas reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
VANCOUVER, BRITISH COLUMBIA — While polypharmacy is inevitable for patients with multiple chronic diseases, not all medications improve patient-oriented outcomes, members of the Patients, Experience, Evidence, Research (PEER) team, a group of Canadian primary care professionals who develop evidence-based guidelines, told attendees at the Family Medicine Forum (FMF) 2024.
In a thought-provoking presentation called “Axe the Rx: Deprescribing Chronic Medications with PEER,” the panelists gave examples of medications that may be safely stopped or tapered, particularly for older adults “whose pill bag is heavier than their lunch bag.”
Curbing Cardiovascular Drugs
The 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults call for reaching an LDL-C < 1.8 mmol/L in secondary cardiovascular prevention by potentially adding on medical therapies such as proprotein convertase subtilisin/kexin type 9 inhibitors or ezetimibe or both if that target is not reached with the maximal dosage of a statin.
But family physicians do not need to follow this guidance for their patients who have had a myocardial infarction, said Ontario family physician Jennifer Young, MD, a physician advisor in the Canadian College of Family Physicians’ Knowledge Experts and Tools Program.
Treating to below 1.8 mmol/L “means lab testing for the patients,” Young told this news organization. “It means increasing doses [of a statin] to try and get to that level.” If the patient is already on the highest dose of a statin, it means adding other medications that lower cholesterol.
“If that was translating into better outcomes like [preventing] death and another heart attack, then all of that extra effort would be worth it,” said Young. “But we don’t have evidence that it actually does have a benefit for outcomes like death and repeated heart attacks,” compared with putting them on a high dose of a potent statin.
Tapering Opioids
Before placing patients on an opioid taper, clinicians should first assess them for opioid use disorder (OUD), said Jessica Kirkwood, MD, assistant professor of family medicine at the University of Alberta in Edmonton, Canada. She suggested using the Prescription Opioid Misuse Index questionnaire to do so.
Clinicians should be much more careful in initiating a taper with patients with OUD, said Kirkwood. They must ensure that these patients are motivated to discontinue their opioids. “We’re losing 21 Canadians a day to the opioid crisis. We all know that cutting someone off their opioids and potentially having them seek opioids elsewhere through illicit means can be fatal.”
In addition, clinicians should spend more time counseling patients with OUD than those without, Kirkwood continued. They must explain to these patients how they are being tapered (eg, the intervals and doses) and highlight the benefits of a taper, such as reduced constipation. Opioid agonist therapy (such as methadone or buprenorphine) can be considered in these patients.
Some research has pointed to the importance of patient motivation as a factor in the success of opioid tapers, noted Kirkwood.
Deprescribing Benzodiazepines
Benzodiazepine receptor agonists, too, often can be deprescribed. These drugs should not be prescribed to promote sleep on a long-term basis. Yet clinicians commonly encounter patients who have been taking them for more than a year, said pharmacist Betsy Thomas, assistant adjunct professor of family medicine at the University of Alberta.
The medications “are usually fairly effective for the first couple of weeks to about a month, and then the benefits start to decrease, and we start to see more harms,” she said.
Some of the harms that have been associated with continued use of benzodiazepine receptor agonists include delayed reaction time and impaired cognition, which can affect the ability to drive, the risk for falls, and the risk for hip fractures, she noted. Some research suggests that these drugs are not an option for treating insomnia in patients aged 65 years or older.
Clinicians should encourage tapering the use of benzodiazepine receptor agonists to minimize dependence and transition patients to nonpharmacologic approaches such as cognitive behavioral therapy to manage insomnia, she said. A recent study demonstrated the efficacy of the intervention, and Thomas suggested that family physicians visit the mysleepwell.ca website for more information.
Young, Kirkwood, and Thomas reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM FMF 2024
Intermittent Calorie Restriction Reduces Liver Fat in MASLD
TOPLINE:
Intermittent calorie restriction (CR) diet is more effective in reducing liver fat content than a standard-of-care diet in patients with metabolic dysfunction–associated steatotic liver disease (MASLD), especially in those with obesity.
METHODOLOGY:
- Intermittent CR, which involves alternating periods of energy restriction and regular energy intake, has been proposed as a dietary intervention for MASLD.
- Researchers conducted a 12-week randomized controlled trial to compare the effects of a 5:2 intermittent CR and standard-of-care diet in nondiabetic patients with MASLD with or without obesity at an outpatient clinic in Korea.
- Intermittent CR comprised a reduced calorie consumption (500 kcal/d for women and 600 kcal/d for men) on 2 nonconsecutive days a week and, on the remaining 5 days/wk, following the Korean Dietary Reference Intakes (2000 kcal/d for women and 2500 kcal/d for men).
- The standard diet involved the consumption of 80% of the recommended calories (1200-1500 kcal/d for women and 1500-1800 kcal/d for men, or reducing 500-1000 kcal/d).
- The primary outcome was a relative reduction of ≥ 30% in the liver fat content measured by MRI-proton density fat fraction after 12 weeks.
- The secondary outcomes included changes in liver fibrosis, body weight, and body composition from baseline to week 12.
TAKEAWAY:
- Researchers enrolled 72 participants (36 patients with obesity and 36 without), with 63 completing the trial; of these, 32 received an intermittent CR diet (median age, 47.0 years; 58.8% men) and 31 received a standard-of-care diet (median age, 53.0 years; 36.4% men).
- A higher proportion of patients in the intermittent CR group achieved a relative reduction of ≥ 30% in the liver fat content at 12 weeks than the standard-of-care group (72.2% vs 44.4%; P = .033).
- These findings were even more prominent among those with obesity (61.1% in the intermittent CR group vs 27.7% in the standard-of-care group; P = .030).
- Patients with obesity in the intermittent CR group also showed a greater relative reduction in body weight than those in the standard-of-care group (–5.5% vs –2.9%; P = .022).
- Intermittent CR had no apparent effects on body composition, liver enzymes, or the lipid and glucose profiles of those with or without obesity.
IN PRACTICE:
“These results support the recommendation of a 5:2 [intermittent CR] diet as a useful dietary strategy for patients with MASLD,” the authors wrote.
SOURCE:
The study, led by Han Ah Lee, PhD, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, South Korea, was published online in Clinical Gastroenterology and Hepatology.
LIMITATIONS:
The intervention period of 12 weeks was relatively short, limiting the ability to observe long-term effects. The study did not reveal the effects of intermittent CR on histologic metabolic dysfunction–associated steatohepatitis or significantly advanced fibrosis. The study was conducted at a single center located in an urban, metropolitan area in Korea, which may limit the applicability of the findings to other populations.
DISCLOSURES:
This study was supported in part by a grant from the National Research Foundation of Korea funded by the Ministry of Science and ICT. The authors declared no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
TOPLINE:
Intermittent calorie restriction (CR) diet is more effective in reducing liver fat content than a standard-of-care diet in patients with metabolic dysfunction–associated steatotic liver disease (MASLD), especially in those with obesity.
METHODOLOGY:
- Intermittent CR, which involves alternating periods of energy restriction and regular energy intake, has been proposed as a dietary intervention for MASLD.
- Researchers conducted a 12-week randomized controlled trial to compare the effects of a 5:2 intermittent CR and standard-of-care diet in nondiabetic patients with MASLD with or without obesity at an outpatient clinic in Korea.
- Intermittent CR comprised a reduced calorie consumption (500 kcal/d for women and 600 kcal/d for men) on 2 nonconsecutive days a week and, on the remaining 5 days/wk, following the Korean Dietary Reference Intakes (2000 kcal/d for women and 2500 kcal/d for men).
- The standard diet involved the consumption of 80% of the recommended calories (1200-1500 kcal/d for women and 1500-1800 kcal/d for men, or reducing 500-1000 kcal/d).
- The primary outcome was a relative reduction of ≥ 30% in the liver fat content measured by MRI-proton density fat fraction after 12 weeks.
- The secondary outcomes included changes in liver fibrosis, body weight, and body composition from baseline to week 12.
TAKEAWAY:
- Researchers enrolled 72 participants (36 patients with obesity and 36 without), with 63 completing the trial; of these, 32 received an intermittent CR diet (median age, 47.0 years; 58.8% men) and 31 received a standard-of-care diet (median age, 53.0 years; 36.4% men).
- A higher proportion of patients in the intermittent CR group achieved a relative reduction of ≥ 30% in the liver fat content at 12 weeks than the standard-of-care group (72.2% vs 44.4%; P = .033).
- These findings were even more prominent among those with obesity (61.1% in the intermittent CR group vs 27.7% in the standard-of-care group; P = .030).
- Patients with obesity in the intermittent CR group also showed a greater relative reduction in body weight than those in the standard-of-care group (–5.5% vs –2.9%; P = .022).
- Intermittent CR had no apparent effects on body composition, liver enzymes, or the lipid and glucose profiles of those with or without obesity.
IN PRACTICE:
“These results support the recommendation of a 5:2 [intermittent CR] diet as a useful dietary strategy for patients with MASLD,” the authors wrote.
SOURCE:
The study, led by Han Ah Lee, PhD, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, South Korea, was published online in Clinical Gastroenterology and Hepatology.
LIMITATIONS:
The intervention period of 12 weeks was relatively short, limiting the ability to observe long-term effects. The study did not reveal the effects of intermittent CR on histologic metabolic dysfunction–associated steatohepatitis or significantly advanced fibrosis. The study was conducted at a single center located in an urban, metropolitan area in Korea, which may limit the applicability of the findings to other populations.
DISCLOSURES:
This study was supported in part by a grant from the National Research Foundation of Korea funded by the Ministry of Science and ICT. The authors declared no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
TOPLINE:
Intermittent calorie restriction (CR) diet is more effective in reducing liver fat content than a standard-of-care diet in patients with metabolic dysfunction–associated steatotic liver disease (MASLD), especially in those with obesity.
METHODOLOGY:
- Intermittent CR, which involves alternating periods of energy restriction and regular energy intake, has been proposed as a dietary intervention for MASLD.
- Researchers conducted a 12-week randomized controlled trial to compare the effects of a 5:2 intermittent CR and standard-of-care diet in nondiabetic patients with MASLD with or without obesity at an outpatient clinic in Korea.
- Intermittent CR comprised a reduced calorie consumption (500 kcal/d for women and 600 kcal/d for men) on 2 nonconsecutive days a week and, on the remaining 5 days/wk, following the Korean Dietary Reference Intakes (2000 kcal/d for women and 2500 kcal/d for men).
- The standard diet involved the consumption of 80% of the recommended calories (1200-1500 kcal/d for women and 1500-1800 kcal/d for men, or reducing 500-1000 kcal/d).
- The primary outcome was a relative reduction of ≥ 30% in the liver fat content measured by MRI-proton density fat fraction after 12 weeks.
- The secondary outcomes included changes in liver fibrosis, body weight, and body composition from baseline to week 12.
TAKEAWAY:
- Researchers enrolled 72 participants (36 patients with obesity and 36 without), with 63 completing the trial; of these, 32 received an intermittent CR diet (median age, 47.0 years; 58.8% men) and 31 received a standard-of-care diet (median age, 53.0 years; 36.4% men).
- A higher proportion of patients in the intermittent CR group achieved a relative reduction of ≥ 30% in the liver fat content at 12 weeks than the standard-of-care group (72.2% vs 44.4%; P = .033).
- These findings were even more prominent among those with obesity (61.1% in the intermittent CR group vs 27.7% in the standard-of-care group; P = .030).
- Patients with obesity in the intermittent CR group also showed a greater relative reduction in body weight than those in the standard-of-care group (–5.5% vs –2.9%; P = .022).
- Intermittent CR had no apparent effects on body composition, liver enzymes, or the lipid and glucose profiles of those with or without obesity.
IN PRACTICE:
“These results support the recommendation of a 5:2 [intermittent CR] diet as a useful dietary strategy for patients with MASLD,” the authors wrote.
SOURCE:
The study, led by Han Ah Lee, PhD, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, South Korea, was published online in Clinical Gastroenterology and Hepatology.
LIMITATIONS:
The intervention period of 12 weeks was relatively short, limiting the ability to observe long-term effects. The study did not reveal the effects of intermittent CR on histologic metabolic dysfunction–associated steatohepatitis or significantly advanced fibrosis. The study was conducted at a single center located in an urban, metropolitan area in Korea, which may limit the applicability of the findings to other populations.
DISCLOSURES:
This study was supported in part by a grant from the National Research Foundation of Korea funded by the Ministry of Science and ICT. The authors declared no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
Alcohol-Associated Liver Disease and Alcohol Use Disorder on the Rise in Older Adults
SAN DIEGO — according to the results of a new study.
Even as mortality rates decline globally, AUD deaths rose in the United States, increasing 1.63% per year between 2010 and 2019. Deaths from cirrhosis increased by 0.56% each year, and deaths from primary liver cancer associated with alcohol increased by 3.09% per year.
Several factors, such as an aging US population and increasing alcohol consumption, play a major role in the uptick in mortality, said lead author Pojsakorn Danpanichkul, MD, an internal medicine resident at Texas Tech University Health Sciences Center, Lubbock, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
“Healthcare providers should increase screening for alcohol use among older adults and consider the added risks of alcohol consumption. Public health strategies should target alcohol prevention and treatment programs tailored to older adults,” he said.
“Older adults are more vulnerable to the harmful effects of alcohol due to natural declines in liver function and metabolism, leading to a higher risk of liver disease and complications,” he explained. However, “little research has focused on this issue.”
Trends in US Not Seen Globally
Danpanichkul and colleagues analyzed data from the Global Burden of Disease Study for 2010-2019, calculating the annual percent change for the burden of AUD, ALD, and liver cancer from alcohol in patients age 70 and older. The research team then compared data in the United States to global estimates for these same diseases.
In 2019, there were 556,340 cases of AUD, 112,560 cases of ALD, and 3720 cases of liver cancer from alcohol in older adults in the United States. In addition, there were 1750 deaths attributed to AUD, 4860 deaths from ALD, and 3010 deaths caused by primary liver cancer from alcohol.
The age-standardized prevalence rates (ASPRs) per 100,000 people were 1547 cases of AUD, 313 cases of ALD, and 10 cases of primary liver cancer caused by alcohol.
The age-standardized death rates (ASDRs) per 100,000 people were 4.88 for AUD, 13.52 for ALD, and 8.38 for primary liver cancer.
During the time period studied, upward trends occurred in the United States, with annual ASPRs increasing by 2.52% for AUD, 1.78% for ALD, and 3.31% for primary liver cancer due to alcohol. Globally, the trends were lower, with annual increases of 0.2% for AUD, 0.38% for ALD, and 0.67% for primary liver cancer from alcohol.
During the same time, ASDRs also increased in all three categories in the United States, while global trends showed a 0.91% decline in AUD deaths and 0.6% decline in ALD deaths. Liver cancer deaths, however, increased by 0.3% worldwide.
Targeted strategies are essential to reduce this growing health burden, especially in an aging population, Danpanichkul said. “These interventions should focus on early detection, intervention, and management for individuals at risk or already affected by ALD and AUD.”
Future studies should investigate alcohol consumption and mortality trends in other age groups, including by sex, location (such as state or territory), and race and ethnicity, he said. Data for more recent years would be compelling as well.
Increased Alcohol Use During and After Pandemic
Numerous studies have indicated that alcohol use increased in 2020 during the COVID-19 pandemic and has remained elevated since then.
In a study published in the Annals of Internal Medicine, for instance, alcohol use per 100 people increased 2.69% in 2020 and 2.96% in 2022, as compared with 2018. Increases occurred across all subgroups, including age, sex, race, ethnicity, and US region.
“During the COVID-19 pandemic, many people stayed at home, watched the television, and increased their alcohol intake” — in the United States and also in Japan — said Hisanori Muto, MD, senior assistant professor of gastroenterology at Fujita Health University in Nagoya, Japan, who wasn’t involved with this study.
“Although the global numbers may appear lower, we’re also seeing an increase in AUD and ALD in Japan, similar to the United States,” he said. “It’s very important to watch these trends and address these diseases.”
Danpanichkul and Muto reported no relevant disclosures.
A version of this article appeared on Medscape.com.
SAN DIEGO — according to the results of a new study.
Even as mortality rates decline globally, AUD deaths rose in the United States, increasing 1.63% per year between 2010 and 2019. Deaths from cirrhosis increased by 0.56% each year, and deaths from primary liver cancer associated with alcohol increased by 3.09% per year.
Several factors, such as an aging US population and increasing alcohol consumption, play a major role in the uptick in mortality, said lead author Pojsakorn Danpanichkul, MD, an internal medicine resident at Texas Tech University Health Sciences Center, Lubbock, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
“Healthcare providers should increase screening for alcohol use among older adults and consider the added risks of alcohol consumption. Public health strategies should target alcohol prevention and treatment programs tailored to older adults,” he said.
“Older adults are more vulnerable to the harmful effects of alcohol due to natural declines in liver function and metabolism, leading to a higher risk of liver disease and complications,” he explained. However, “little research has focused on this issue.”
Trends in US Not Seen Globally
Danpanichkul and colleagues analyzed data from the Global Burden of Disease Study for 2010-2019, calculating the annual percent change for the burden of AUD, ALD, and liver cancer from alcohol in patients age 70 and older. The research team then compared data in the United States to global estimates for these same diseases.
In 2019, there were 556,340 cases of AUD, 112,560 cases of ALD, and 3720 cases of liver cancer from alcohol in older adults in the United States. In addition, there were 1750 deaths attributed to AUD, 4860 deaths from ALD, and 3010 deaths caused by primary liver cancer from alcohol.
The age-standardized prevalence rates (ASPRs) per 100,000 people were 1547 cases of AUD, 313 cases of ALD, and 10 cases of primary liver cancer caused by alcohol.
The age-standardized death rates (ASDRs) per 100,000 people were 4.88 for AUD, 13.52 for ALD, and 8.38 for primary liver cancer.
During the time period studied, upward trends occurred in the United States, with annual ASPRs increasing by 2.52% for AUD, 1.78% for ALD, and 3.31% for primary liver cancer due to alcohol. Globally, the trends were lower, with annual increases of 0.2% for AUD, 0.38% for ALD, and 0.67% for primary liver cancer from alcohol.
During the same time, ASDRs also increased in all three categories in the United States, while global trends showed a 0.91% decline in AUD deaths and 0.6% decline in ALD deaths. Liver cancer deaths, however, increased by 0.3% worldwide.
Targeted strategies are essential to reduce this growing health burden, especially in an aging population, Danpanichkul said. “These interventions should focus on early detection, intervention, and management for individuals at risk or already affected by ALD and AUD.”
Future studies should investigate alcohol consumption and mortality trends in other age groups, including by sex, location (such as state or territory), and race and ethnicity, he said. Data for more recent years would be compelling as well.
Increased Alcohol Use During and After Pandemic
Numerous studies have indicated that alcohol use increased in 2020 during the COVID-19 pandemic and has remained elevated since then.
In a study published in the Annals of Internal Medicine, for instance, alcohol use per 100 people increased 2.69% in 2020 and 2.96% in 2022, as compared with 2018. Increases occurred across all subgroups, including age, sex, race, ethnicity, and US region.
“During the COVID-19 pandemic, many people stayed at home, watched the television, and increased their alcohol intake” — in the United States and also in Japan — said Hisanori Muto, MD, senior assistant professor of gastroenterology at Fujita Health University in Nagoya, Japan, who wasn’t involved with this study.
“Although the global numbers may appear lower, we’re also seeing an increase in AUD and ALD in Japan, similar to the United States,” he said. “It’s very important to watch these trends and address these diseases.”
Danpanichkul and Muto reported no relevant disclosures.
A version of this article appeared on Medscape.com.
SAN DIEGO — according to the results of a new study.
Even as mortality rates decline globally, AUD deaths rose in the United States, increasing 1.63% per year between 2010 and 2019. Deaths from cirrhosis increased by 0.56% each year, and deaths from primary liver cancer associated with alcohol increased by 3.09% per year.
Several factors, such as an aging US population and increasing alcohol consumption, play a major role in the uptick in mortality, said lead author Pojsakorn Danpanichkul, MD, an internal medicine resident at Texas Tech University Health Sciences Center, Lubbock, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
“Healthcare providers should increase screening for alcohol use among older adults and consider the added risks of alcohol consumption. Public health strategies should target alcohol prevention and treatment programs tailored to older adults,” he said.
“Older adults are more vulnerable to the harmful effects of alcohol due to natural declines in liver function and metabolism, leading to a higher risk of liver disease and complications,” he explained. However, “little research has focused on this issue.”
Trends in US Not Seen Globally
Danpanichkul and colleagues analyzed data from the Global Burden of Disease Study for 2010-2019, calculating the annual percent change for the burden of AUD, ALD, and liver cancer from alcohol in patients age 70 and older. The research team then compared data in the United States to global estimates for these same diseases.
In 2019, there were 556,340 cases of AUD, 112,560 cases of ALD, and 3720 cases of liver cancer from alcohol in older adults in the United States. In addition, there were 1750 deaths attributed to AUD, 4860 deaths from ALD, and 3010 deaths caused by primary liver cancer from alcohol.
The age-standardized prevalence rates (ASPRs) per 100,000 people were 1547 cases of AUD, 313 cases of ALD, and 10 cases of primary liver cancer caused by alcohol.
The age-standardized death rates (ASDRs) per 100,000 people were 4.88 for AUD, 13.52 for ALD, and 8.38 for primary liver cancer.
During the time period studied, upward trends occurred in the United States, with annual ASPRs increasing by 2.52% for AUD, 1.78% for ALD, and 3.31% for primary liver cancer due to alcohol. Globally, the trends were lower, with annual increases of 0.2% for AUD, 0.38% for ALD, and 0.67% for primary liver cancer from alcohol.
During the same time, ASDRs also increased in all three categories in the United States, while global trends showed a 0.91% decline in AUD deaths and 0.6% decline in ALD deaths. Liver cancer deaths, however, increased by 0.3% worldwide.
Targeted strategies are essential to reduce this growing health burden, especially in an aging population, Danpanichkul said. “These interventions should focus on early detection, intervention, and management for individuals at risk or already affected by ALD and AUD.”
Future studies should investigate alcohol consumption and mortality trends in other age groups, including by sex, location (such as state or territory), and race and ethnicity, he said. Data for more recent years would be compelling as well.
Increased Alcohol Use During and After Pandemic
Numerous studies have indicated that alcohol use increased in 2020 during the COVID-19 pandemic and has remained elevated since then.
In a study published in the Annals of Internal Medicine, for instance, alcohol use per 100 people increased 2.69% in 2020 and 2.96% in 2022, as compared with 2018. Increases occurred across all subgroups, including age, sex, race, ethnicity, and US region.
“During the COVID-19 pandemic, many people stayed at home, watched the television, and increased their alcohol intake” — in the United States and also in Japan — said Hisanori Muto, MD, senior assistant professor of gastroenterology at Fujita Health University in Nagoya, Japan, who wasn’t involved with this study.
“Although the global numbers may appear lower, we’re also seeing an increase in AUD and ALD in Japan, similar to the United States,” he said. “It’s very important to watch these trends and address these diseases.”
Danpanichkul and Muto reported no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM AASLD 2024
Alcohol Use Disorder Therapy Remains Underutilized in Alcohol-Associated Liver Disease
PHILADELPHIA — according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.
In an analysis of commercially insured Americans, AUD medications were prescribed to only 1 in 50 patients with ALD and about 1 in 10 patients with acute alcohol-associated hepatitis (AAH).
“Providers caring for these patients should consider early initiation of this therapy in select cases,” said lead author Alex R. Jones, MD, chief resident of internal medicine at the University of Texas Southwestern Medical Center in Dallas.
“Based on additional analyses looking at the prescriber subspecialty, we didn’t identify any gastroenterologists or hepatologists who prescribed pharmacotherapy,” he said. “This could be a great opportunity for hepatologists to engage in the pharmacologic treatment of AUD.”
Jones and colleagues analyzed 2006-2021 data from IQVIA PharMetrics Plus for Academics, a nationally representative database of commercially insured patients in the United States. They looked for AUD pharmacologic treatment at any time after AUD diagnosis, including prescriptions for gabapentin, naltrexone, topiramate, acamprosate, baclofen, and disulfiram.
Among 28,625 patients with AUD (defined as at least two outpatient codes or at least one inpatient code), 1201 had ALD with cirrhosis and 439 had AAH.
Pharmacologic therapy was prescribed in 3924 (14.5%) patients without ALD, 28 (2.3%) with ALD, and 42 (9.8%) with AAH.
In addition, one-time prescriptions were observed in 1113 (28.4%) patients without ALD, three patients (10.7%) with ALD, and eight patients (18.6%) with AAH.
Overall, 64.5% of the general population consisted of men. About 46% had a psychiatric diagnosis other than substance use disorder (SUD), and 35.7% had a non-AUD SUD.
Patients who received AUD pharmacotherapy tended to be older, at a median age of 45 years, than those aged 42 years without a prescription.
The median time to prescription was 302 days, with no significant differences based on the presence of liver disease.
By medication, gabapentin was prescribed most often (9.4%), followed by oral naltrexone (2.6%) and topiramate (2%). Oral naltrexone was prescribed at a lower rate in patients with ALD and at a higher rate in patients with AAH than in patients without ALD. Baclofen was also prescribed at lower rates in patients with ALD and AAH.
In a multivariable logistic regression analysis, several characteristics were more significantly associated with pharmacologic therapy, such as age ≥ 50 years (adjusted odds ratio [aOR], 1.33), female sex (aOR, 1.31), a non-liver Charlson Comorbidity Index ≥ 3 (aOR, 2.21), and psychiatric comorbidities (aOR, 2.76).
On the other hand, the presence of hepatic decompensation — defined as ascites, hepatic encephalopathy, or bleeding varices — was associated with lower odds of receiving pharmacotherapy (aOR, 0.08). ALD cirrhosis (non-AAH) also had lower odds (aOR, 0.24).
The study was limited by only incorporating patients with commercial insurance, lacking demographic details related to race or ethnicity, and potentially misclassifying patients despite validated definitions of ALD and AUD, Jones said.
As the study couldn’t determine the indications for prescriptions, such as gabapentin use for migraines or diabetes-associated neuropathy, for instance, future studies could look at these precise details, he added.
“It’s important to know we’re underutilizing therapies that we have a lot of information about, such as gabapentin, which is an old medication that we should feel fairly comfortable using,” said Patricia Jones, MD, a hepatologist and associate professor of clinical medicine at the University of Miami Miller School of Medicine, in Florida. Patricia Jones comoderated the plenary session on small intestine, functional, and liver research.
“I also expect that, if a future study reviewed this data and excluded people with valid indications, such as migraines or diabetic neuropathy, we’d see even lower rates of prescription,” she said.
From a clinical perspective, patient communication and clinical decision-making are key, Patricia Jones added, particularly when clinical gastroenterologists and hepatologists may not offer this type of therapy or patients refuse this type of therapy.
“We need to think about our practice patterns and how we can offer therapy,” she said. “In general, we know these medications are very safe. Even though they’re not widely used in people with cirrhosis, there’s not enough evidence to suggest we shouldn’t use them.”
Alex Jones and Patricia Jones reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
PHILADELPHIA — according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.
In an analysis of commercially insured Americans, AUD medications were prescribed to only 1 in 50 patients with ALD and about 1 in 10 patients with acute alcohol-associated hepatitis (AAH).
“Providers caring for these patients should consider early initiation of this therapy in select cases,” said lead author Alex R. Jones, MD, chief resident of internal medicine at the University of Texas Southwestern Medical Center in Dallas.
“Based on additional analyses looking at the prescriber subspecialty, we didn’t identify any gastroenterologists or hepatologists who prescribed pharmacotherapy,” he said. “This could be a great opportunity for hepatologists to engage in the pharmacologic treatment of AUD.”
Jones and colleagues analyzed 2006-2021 data from IQVIA PharMetrics Plus for Academics, a nationally representative database of commercially insured patients in the United States. They looked for AUD pharmacologic treatment at any time after AUD diagnosis, including prescriptions for gabapentin, naltrexone, topiramate, acamprosate, baclofen, and disulfiram.
Among 28,625 patients with AUD (defined as at least two outpatient codes or at least one inpatient code), 1201 had ALD with cirrhosis and 439 had AAH.
Pharmacologic therapy was prescribed in 3924 (14.5%) patients without ALD, 28 (2.3%) with ALD, and 42 (9.8%) with AAH.
In addition, one-time prescriptions were observed in 1113 (28.4%) patients without ALD, three patients (10.7%) with ALD, and eight patients (18.6%) with AAH.
Overall, 64.5% of the general population consisted of men. About 46% had a psychiatric diagnosis other than substance use disorder (SUD), and 35.7% had a non-AUD SUD.
Patients who received AUD pharmacotherapy tended to be older, at a median age of 45 years, than those aged 42 years without a prescription.
The median time to prescription was 302 days, with no significant differences based on the presence of liver disease.
By medication, gabapentin was prescribed most often (9.4%), followed by oral naltrexone (2.6%) and topiramate (2%). Oral naltrexone was prescribed at a lower rate in patients with ALD and at a higher rate in patients with AAH than in patients without ALD. Baclofen was also prescribed at lower rates in patients with ALD and AAH.
In a multivariable logistic regression analysis, several characteristics were more significantly associated with pharmacologic therapy, such as age ≥ 50 years (adjusted odds ratio [aOR], 1.33), female sex (aOR, 1.31), a non-liver Charlson Comorbidity Index ≥ 3 (aOR, 2.21), and psychiatric comorbidities (aOR, 2.76).
On the other hand, the presence of hepatic decompensation — defined as ascites, hepatic encephalopathy, or bleeding varices — was associated with lower odds of receiving pharmacotherapy (aOR, 0.08). ALD cirrhosis (non-AAH) also had lower odds (aOR, 0.24).
The study was limited by only incorporating patients with commercial insurance, lacking demographic details related to race or ethnicity, and potentially misclassifying patients despite validated definitions of ALD and AUD, Jones said.
As the study couldn’t determine the indications for prescriptions, such as gabapentin use for migraines or diabetes-associated neuropathy, for instance, future studies could look at these precise details, he added.
“It’s important to know we’re underutilizing therapies that we have a lot of information about, such as gabapentin, which is an old medication that we should feel fairly comfortable using,” said Patricia Jones, MD, a hepatologist and associate professor of clinical medicine at the University of Miami Miller School of Medicine, in Florida. Patricia Jones comoderated the plenary session on small intestine, functional, and liver research.
“I also expect that, if a future study reviewed this data and excluded people with valid indications, such as migraines or diabetic neuropathy, we’d see even lower rates of prescription,” she said.
From a clinical perspective, patient communication and clinical decision-making are key, Patricia Jones added, particularly when clinical gastroenterologists and hepatologists may not offer this type of therapy or patients refuse this type of therapy.
“We need to think about our practice patterns and how we can offer therapy,” she said. “In general, we know these medications are very safe. Even though they’re not widely used in people with cirrhosis, there’s not enough evidence to suggest we shouldn’t use them.”
Alex Jones and Patricia Jones reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
PHILADELPHIA — according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.
In an analysis of commercially insured Americans, AUD medications were prescribed to only 1 in 50 patients with ALD and about 1 in 10 patients with acute alcohol-associated hepatitis (AAH).
“Providers caring for these patients should consider early initiation of this therapy in select cases,” said lead author Alex R. Jones, MD, chief resident of internal medicine at the University of Texas Southwestern Medical Center in Dallas.
“Based on additional analyses looking at the prescriber subspecialty, we didn’t identify any gastroenterologists or hepatologists who prescribed pharmacotherapy,” he said. “This could be a great opportunity for hepatologists to engage in the pharmacologic treatment of AUD.”
Jones and colleagues analyzed 2006-2021 data from IQVIA PharMetrics Plus for Academics, a nationally representative database of commercially insured patients in the United States. They looked for AUD pharmacologic treatment at any time after AUD diagnosis, including prescriptions for gabapentin, naltrexone, topiramate, acamprosate, baclofen, and disulfiram.
Among 28,625 patients with AUD (defined as at least two outpatient codes or at least one inpatient code), 1201 had ALD with cirrhosis and 439 had AAH.
Pharmacologic therapy was prescribed in 3924 (14.5%) patients without ALD, 28 (2.3%) with ALD, and 42 (9.8%) with AAH.
In addition, one-time prescriptions were observed in 1113 (28.4%) patients without ALD, three patients (10.7%) with ALD, and eight patients (18.6%) with AAH.
Overall, 64.5% of the general population consisted of men. About 46% had a psychiatric diagnosis other than substance use disorder (SUD), and 35.7% had a non-AUD SUD.
Patients who received AUD pharmacotherapy tended to be older, at a median age of 45 years, than those aged 42 years without a prescription.
The median time to prescription was 302 days, with no significant differences based on the presence of liver disease.
By medication, gabapentin was prescribed most often (9.4%), followed by oral naltrexone (2.6%) and topiramate (2%). Oral naltrexone was prescribed at a lower rate in patients with ALD and at a higher rate in patients with AAH than in patients without ALD. Baclofen was also prescribed at lower rates in patients with ALD and AAH.
In a multivariable logistic regression analysis, several characteristics were more significantly associated with pharmacologic therapy, such as age ≥ 50 years (adjusted odds ratio [aOR], 1.33), female sex (aOR, 1.31), a non-liver Charlson Comorbidity Index ≥ 3 (aOR, 2.21), and psychiatric comorbidities (aOR, 2.76).
On the other hand, the presence of hepatic decompensation — defined as ascites, hepatic encephalopathy, or bleeding varices — was associated with lower odds of receiving pharmacotherapy (aOR, 0.08). ALD cirrhosis (non-AAH) also had lower odds (aOR, 0.24).
The study was limited by only incorporating patients with commercial insurance, lacking demographic details related to race or ethnicity, and potentially misclassifying patients despite validated definitions of ALD and AUD, Jones said.
As the study couldn’t determine the indications for prescriptions, such as gabapentin use for migraines or diabetes-associated neuropathy, for instance, future studies could look at these precise details, he added.
“It’s important to know we’re underutilizing therapies that we have a lot of information about, such as gabapentin, which is an old medication that we should feel fairly comfortable using,” said Patricia Jones, MD, a hepatologist and associate professor of clinical medicine at the University of Miami Miller School of Medicine, in Florida. Patricia Jones comoderated the plenary session on small intestine, functional, and liver research.
“I also expect that, if a future study reviewed this data and excluded people with valid indications, such as migraines or diabetic neuropathy, we’d see even lower rates of prescription,” she said.
From a clinical perspective, patient communication and clinical decision-making are key, Patricia Jones added, particularly when clinical gastroenterologists and hepatologists may not offer this type of therapy or patients refuse this type of therapy.
“We need to think about our practice patterns and how we can offer therapy,” she said. “In general, we know these medications are very safe. Even though they’re not widely used in people with cirrhosis, there’s not enough evidence to suggest we shouldn’t use them.”
Alex Jones and Patricia Jones reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM ACG 2024
Promising New Data for Drugs Both Novel and Established in Several Common GI Conditions
I’ve just returned from the annual meeting of the American College of Gastroenterology (ACG), which was held in Philadelphia, Pennsylvania.
Repetitive Use Injuries Among Endoscopists
First is a study that assessed musculoskeletal injuries that occurred while performing endoscopy, which is a large part of what we do as gastroenterologists. I’ve personally experienced virtually all these injuries during my 45-plus years in the field. These findings provide a useful perspective of what we can do to potentially avoid such injuries going forward.
This study comes to us from researchers at the University of Utah, who looked at an author-developed and validated questionnaire called QuickDash (Disability of Arm, Shoulder, Hand). Endoscopists were evaluated by occupational therapists in their department, who looked at strength testing as well as a series of provocative tests to identify injuries.
Thirty-five endoscopists were enrolled. Overall, 34% reported experiencing pain and 17% reported numbness. In the previous week, 48% had been bothered by pain and 11% by tingling, and 17% reported limitations on what they could do at work.
Additionally, 17% experienced interrupted sleep. I think that finding is particularly important, because when you have fragmented sleep it lowers sensory thresholds. Essentially, this means that the day after interrupted sleep, you respond with a heightened sensory response.
Physical testing showed reduction in grip strength in approximately half of participants, including both right and left grip. More than 70% had at least one abnormal positive provocative test.
There were a couple factors associated with an increased risk for adverse outcomes. Those who performed 20 or more procedures a week were at higher risk of pain (P = .007). I recognize that some of you probably perform 20 or more endoscopies in a single day.
Negative outcomes were also more likely to occur among physicians performing biliary endoscopy. Performing endoscopic retrograde cholangiopancreatography during 20%-60% of the week resulted in greater likelihood of experiencing decreased bilateral pinch strength.
The bottom line is that there’s an extremely high prevalence of repetitive use injury among endoscopists. Whether you’re just starting out, mid-career, or more senior, you need to be aware of this.
Kudos to the ACG who put together hands-on sessions across 2 days with extended ergonomics training provided by physical therapists with expertise in this area. These sessions were standing room only every time I visited them.
During the meeting, the ACG also announced the publication of a new book, Ergonomics for Endoscopy: Optimal Preparation, Performance, and Recovery, that is available on the ACG’s website. I had the privilege to meet the two authors, survey the book, and briefly discuss it with them. It’s phenomenal, and something that I think every endoscopist can benefit from.
So, in summary, don’t put aside these concerns. It’s your career, and the better we can do in preventing these injuries, I think the better you’ll feel going forward.
On-Demand Vonoprazan for Heartburn
The second study of note dealt with vonoprazan, a potassium-competitive acid blocker.
The question surrounding vonoprazan is whether it has clinical value as an on-demand option rather than simply as maintenance therapy administered via daily dosing. Previous results have suggested that it may have a more rapid effect when it’s taken on demand.
This post hoc analysis of a randomized trial evaluated a 4-week run-in period during which patients received vonoprazan 20 mg daily, followed by a 6-week period after which patients switched to on-demand therapy. To be eligible, during the run-in period patients had to be 80% compliant with the study drug and report no heartburn during the last 7 days of treatment. If so, they were then randomized to receive vonoprazan at 10 mg, 20 mg, or 40 mg, or placebo.
Eligible patients reported 16% heartburn-free days during the screening period. During the run-in period, heartburn-free days increased to 83% among those taking vonoprazan 20 mg daily. When this was stopped and patients transitioned to on-demand vonoprazan, they still had a very high rate of heartburn-free days, ranging from 71% to 75%. Over 90% in the treatment group had their symptoms improved within 2 hours, with improvement noted as early as within 1 hour.
We know that proton pump inhibitors don’t produce this effect, which presents a challenge for us. This study suggests there may be a very strong role for on-demand therapy in patients who have reflux, which certainly showed in terms of responsiveness during the 4-week run-in period.
Rifaximin Monotherapy Reduces Risk for Overt Hepatic Encephalopathy Recurrence
The next trial looked at rifaximin monotherapy for prevention of relapse of overt hepatic encephalopathy.
Rifaximin has been added to the baseline primary treatment of lactulose, a combination that has been analyzed in pivotal studies. However, lactulose is a difficult drug to titrate. We typically ask patients to let us know if they have Bristol Stool Scale scores ≥ 6. This results in an inordinate number of calls back to the clinic or office. Diarrhea is a particular problem in these patients.
This study, which was presented by Dr Jasmohan S. Bajaj from Virginia Commonwealth University, analyzed data from two randomized trials: a phase 3, double-blind trial and a phase 4 open-label trial. Both studies were conducted in patients with Child-Pugh classification A and B cirrhosis, whose overt hepatic encephalopathy was graded with a Conn score ≤ 1. Researchers only looked at those patients who received rifaximin 550 mg twice daily without lactulose, or lactulose titrated to a target of two to three soft stools a day plus placebo. The primary endpoint, which was used in both trials, was time to first breakthrough overt hepatic encephalopathy episode, measured as a Conn score ≥ 2.
There were 125 patients in the rifaximin group and 145 patients in the lactulose group. Patients in both groups had mean age of 57 years and a median Model for End-Stage Liver Disease score of 12.
Treatment with rifaximin produced significantly striking results. In the rifaximin group, the risk for breakthrough overt hepatic encephalopathy episodes was reduced by 60%, with a number needed to treat of 4, which is extremely powerful. Regarding mortality reduction, the number needed to treat with rifaximin alone was 19.
The take-away message here is that it’s difficult to use lactulose. We frequently have to stop it. These results provide reassurance that rifaximin has a dramatic effect even when used by itself. The recommended first-line therapy is still to begin with lactulose, but this study provides us with very strong data regarding the use of rifaximin alone.
Apraglutide’s Efficacy in Short-Bowel Syndrome
The fourth study I’d like to highlight adds to the growing data around a long-acting glucagon-like peptide 2 analog, apraglutide.
Results from the phase 3, double-blind STARS trial were first presented at Digestive Disease Week earlier in the year. They showed that apraglutide had efficacy and contributed to a reduction in the risk for needing parenteral support, maintenance of weight, and fluid requirements in patients with short-bowel syndrome and intestinal failure. However, questions remained regarding whether there were variations in response based on patient demographics and short-bowel syndrome–specific characteristics.
Researchers looked at a subgroup of patients from the STARS trial. The primary endpoint remained the same as in the main trial: relative change from baseline in actual parenteral support weekly volume at week 24. However, rather than measure it in the overall population, they did so according to geographic region, gender, age, body weight, race and ethnicity, and short-bowel syndrome characteristics, including differences in parenteral support volume, length of the remnant small intestine, and time from short-bowel syndrome diagnosis.
Across all these demographic and disease characteristic categories, there was absolutely no difference in the primary endpoint.
Apraglutide seems to be inordinately promising. This is a once-weekly treatment, as opposed to liraglutide, which is problematic because it has to be given daily.
From what I understand, apraglutide has been offered a fast-track status by the US Food and Drug Administration. Again, from what I’ve heard, it will be evaluated upon submission beginning sometime in the first quarter of 2025, which may mean that apraglutide could be available as early as 2026.
This would be a big deal for patients with short-bowel syndrome who would have a once-weekly treatment option as opposed to daily treatment and its accompanying problems of compliance and relatively reduced response.
Biologics for Treating Immune Checkpoint Inhibitor Colitis
The final study I want to discuss in this presentation dealt with adverse responses to immune checkpoint inhibitor (ICI) therapy. We see this increasingly in our clinics as ICIs become more widely used. They are wonderful drugs, but ICI-induced colitis can occur in up to 30% of patients.
The oncologic approach is to try and stay the course, while gastroenterologists are tasked with treating the colitis so that these patients can maintain their cancer treatment. Steroid therapy is the primary first-line treatment against ICI colitis, but the use of biologic therapy with infliximab or vedolizumab has been associated with favorable outcomes as well.
ICI colitis is graded on a scale. Whereas grade 1 ICI colitis indicates increased stool frequency of less than four a day and the absence of symptoms, grade 2 indicates a progression to a stool frequency of four to six times a day, the appearance of blood or mucus in the stool, and symptoms like abdominal pain.
Researchers sought to answer the question of which treatment is better for patients with moderate to severe ICI colitis: infliximab or vedolizumab? They performed a database analysis of patients at their institution who received at least one dose of these biologics. The endpoint was sustained clinical response (ie, without a recurrent colitis episode), as well as patients achieving improvement to grade 1 ICI colitis.
The data for infliximab and vedolizumab were quite good. Sustained clinical response was noted in 91% of patients receiving infliximab and 86% receiving vedolizumab. There was no difference in infection risk between the groups.
There’s a teaching point in the study’s other key finding, which is that following biologic initiation, steroids were more rapidly discontinued with vedolizumab vs infliximab (median, 25 days vs 56 days, respectively). Therefore, vedolizumab may have the added benefit of patients being able to get off steroids more quickly. That’s the take-home message: Vedolizumab may be better. We certainly are comfortable with both biologics, but patients getting off steroids would be better.
There are two additional teaching points I’d like to convey.
First, don’t forget to perform a biopsy, because there are patients who may have cytomegalovirus colitis and we don’t want to miss it. A biopsy may also reveal whether they have a macroscopically normal rectosigmoid. So, you should biopsy to look for microscopic changes. As 98% of ICI colitis cases involve the left colon, you can get by with just using a flexible sigmoidoscopy.
Second, don’t forget to check for celiac disease. Patients taking ICIs may develop celiac disease as a side effect of treatment. So, I always order a celiac profile as well.
These are, in my opinion, five of the top studies from ACG 2024, with the remaining studies to be discussed in my next video. They all provide opportunities to help us improve our patients’ health.
Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He reported serving in an advisory position with ISOTHRIVE. This transcript has been edited for clarity.
A version of this article appeared on Medscape.com.
I’ve just returned from the annual meeting of the American College of Gastroenterology (ACG), which was held in Philadelphia, Pennsylvania.
Repetitive Use Injuries Among Endoscopists
First is a study that assessed musculoskeletal injuries that occurred while performing endoscopy, which is a large part of what we do as gastroenterologists. I’ve personally experienced virtually all these injuries during my 45-plus years in the field. These findings provide a useful perspective of what we can do to potentially avoid such injuries going forward.
This study comes to us from researchers at the University of Utah, who looked at an author-developed and validated questionnaire called QuickDash (Disability of Arm, Shoulder, Hand). Endoscopists were evaluated by occupational therapists in their department, who looked at strength testing as well as a series of provocative tests to identify injuries.
Thirty-five endoscopists were enrolled. Overall, 34% reported experiencing pain and 17% reported numbness. In the previous week, 48% had been bothered by pain and 11% by tingling, and 17% reported limitations on what they could do at work.
Additionally, 17% experienced interrupted sleep. I think that finding is particularly important, because when you have fragmented sleep it lowers sensory thresholds. Essentially, this means that the day after interrupted sleep, you respond with a heightened sensory response.
Physical testing showed reduction in grip strength in approximately half of participants, including both right and left grip. More than 70% had at least one abnormal positive provocative test.
There were a couple factors associated with an increased risk for adverse outcomes. Those who performed 20 or more procedures a week were at higher risk of pain (P = .007). I recognize that some of you probably perform 20 or more endoscopies in a single day.
Negative outcomes were also more likely to occur among physicians performing biliary endoscopy. Performing endoscopic retrograde cholangiopancreatography during 20%-60% of the week resulted in greater likelihood of experiencing decreased bilateral pinch strength.
The bottom line is that there’s an extremely high prevalence of repetitive use injury among endoscopists. Whether you’re just starting out, mid-career, or more senior, you need to be aware of this.
Kudos to the ACG who put together hands-on sessions across 2 days with extended ergonomics training provided by physical therapists with expertise in this area. These sessions were standing room only every time I visited them.
During the meeting, the ACG also announced the publication of a new book, Ergonomics for Endoscopy: Optimal Preparation, Performance, and Recovery, that is available on the ACG’s website. I had the privilege to meet the two authors, survey the book, and briefly discuss it with them. It’s phenomenal, and something that I think every endoscopist can benefit from.
So, in summary, don’t put aside these concerns. It’s your career, and the better we can do in preventing these injuries, I think the better you’ll feel going forward.
On-Demand Vonoprazan for Heartburn
The second study of note dealt with vonoprazan, a potassium-competitive acid blocker.
The question surrounding vonoprazan is whether it has clinical value as an on-demand option rather than simply as maintenance therapy administered via daily dosing. Previous results have suggested that it may have a more rapid effect when it’s taken on demand.
This post hoc analysis of a randomized trial evaluated a 4-week run-in period during which patients received vonoprazan 20 mg daily, followed by a 6-week period after which patients switched to on-demand therapy. To be eligible, during the run-in period patients had to be 80% compliant with the study drug and report no heartburn during the last 7 days of treatment. If so, they were then randomized to receive vonoprazan at 10 mg, 20 mg, or 40 mg, or placebo.
Eligible patients reported 16% heartburn-free days during the screening period. During the run-in period, heartburn-free days increased to 83% among those taking vonoprazan 20 mg daily. When this was stopped and patients transitioned to on-demand vonoprazan, they still had a very high rate of heartburn-free days, ranging from 71% to 75%. Over 90% in the treatment group had their symptoms improved within 2 hours, with improvement noted as early as within 1 hour.
We know that proton pump inhibitors don’t produce this effect, which presents a challenge for us. This study suggests there may be a very strong role for on-demand therapy in patients who have reflux, which certainly showed in terms of responsiveness during the 4-week run-in period.
Rifaximin Monotherapy Reduces Risk for Overt Hepatic Encephalopathy Recurrence
The next trial looked at rifaximin monotherapy for prevention of relapse of overt hepatic encephalopathy.
Rifaximin has been added to the baseline primary treatment of lactulose, a combination that has been analyzed in pivotal studies. However, lactulose is a difficult drug to titrate. We typically ask patients to let us know if they have Bristol Stool Scale scores ≥ 6. This results in an inordinate number of calls back to the clinic or office. Diarrhea is a particular problem in these patients.
This study, which was presented by Dr Jasmohan S. Bajaj from Virginia Commonwealth University, analyzed data from two randomized trials: a phase 3, double-blind trial and a phase 4 open-label trial. Both studies were conducted in patients with Child-Pugh classification A and B cirrhosis, whose overt hepatic encephalopathy was graded with a Conn score ≤ 1. Researchers only looked at those patients who received rifaximin 550 mg twice daily without lactulose, or lactulose titrated to a target of two to three soft stools a day plus placebo. The primary endpoint, which was used in both trials, was time to first breakthrough overt hepatic encephalopathy episode, measured as a Conn score ≥ 2.
There were 125 patients in the rifaximin group and 145 patients in the lactulose group. Patients in both groups had mean age of 57 years and a median Model for End-Stage Liver Disease score of 12.
Treatment with rifaximin produced significantly striking results. In the rifaximin group, the risk for breakthrough overt hepatic encephalopathy episodes was reduced by 60%, with a number needed to treat of 4, which is extremely powerful. Regarding mortality reduction, the number needed to treat with rifaximin alone was 19.
The take-away message here is that it’s difficult to use lactulose. We frequently have to stop it. These results provide reassurance that rifaximin has a dramatic effect even when used by itself. The recommended first-line therapy is still to begin with lactulose, but this study provides us with very strong data regarding the use of rifaximin alone.
Apraglutide’s Efficacy in Short-Bowel Syndrome
The fourth study I’d like to highlight adds to the growing data around a long-acting glucagon-like peptide 2 analog, apraglutide.
Results from the phase 3, double-blind STARS trial were first presented at Digestive Disease Week earlier in the year. They showed that apraglutide had efficacy and contributed to a reduction in the risk for needing parenteral support, maintenance of weight, and fluid requirements in patients with short-bowel syndrome and intestinal failure. However, questions remained regarding whether there were variations in response based on patient demographics and short-bowel syndrome–specific characteristics.
Researchers looked at a subgroup of patients from the STARS trial. The primary endpoint remained the same as in the main trial: relative change from baseline in actual parenteral support weekly volume at week 24. However, rather than measure it in the overall population, they did so according to geographic region, gender, age, body weight, race and ethnicity, and short-bowel syndrome characteristics, including differences in parenteral support volume, length of the remnant small intestine, and time from short-bowel syndrome diagnosis.
Across all these demographic and disease characteristic categories, there was absolutely no difference in the primary endpoint.
Apraglutide seems to be inordinately promising. This is a once-weekly treatment, as opposed to liraglutide, which is problematic because it has to be given daily.
From what I understand, apraglutide has been offered a fast-track status by the US Food and Drug Administration. Again, from what I’ve heard, it will be evaluated upon submission beginning sometime in the first quarter of 2025, which may mean that apraglutide could be available as early as 2026.
This would be a big deal for patients with short-bowel syndrome who would have a once-weekly treatment option as opposed to daily treatment and its accompanying problems of compliance and relatively reduced response.
Biologics for Treating Immune Checkpoint Inhibitor Colitis
The final study I want to discuss in this presentation dealt with adverse responses to immune checkpoint inhibitor (ICI) therapy. We see this increasingly in our clinics as ICIs become more widely used. They are wonderful drugs, but ICI-induced colitis can occur in up to 30% of patients.
The oncologic approach is to try and stay the course, while gastroenterologists are tasked with treating the colitis so that these patients can maintain their cancer treatment. Steroid therapy is the primary first-line treatment against ICI colitis, but the use of biologic therapy with infliximab or vedolizumab has been associated with favorable outcomes as well.
ICI colitis is graded on a scale. Whereas grade 1 ICI colitis indicates increased stool frequency of less than four a day and the absence of symptoms, grade 2 indicates a progression to a stool frequency of four to six times a day, the appearance of blood or mucus in the stool, and symptoms like abdominal pain.
Researchers sought to answer the question of which treatment is better for patients with moderate to severe ICI colitis: infliximab or vedolizumab? They performed a database analysis of patients at their institution who received at least one dose of these biologics. The endpoint was sustained clinical response (ie, without a recurrent colitis episode), as well as patients achieving improvement to grade 1 ICI colitis.
The data for infliximab and vedolizumab were quite good. Sustained clinical response was noted in 91% of patients receiving infliximab and 86% receiving vedolizumab. There was no difference in infection risk between the groups.
There’s a teaching point in the study’s other key finding, which is that following biologic initiation, steroids were more rapidly discontinued with vedolizumab vs infliximab (median, 25 days vs 56 days, respectively). Therefore, vedolizumab may have the added benefit of patients being able to get off steroids more quickly. That’s the take-home message: Vedolizumab may be better. We certainly are comfortable with both biologics, but patients getting off steroids would be better.
There are two additional teaching points I’d like to convey.
First, don’t forget to perform a biopsy, because there are patients who may have cytomegalovirus colitis and we don’t want to miss it. A biopsy may also reveal whether they have a macroscopically normal rectosigmoid. So, you should biopsy to look for microscopic changes. As 98% of ICI colitis cases involve the left colon, you can get by with just using a flexible sigmoidoscopy.
Second, don’t forget to check for celiac disease. Patients taking ICIs may develop celiac disease as a side effect of treatment. So, I always order a celiac profile as well.
These are, in my opinion, five of the top studies from ACG 2024, with the remaining studies to be discussed in my next video. They all provide opportunities to help us improve our patients’ health.
Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He reported serving in an advisory position with ISOTHRIVE. This transcript has been edited for clarity.
A version of this article appeared on Medscape.com.
I’ve just returned from the annual meeting of the American College of Gastroenterology (ACG), which was held in Philadelphia, Pennsylvania.
Repetitive Use Injuries Among Endoscopists
First is a study that assessed musculoskeletal injuries that occurred while performing endoscopy, which is a large part of what we do as gastroenterologists. I’ve personally experienced virtually all these injuries during my 45-plus years in the field. These findings provide a useful perspective of what we can do to potentially avoid such injuries going forward.
This study comes to us from researchers at the University of Utah, who looked at an author-developed and validated questionnaire called QuickDash (Disability of Arm, Shoulder, Hand). Endoscopists were evaluated by occupational therapists in their department, who looked at strength testing as well as a series of provocative tests to identify injuries.
Thirty-five endoscopists were enrolled. Overall, 34% reported experiencing pain and 17% reported numbness. In the previous week, 48% had been bothered by pain and 11% by tingling, and 17% reported limitations on what they could do at work.
Additionally, 17% experienced interrupted sleep. I think that finding is particularly important, because when you have fragmented sleep it lowers sensory thresholds. Essentially, this means that the day after interrupted sleep, you respond with a heightened sensory response.
Physical testing showed reduction in grip strength in approximately half of participants, including both right and left grip. More than 70% had at least one abnormal positive provocative test.
There were a couple factors associated with an increased risk for adverse outcomes. Those who performed 20 or more procedures a week were at higher risk of pain (P = .007). I recognize that some of you probably perform 20 or more endoscopies in a single day.
Negative outcomes were also more likely to occur among physicians performing biliary endoscopy. Performing endoscopic retrograde cholangiopancreatography during 20%-60% of the week resulted in greater likelihood of experiencing decreased bilateral pinch strength.
The bottom line is that there’s an extremely high prevalence of repetitive use injury among endoscopists. Whether you’re just starting out, mid-career, or more senior, you need to be aware of this.
Kudos to the ACG who put together hands-on sessions across 2 days with extended ergonomics training provided by physical therapists with expertise in this area. These sessions were standing room only every time I visited them.
During the meeting, the ACG also announced the publication of a new book, Ergonomics for Endoscopy: Optimal Preparation, Performance, and Recovery, that is available on the ACG’s website. I had the privilege to meet the two authors, survey the book, and briefly discuss it with them. It’s phenomenal, and something that I think every endoscopist can benefit from.
So, in summary, don’t put aside these concerns. It’s your career, and the better we can do in preventing these injuries, I think the better you’ll feel going forward.
On-Demand Vonoprazan for Heartburn
The second study of note dealt with vonoprazan, a potassium-competitive acid blocker.
The question surrounding vonoprazan is whether it has clinical value as an on-demand option rather than simply as maintenance therapy administered via daily dosing. Previous results have suggested that it may have a more rapid effect when it’s taken on demand.
This post hoc analysis of a randomized trial evaluated a 4-week run-in period during which patients received vonoprazan 20 mg daily, followed by a 6-week period after which patients switched to on-demand therapy. To be eligible, during the run-in period patients had to be 80% compliant with the study drug and report no heartburn during the last 7 days of treatment. If so, they were then randomized to receive vonoprazan at 10 mg, 20 mg, or 40 mg, or placebo.
Eligible patients reported 16% heartburn-free days during the screening period. During the run-in period, heartburn-free days increased to 83% among those taking vonoprazan 20 mg daily. When this was stopped and patients transitioned to on-demand vonoprazan, they still had a very high rate of heartburn-free days, ranging from 71% to 75%. Over 90% in the treatment group had their symptoms improved within 2 hours, with improvement noted as early as within 1 hour.
We know that proton pump inhibitors don’t produce this effect, which presents a challenge for us. This study suggests there may be a very strong role for on-demand therapy in patients who have reflux, which certainly showed in terms of responsiveness during the 4-week run-in period.
Rifaximin Monotherapy Reduces Risk for Overt Hepatic Encephalopathy Recurrence
The next trial looked at rifaximin monotherapy for prevention of relapse of overt hepatic encephalopathy.
Rifaximin has been added to the baseline primary treatment of lactulose, a combination that has been analyzed in pivotal studies. However, lactulose is a difficult drug to titrate. We typically ask patients to let us know if they have Bristol Stool Scale scores ≥ 6. This results in an inordinate number of calls back to the clinic or office. Diarrhea is a particular problem in these patients.
This study, which was presented by Dr Jasmohan S. Bajaj from Virginia Commonwealth University, analyzed data from two randomized trials: a phase 3, double-blind trial and a phase 4 open-label trial. Both studies were conducted in patients with Child-Pugh classification A and B cirrhosis, whose overt hepatic encephalopathy was graded with a Conn score ≤ 1. Researchers only looked at those patients who received rifaximin 550 mg twice daily without lactulose, or lactulose titrated to a target of two to three soft stools a day plus placebo. The primary endpoint, which was used in both trials, was time to first breakthrough overt hepatic encephalopathy episode, measured as a Conn score ≥ 2.
There were 125 patients in the rifaximin group and 145 patients in the lactulose group. Patients in both groups had mean age of 57 years and a median Model for End-Stage Liver Disease score of 12.
Treatment with rifaximin produced significantly striking results. In the rifaximin group, the risk for breakthrough overt hepatic encephalopathy episodes was reduced by 60%, with a number needed to treat of 4, which is extremely powerful. Regarding mortality reduction, the number needed to treat with rifaximin alone was 19.
The take-away message here is that it’s difficult to use lactulose. We frequently have to stop it. These results provide reassurance that rifaximin has a dramatic effect even when used by itself. The recommended first-line therapy is still to begin with lactulose, but this study provides us with very strong data regarding the use of rifaximin alone.
Apraglutide’s Efficacy in Short-Bowel Syndrome
The fourth study I’d like to highlight adds to the growing data around a long-acting glucagon-like peptide 2 analog, apraglutide.
Results from the phase 3, double-blind STARS trial were first presented at Digestive Disease Week earlier in the year. They showed that apraglutide had efficacy and contributed to a reduction in the risk for needing parenteral support, maintenance of weight, and fluid requirements in patients with short-bowel syndrome and intestinal failure. However, questions remained regarding whether there were variations in response based on patient demographics and short-bowel syndrome–specific characteristics.
Researchers looked at a subgroup of patients from the STARS trial. The primary endpoint remained the same as in the main trial: relative change from baseline in actual parenteral support weekly volume at week 24. However, rather than measure it in the overall population, they did so according to geographic region, gender, age, body weight, race and ethnicity, and short-bowel syndrome characteristics, including differences in parenteral support volume, length of the remnant small intestine, and time from short-bowel syndrome diagnosis.
Across all these demographic and disease characteristic categories, there was absolutely no difference in the primary endpoint.
Apraglutide seems to be inordinately promising. This is a once-weekly treatment, as opposed to liraglutide, which is problematic because it has to be given daily.
From what I understand, apraglutide has been offered a fast-track status by the US Food and Drug Administration. Again, from what I’ve heard, it will be evaluated upon submission beginning sometime in the first quarter of 2025, which may mean that apraglutide could be available as early as 2026.
This would be a big deal for patients with short-bowel syndrome who would have a once-weekly treatment option as opposed to daily treatment and its accompanying problems of compliance and relatively reduced response.
Biologics for Treating Immune Checkpoint Inhibitor Colitis
The final study I want to discuss in this presentation dealt with adverse responses to immune checkpoint inhibitor (ICI) therapy. We see this increasingly in our clinics as ICIs become more widely used. They are wonderful drugs, but ICI-induced colitis can occur in up to 30% of patients.
The oncologic approach is to try and stay the course, while gastroenterologists are tasked with treating the colitis so that these patients can maintain their cancer treatment. Steroid therapy is the primary first-line treatment against ICI colitis, but the use of biologic therapy with infliximab or vedolizumab has been associated with favorable outcomes as well.
ICI colitis is graded on a scale. Whereas grade 1 ICI colitis indicates increased stool frequency of less than four a day and the absence of symptoms, grade 2 indicates a progression to a stool frequency of four to six times a day, the appearance of blood or mucus in the stool, and symptoms like abdominal pain.
Researchers sought to answer the question of which treatment is better for patients with moderate to severe ICI colitis: infliximab or vedolizumab? They performed a database analysis of patients at their institution who received at least one dose of these biologics. The endpoint was sustained clinical response (ie, without a recurrent colitis episode), as well as patients achieving improvement to grade 1 ICI colitis.
The data for infliximab and vedolizumab were quite good. Sustained clinical response was noted in 91% of patients receiving infliximab and 86% receiving vedolizumab. There was no difference in infection risk between the groups.
There’s a teaching point in the study’s other key finding, which is that following biologic initiation, steroids were more rapidly discontinued with vedolizumab vs infliximab (median, 25 days vs 56 days, respectively). Therefore, vedolizumab may have the added benefit of patients being able to get off steroids more quickly. That’s the take-home message: Vedolizumab may be better. We certainly are comfortable with both biologics, but patients getting off steroids would be better.
There are two additional teaching points I’d like to convey.
First, don’t forget to perform a biopsy, because there are patients who may have cytomegalovirus colitis and we don’t want to miss it. A biopsy may also reveal whether they have a macroscopically normal rectosigmoid. So, you should biopsy to look for microscopic changes. As 98% of ICI colitis cases involve the left colon, you can get by with just using a flexible sigmoidoscopy.
Second, don’t forget to check for celiac disease. Patients taking ICIs may develop celiac disease as a side effect of treatment. So, I always order a celiac profile as well.
These are, in my opinion, five of the top studies from ACG 2024, with the remaining studies to be discussed in my next video. They all provide opportunities to help us improve our patients’ health.
Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He reported serving in an advisory position with ISOTHRIVE. This transcript has been edited for clarity.
A version of this article appeared on Medscape.com.