Liver Disease

Large-scale scanning of serum proteins offers a potential method for noninvasive screening and monitoring of patients with nonalcoholic steatohepatitis (NASH), the technique’s developers claim.

By scanning for about 5,000 proteins in nearly 3,000 samples from patients enrolled in studies from the Clinical Research Network in NASH (NASH CRN), Rachel Ostroff, PhD, and colleagues from SomaLogic in Boulder, Colo., created four protein models that mimic results of the major pathologic findings in liver tissue biopsy.

“Concurrent positive results from the protein models had performance characteristics of ‘rule-out’ tests for pathologists’ diagnosis of NASH. These tests may assist in new drug development and medical intervention decisions,” they wrote in a late-breaking poster presented at the virtual annual meeting of the American Association for the Study of Liver Diseases.

“There is no single noninvasive method that can accurately and simultaneously capture steatosis, inflammation, hepatocyte ballooning and fibrosis, the four major pathologic components assessed by biopsy. Each of these is relevant to the multiple mechanisms targeted in drug development for NASH,” they wrote.

To see whether large-scale protemoics could serve as an alternative to invasive liver biopsy for use in clinical trials or in longitudinal studies of NASH, they used a modified aptamer proteomics platform to scan for liver-related proteins. Aptamers are olignonucleotide or peptide molecules designed to home in on a specific target.

They scanned for approximately 5,000 proteins in 2,852 serum samples from 638 patients in a NASH CRN natural history cohort, and in patients enrolled in two NASH treatment trials: the PIVENS trial, which is evaluating pioglitazone versus vitamin E and placebo in nondiabetic patients, and the FLINT trial, which is comparing obeticholic acid with placebo. All of the patients in the natural history cohort and half of all patients in the clinical trial cohorts were included in the training sets, with the remaining half included in the validation set.

The accuracy of the models, as measured by the area under the curve (AUC) of receiver operating characteristics in the training and validation sets, respectively, were as follows:

• Fibrosis: AUC 0.92/0.85.
• Steatosis: AUC 0.95/0.79.
• Inflammation: AUC 0.83/0.72.
• Hepatocyte Ballooning: AUC 0.87/0.83.

“A concurrent positive score for steatosis, inflammation and ballooning predicted the biopsy diagnosis of NASH with an accuracy of 73%,” Ostroff and colleagues wrote.

They also found that model scores applied over time showed improvements in symptoms in the patients on active therapies in the clinical trials, compared with patients on placebo.

A specialist in liver pathology and nonalcoholic fatty liver disease who was not involved in the study said in an interview that she finds the results highly promising.
 

Impressive results

Elizabeth M. Brunt, MD, emeritus professor of pathology and immunology at Washington University in St. Louis, was a member of the NASH CRN when SomaLogic first proposed using the groups’ data for this study.

“I was impressed with them then, and I am very impressed with what they’re presenting here, and I can’t say that about all the noninvasive tests,” she said. “I think a lot of noninvasive tests are way over-simplifying what NASH is.”

She acknowledged that, although she spent much of her career performing liver biopsies, “you can’t biopsy every single patients who you suspect of having NASH, or certainly if you want to follow them over time – it’s unrealistic,” she said in an interview.

Although the protein scanning method cannot – and is not intended to – replace a well-conducted biopsy with the interpretation of a skilled pathologist, the proteins the company investigators identified can reflect the dynamic nature of liver disease and the liver’s ability to heal itself with a high degree of accuracy and hold promise for both screening patients and for monitoring responses to therapy, Dr. Brunt said.

The study was sponsored by SomaLogic. The authors are employees of the company. Dr. Brunt had no relevant disclosures.

SOURCE: Ostroff R et al. The Liver Disease Meeting Digital Experience, Abstract LP11

Large-scale scanning of serum proteins offers a potential method for noninvasive screening and monitoring of patients with nonalcoholic steatohepatitis (NASH), the technique’s developers claim.

By scanning for about 5,000 proteins in nearly 3,000 samples from patients enrolled in studies from the Clinical Research Network in NASH (NASH CRN), Rachel Ostroff, PhD, and colleagues from SomaLogic in Boulder, Colo., created four protein models that mimic results of the major pathologic findings in liver tissue biopsy.

“Concurrent positive results from the protein models had performance characteristics of ‘rule-out’ tests for pathologists’ diagnosis of NASH. These tests may assist in new drug development and medical intervention decisions,” they wrote in a late-breaking poster presented at the virtual annual meeting of the American Association for the Study of Liver Diseases.

“There is no single noninvasive method that can accurately and simultaneously capture steatosis, inflammation, hepatocyte ballooning and fibrosis, the four major pathologic components assessed by biopsy. Each of these is relevant to the multiple mechanisms targeted in drug development for NASH,” they wrote.

To see whether large-scale protemoics could serve as an alternative to invasive liver biopsy for use in clinical trials or in longitudinal studies of NASH, they used a modified aptamer proteomics platform to scan for liver-related proteins. Aptamers are olignonucleotide or peptide molecules designed to home in on a specific target.

They scanned for approximately 5,000 proteins in 2,852 serum samples from 638 patients in a NASH CRN natural history cohort, and in patients enrolled in two NASH treatment trials: the PIVENS trial, which is evaluating pioglitazone versus vitamin E and placebo in nondiabetic patients, and the FLINT trial, which is comparing obeticholic acid with placebo. All of the patients in the natural history cohort and half of all patients in the clinical trial cohorts were included in the training sets, with the remaining half included in the validation set.

The accuracy of the models, as measured by the area under the curve (AUC) of receiver operating characteristics in the training and validation sets, respectively, were as follows:

• Fibrosis: AUC 0.92/0.85.
• Steatosis: AUC 0.95/0.79.
• Inflammation: AUC 0.83/0.72.
• Hepatocyte Ballooning: AUC 0.87/0.83.

“A concurrent positive score for steatosis, inflammation and ballooning predicted the biopsy diagnosis of NASH with an accuracy of 73%,” Ostroff and colleagues wrote.

They also found that model scores applied over time showed improvements in symptoms in the patients on active therapies in the clinical trials, compared with patients on placebo.

A specialist in liver pathology and nonalcoholic fatty liver disease who was not involved in the study said in an interview that she finds the results highly promising.
 

Impressive results

Elizabeth M. Brunt, MD, emeritus professor of pathology and immunology at Washington University in St. Louis, was a member of the NASH CRN when SomaLogic first proposed using the groups’ data for this study.

“I was impressed with them then, and I am very impressed with what they’re presenting here, and I can’t say that about all the noninvasive tests,” she said. “I think a lot of noninvasive tests are way over-simplifying what NASH is.”

She acknowledged that, although she spent much of her career performing liver biopsies, “you can’t biopsy every single patients who you suspect of having NASH, or certainly if you want to follow them over time – it’s unrealistic,” she said in an interview.

Although the protein scanning method cannot – and is not intended to – replace a well-conducted biopsy with the interpretation of a skilled pathologist, the proteins the company investigators identified can reflect the dynamic nature of liver disease and the liver’s ability to heal itself with a high degree of accuracy and hold promise for both screening patients and for monitoring responses to therapy, Dr. Brunt said.

The study was sponsored by SomaLogic. The authors are employees of the company. Dr. Brunt had no relevant disclosures.

SOURCE: Ostroff R et al. The Liver Disease Meeting Digital Experience, Abstract LP11

Large-scale scanning of serum proteins offers a potential method for noninvasive screening and monitoring of patients with nonalcoholic steatohepatitis (NASH), the technique’s developers claim.

By scanning for about 5,000 proteins in nearly 3,000 samples from patients enrolled in studies from the Clinical Research Network in NASH (NASH CRN), Rachel Ostroff, PhD, and colleagues from SomaLogic in Boulder, Colo., created four protein models that mimic results of the major pathologic findings in liver tissue biopsy.

“Concurrent positive results from the protein models had performance characteristics of ‘rule-out’ tests for pathologists’ diagnosis of NASH. These tests may assist in new drug development and medical intervention decisions,” they wrote in a late-breaking poster presented at the virtual annual meeting of the American Association for the Study of Liver Diseases.

“There is no single noninvasive method that can accurately and simultaneously capture steatosis, inflammation, hepatocyte ballooning and fibrosis, the four major pathologic components assessed by biopsy. Each of these is relevant to the multiple mechanisms targeted in drug development for NASH,” they wrote.

To see whether large-scale protemoics could serve as an alternative to invasive liver biopsy for use in clinical trials or in longitudinal studies of NASH, they used a modified aptamer proteomics platform to scan for liver-related proteins. Aptamers are olignonucleotide or peptide molecules designed to home in on a specific target.

They scanned for approximately 5,000 proteins in 2,852 serum samples from 638 patients in a NASH CRN natural history cohort, and in patients enrolled in two NASH treatment trials: the PIVENS trial, which is evaluating pioglitazone versus vitamin E and placebo in nondiabetic patients, and the FLINT trial, which is comparing obeticholic acid with placebo. All of the patients in the natural history cohort and half of all patients in the clinical trial cohorts were included in the training sets, with the remaining half included in the validation set.

The accuracy of the models, as measured by the area under the curve (AUC) of receiver operating characteristics in the training and validation sets, respectively, were as follows:

• Fibrosis: AUC 0.92/0.85.
• Steatosis: AUC 0.95/0.79.
• Inflammation: AUC 0.83/0.72.
• Hepatocyte Ballooning: AUC 0.87/0.83.

“A concurrent positive score for steatosis, inflammation and ballooning predicted the biopsy diagnosis of NASH with an accuracy of 73%,” Ostroff and colleagues wrote.

They also found that model scores applied over time showed improvements in symptoms in the patients on active therapies in the clinical trials, compared with patients on placebo.

A specialist in liver pathology and nonalcoholic fatty liver disease who was not involved in the study said in an interview that she finds the results highly promising.
 

Impressive results

Elizabeth M. Brunt, MD, emeritus professor of pathology and immunology at Washington University in St. Louis, was a member of the NASH CRN when SomaLogic first proposed using the groups’ data for this study.

“I was impressed with them then, and I am very impressed with what they’re presenting here, and I can’t say that about all the noninvasive tests,” she said. “I think a lot of noninvasive tests are way over-simplifying what NASH is.”

She acknowledged that, although she spent much of her career performing liver biopsies, “you can’t biopsy every single patients who you suspect of having NASH, or certainly if you want to follow them over time – it’s unrealistic,” she said in an interview.

Although the protein scanning method cannot – and is not intended to – replace a well-conducted biopsy with the interpretation of a skilled pathologist, the proteins the company investigators identified can reflect the dynamic nature of liver disease and the liver’s ability to heal itself with a high degree of accuracy and hold promise for both screening patients and for monitoring responses to therapy, Dr. Brunt said.

The study was sponsored by SomaLogic. The authors are employees of the company. Dr. Brunt had no relevant disclosures.

SOURCE: Ostroff R et al. The Liver Disease Meeting Digital Experience, Abstract LP11

Almost 60% of patients with biopsy-confirmed nonalcoholic steatohepatitis and liver fibrosis showed resolution of NASH after treatment with semaglutide, according to a phase 2, double-blind, randomized, placebo-controlled trial published in the New England Journal of Medicine and presented at the 2020 American Association for the Study of Liver Diseases (AASLD) meeting.

“This bodes well for further study of semaglutide and is supported further by marked improvements in weight, glycemic control and lipid profile,” commented the study’s senior author Philip N. Newsome, PhD, FRCPE, of the University of Birmingham (England), in an interview.

The highest daily dose (0.4 mg) of the glucagonlike peptide-1 (GLP-1) receptor agonist, semaglutide, which is approved for the treatment of type 2 diabetes, led to levels of NASH resolution “which are higher than any previously demonstrated,” noted Dr. Newsome. “This was also accompanied by improvement in noninvasive markers of liver fibrosis and also less fibrosis progression, compared to placebo.”

“I think this represents an exciting advance and will, if confirmed in further studies, mark a step-change in our management of patients with NASH,” he added.

The multicenter study, conducted at 143 sites in 16 countries, included 320 patients, aged 18-75 years, with or without type 2 diabetes, who had histologic evidence of NASH and stage 1-3 liver fibrosis.

They were randomized in a 3:3:3:1:1:1 ratio to receive once-daily subcutaneous semaglutide at a dose of 0.1, 0.2, or 0.4 mg, or placebo for 72 weeks.

The primary endpoint was resolution of NASH and no worsening of fibrosis, with a secondary endpoint being improvement of fibrosis by at least one stage without worsening of NASH.

The study found 40% of patients in the 0.1-mg semaglutide group, 36% in the 0.2-mg group, and 59% in the 0.4-mg group achieved NASH resolution with no worsening of fibrosis, compared with 17% of the placebo group (odds ratio, 6.87; P < .001 for the highest semaglutide dose). However, the treatment did not lead to significant between-group differences in the secondary endpoint, which occurred in 43% of patients on the highest semaglutide dose compared to 33% in the placebo group (OR, 1.42; P = .48).

Treatment with semaglutide also resulted in dose-dependent reductions in body weight, as well as in glycated hemoglobin levels. Bodyweight was reduced by a mean of 5% in the 0.1-mg semaglutide group, followed by mean reductions of 9% and 13% in the 0.2-mg and 0.4-mg groups respectively. This compared to a mean reduction of 1% in the placebo group.

Similarly, glycated hemoglobin levels among patients with type 2 diabetes dropped by 0.63, 1.07, and 1.15 percentage points in the 0.1-mg, 0.2-mg, and 0.4-mg semaglutide groups respectively, compared with a drop of 0.01 percentage point in the placebo group.

“The fact that the percentage of patients who had an improvement in fibrosis stage was not significantly higher with semaglutide than with placebo – despite a greater benefit with respect to NASH resolution and dose-dependent weight loss – was unexpected, given that previous studies have suggested that resolution of NASH and improvements in activity scores for the components of nonalcoholic fatty liver disease are associated with regression of fibrosis,” wrote the authors. “However, the temporal association among NASH resolution, weight loss, and improvement in fibrosis stage is not fully understood. It is possible that the current trial was not of sufficient duration for improvements in fibrosis stage to become apparent.”

The authors also noted that the safety profile of semaglutide was “consistent with that observed in patients with type 2 diabetes in other trials and with the known effects of GLP-1 receptor agonists,” with gastrointestinal disorders being the most commonly reported.

Nausea, constipation, and vomiting were reported more often in the 0.4-mg semaglutide group than in the placebo group (nausea, 42% vs. 11%; constipation, 22% vs. 12%; and vomiting, 15% vs. 2%).

The overall incidence of benign, malignant, or unspecified neoplasms was 15% in the treatment groups versus 8% in the placebo group.

Rowen K. Zetterman, MD, who was not involved with the study, noted that “treatment of NASH is currently limited, and no therapies have yet been approved by the Food and Drug Administration.”

The findings are “important but not yet exciting,” added Dr. Zetterman, who is professor emeritus of internal medicine and associate vice chancellor for strategic planning for the University of Nebraska Medical Center, Omaha.

“Though reversal of liver fibrosis was not noted, the resolution of hepatic inflammation and liver cell injury by semaglutide suggests it may be slowing disease progression,” said Dr. Zetterman, who also serves on the editorial advisory board of Internal Medicine News. This “warrants additional studies where longer treatment with semaglutide may prove reversal of fibrosis and/or prevention of progression to cirrhosis.”

The study was sponsored by Novo Nordisk. Dr. Newsome reported disclosures related to Novo Nordisk during the conduct of the study, and to Boehringer Ingelheim, Bristol-Myers Squibb, Echosens, Gilead, Pfizer, Pharmaxis, and Poxel. Several of the other study authors reported receiving fees and grants from various pharmaceutical companies, including Novo Nordisk One author reported pending patents for the use of semaglutide. Dr. Zetterman had no relevant disclosures.

SOURCE: Newsome PN et al. N Engl J Med. 2020 Nov 13. doi: 10.1056/NEJMoa2028395.

Almost 60% of patients with biopsy-confirmed nonalcoholic steatohepatitis and liver fibrosis showed resolution of NASH after treatment with semaglutide, according to a phase 2, double-blind, randomized, placebo-controlled trial published in the New England Journal of Medicine and presented at the 2020 American Association for the Study of Liver Diseases (AASLD) meeting.

“This bodes well for further study of semaglutide and is supported further by marked improvements in weight, glycemic control and lipid profile,” commented the study’s senior author Philip N. Newsome, PhD, FRCPE, of the University of Birmingham (England), in an interview.

The highest daily dose (0.4 mg) of the glucagonlike peptide-1 (GLP-1) receptor agonist, semaglutide, which is approved for the treatment of type 2 diabetes, led to levels of NASH resolution “which are higher than any previously demonstrated,” noted Dr. Newsome. “This was also accompanied by improvement in noninvasive markers of liver fibrosis and also less fibrosis progression, compared to placebo.”

“I think this represents an exciting advance and will, if confirmed in further studies, mark a step-change in our management of patients with NASH,” he added.

The multicenter study, conducted at 143 sites in 16 countries, included 320 patients, aged 18-75 years, with or without type 2 diabetes, who had histologic evidence of NASH and stage 1-3 liver fibrosis.

They were randomized in a 3:3:3:1:1:1 ratio to receive once-daily subcutaneous semaglutide at a dose of 0.1, 0.2, or 0.4 mg, or placebo for 72 weeks.

The primary endpoint was resolution of NASH and no worsening of fibrosis, with a secondary endpoint being improvement of fibrosis by at least one stage without worsening of NASH.

The study found 40% of patients in the 0.1-mg semaglutide group, 36% in the 0.2-mg group, and 59% in the 0.4-mg group achieved NASH resolution with no worsening of fibrosis, compared with 17% of the placebo group (odds ratio, 6.87; P < .001 for the highest semaglutide dose). However, the treatment did not lead to significant between-group differences in the secondary endpoint, which occurred in 43% of patients on the highest semaglutide dose compared to 33% in the placebo group (OR, 1.42; P = .48).

Treatment with semaglutide also resulted in dose-dependent reductions in body weight, as well as in glycated hemoglobin levels. Bodyweight was reduced by a mean of 5% in the 0.1-mg semaglutide group, followed by mean reductions of 9% and 13% in the 0.2-mg and 0.4-mg groups respectively. This compared to a mean reduction of 1% in the placebo group.

Similarly, glycated hemoglobin levels among patients with type 2 diabetes dropped by 0.63, 1.07, and 1.15 percentage points in the 0.1-mg, 0.2-mg, and 0.4-mg semaglutide groups respectively, compared with a drop of 0.01 percentage point in the placebo group.

“The fact that the percentage of patients who had an improvement in fibrosis stage was not significantly higher with semaglutide than with placebo – despite a greater benefit with respect to NASH resolution and dose-dependent weight loss – was unexpected, given that previous studies have suggested that resolution of NASH and improvements in activity scores for the components of nonalcoholic fatty liver disease are associated with regression of fibrosis,” wrote the authors. “However, the temporal association among NASH resolution, weight loss, and improvement in fibrosis stage is not fully understood. It is possible that the current trial was not of sufficient duration for improvements in fibrosis stage to become apparent.”

The authors also noted that the safety profile of semaglutide was “consistent with that observed in patients with type 2 diabetes in other trials and with the known effects of GLP-1 receptor agonists,” with gastrointestinal disorders being the most commonly reported.

Nausea, constipation, and vomiting were reported more often in the 0.4-mg semaglutide group than in the placebo group (nausea, 42% vs. 11%; constipation, 22% vs. 12%; and vomiting, 15% vs. 2%).

The overall incidence of benign, malignant, or unspecified neoplasms was 15% in the treatment groups versus 8% in the placebo group.

Rowen K. Zetterman, MD, who was not involved with the study, noted that “treatment of NASH is currently limited, and no therapies have yet been approved by the Food and Drug Administration.”

The findings are “important but not yet exciting,” added Dr. Zetterman, who is professor emeritus of internal medicine and associate vice chancellor for strategic planning for the University of Nebraska Medical Center, Omaha.

“Though reversal of liver fibrosis was not noted, the resolution of hepatic inflammation and liver cell injury by semaglutide suggests it may be slowing disease progression,” said Dr. Zetterman, who also serves on the editorial advisory board of Internal Medicine News. This “warrants additional studies where longer treatment with semaglutide may prove reversal of fibrosis and/or prevention of progression to cirrhosis.”

The study was sponsored by Novo Nordisk. Dr. Newsome reported disclosures related to Novo Nordisk during the conduct of the study, and to Boehringer Ingelheim, Bristol-Myers Squibb, Echosens, Gilead, Pfizer, Pharmaxis, and Poxel. Several of the other study authors reported receiving fees and grants from various pharmaceutical companies, including Novo Nordisk One author reported pending patents for the use of semaglutide. Dr. Zetterman had no relevant disclosures.

SOURCE: Newsome PN et al. N Engl J Med. 2020 Nov 13. doi: 10.1056/NEJMoa2028395.

Almost 60% of patients with biopsy-confirmed nonalcoholic steatohepatitis and liver fibrosis showed resolution of NASH after treatment with semaglutide, according to a phase 2, double-blind, randomized, placebo-controlled trial published in the New England Journal of Medicine and presented at the 2020 American Association for the Study of Liver Diseases (AASLD) meeting.

“This bodes well for further study of semaglutide and is supported further by marked improvements in weight, glycemic control and lipid profile,” commented the study’s senior author Philip N. Newsome, PhD, FRCPE, of the University of Birmingham (England), in an interview.

The highest daily dose (0.4 mg) of the glucagonlike peptide-1 (GLP-1) receptor agonist, semaglutide, which is approved for the treatment of type 2 diabetes, led to levels of NASH resolution “which are higher than any previously demonstrated,” noted Dr. Newsome. “This was also accompanied by improvement in noninvasive markers of liver fibrosis and also less fibrosis progression, compared to placebo.”

“I think this represents an exciting advance and will, if confirmed in further studies, mark a step-change in our management of patients with NASH,” he added.

The multicenter study, conducted at 143 sites in 16 countries, included 320 patients, aged 18-75 years, with or without type 2 diabetes, who had histologic evidence of NASH and stage 1-3 liver fibrosis.

They were randomized in a 3:3:3:1:1:1 ratio to receive once-daily subcutaneous semaglutide at a dose of 0.1, 0.2, or 0.4 mg, or placebo for 72 weeks.

The primary endpoint was resolution of NASH and no worsening of fibrosis, with a secondary endpoint being improvement of fibrosis by at least one stage without worsening of NASH.

The study found 40% of patients in the 0.1-mg semaglutide group, 36% in the 0.2-mg group, and 59% in the 0.4-mg group achieved NASH resolution with no worsening of fibrosis, compared with 17% of the placebo group (odds ratio, 6.87; P < .001 for the highest semaglutide dose). However, the treatment did not lead to significant between-group differences in the secondary endpoint, which occurred in 43% of patients on the highest semaglutide dose compared to 33% in the placebo group (OR, 1.42; P = .48).

Treatment with semaglutide also resulted in dose-dependent reductions in body weight, as well as in glycated hemoglobin levels. Bodyweight was reduced by a mean of 5% in the 0.1-mg semaglutide group, followed by mean reductions of 9% and 13% in the 0.2-mg and 0.4-mg groups respectively. This compared to a mean reduction of 1% in the placebo group.

Similarly, glycated hemoglobin levels among patients with type 2 diabetes dropped by 0.63, 1.07, and 1.15 percentage points in the 0.1-mg, 0.2-mg, and 0.4-mg semaglutide groups respectively, compared with a drop of 0.01 percentage point in the placebo group.

“The fact that the percentage of patients who had an improvement in fibrosis stage was not significantly higher with semaglutide than with placebo – despite a greater benefit with respect to NASH resolution and dose-dependent weight loss – was unexpected, given that previous studies have suggested that resolution of NASH and improvements in activity scores for the components of nonalcoholic fatty liver disease are associated with regression of fibrosis,” wrote the authors. “However, the temporal association among NASH resolution, weight loss, and improvement in fibrosis stage is not fully understood. It is possible that the current trial was not of sufficient duration for improvements in fibrosis stage to become apparent.”

The authors also noted that the safety profile of semaglutide was “consistent with that observed in patients with type 2 diabetes in other trials and with the known effects of GLP-1 receptor agonists,” with gastrointestinal disorders being the most commonly reported.

Nausea, constipation, and vomiting were reported more often in the 0.4-mg semaglutide group than in the placebo group (nausea, 42% vs. 11%; constipation, 22% vs. 12%; and vomiting, 15% vs. 2%).

The overall incidence of benign, malignant, or unspecified neoplasms was 15% in the treatment groups versus 8% in the placebo group.

Rowen K. Zetterman, MD, who was not involved with the study, noted that “treatment of NASH is currently limited, and no therapies have yet been approved by the Food and Drug Administration.”

The findings are “important but not yet exciting,” added Dr. Zetterman, who is professor emeritus of internal medicine and associate vice chancellor for strategic planning for the University of Nebraska Medical Center, Omaha.

“Though reversal of liver fibrosis was not noted, the resolution of hepatic inflammation and liver cell injury by semaglutide suggests it may be slowing disease progression,” said Dr. Zetterman, who also serves on the editorial advisory board of Internal Medicine News. This “warrants additional studies where longer treatment with semaglutide may prove reversal of fibrosis and/or prevention of progression to cirrhosis.”

The study was sponsored by Novo Nordisk. Dr. Newsome reported disclosures related to Novo Nordisk during the conduct of the study, and to Boehringer Ingelheim, Bristol-Myers Squibb, Echosens, Gilead, Pfizer, Pharmaxis, and Poxel. Several of the other study authors reported receiving fees and grants from various pharmaceutical companies, including Novo Nordisk One author reported pending patents for the use of semaglutide. Dr. Zetterman had no relevant disclosures.

SOURCE: Newsome PN et al. N Engl J Med. 2020 Nov 13. doi: 10.1056/NEJMoa2028395.

Both obese and nonobese individuals can develop nonalcoholic fatty liver disease (NAFLD), and lipid profiles were effective predictors in both groups, based on data from a cross-sectional study of 361 individuals.

Nephron/Wikimedia/Creative Commons License

Given the strong association between obesity and NAFLD, previous research on lipidomic profiles have focused on obese White patients, wrote Youngae Jung, MD, of the Korea Basic Science Institute, Seoul, and colleagues.

“However, there are insufficient data on circulating lipidomics of nonobese NAFLD patients,” they added.

In a study published in Alimentary Pharmacology and Therapeutics, the researchers identified 295 adults with NAFLD and 66 controls. Overall, 130 participants were nonobese (body mass index <25 kg/m²) and 231 were obese (BMI, 25 or higher). The nonobese group included 51 patients with NAFL, 31 with nonalcoholic steatohepatitis , and 48 controls; the obese group included 106 patients with NAFL, 107 with NASH, and 18 controls.

Lipid profiles show predictive promise

Overall, changes in diacylglycerol (DAG) and triacylglycerol (TAG) appeared in both obese and nonobese patients with increases from NAFL to NASH, the researchers noted.

“Levels of DAGs with relatively short chains and a low degree of desaturation significantly increased in NAFL versus no NAFLD, regardless of obesity,” the researchers said. “In contrast, levels of DAGs with relatively long chains and a high degree of desaturation significantly decreased in NASH versus NAFL in the obese group, which was not observed in the nonobese group,” they noted.

In addition, saturated sphingomyelin (SM) species were significantly associated with visceral adiposity in nonobese NAFLD patients, but not in obese NAFLD patients, and SM levels were significantly associated with both systemic and adipose tissue insulin resistance.

The researchers identified five potential lipid metabolites for nonobese subjects and seven potential lipids for obese subjects that included DAGs, TAGs, and SMs that were distinct between NAFL and NASH patients in order to predict the histologic severity of NAFLD. Overall, these metabolite combinations were effective predictors of NAFLD/NASH in nonobese and obese patients. The areas under the receiver operator characteristic curve were 0.916 versus 0.813 for NAFLD versus non-NAFLD in nonobese patients, and 0.967 versus 0.812 for NAFLD versus non-NAFLD in the obese patients.
 

More BMI groups may yield more information

The key study limitation was the cross-sectional study design, the researchers noted. In addition, dividing patients into only two groups based on BMI may not reveal any distinct biology among lean NAFLD patients, who were included with overweight patients in the nonobese group.

However, the results were strengthened by the large amount of data and the confirmed diagnoses of NASH and fibrosis by an expert liver pathologist, they added.

“Therefore, our findings provide new insights that aid in the understanding of pathophysiological mechanisms responsible for the development and severity of nonobese NAFLD, which are relevant to precision medicine and personalized therapy based on various phenotypes of NAFLD,” they concluded.
 

Validation needed in other populations

“Liver biopsy remains the gold standard for diagnosing NAFLD/NASH but has its own limitations and risks, so many researchers in this field are looking for a noninvasive alternative to help with diagnosis,” Zachary Henry, MD, of the University of Virginia, Charlottesville, said in an interview. “Imaging methods such as transient elastography and MR-elastography have been introduced and many biochemical markers have been evaluated, yet all have their limitations. In the current study, the authors report a high diagnostic accuracy for evaluating NAFLD using lipidomic profiles, which could introduce a new noninvasive measurement of NAFLD.”

Dr. Henry said that he was not surprised by the study findings. However, “I believe they are important as they define a lipid profile that shows differences between patients with NASH versus patients with NAFLD versus patients without NAFLD,” he said. “NAFLD is a disease of disordered lipid metabolism in hepatocytes, and although it stands to reason there would be differences in lipid profiles, it is interesting to see the changes between DAGs and TAGs especially as disease progresses from NAFLD to NASH.

“Clinically, I do not think this really changes practice right now since it needs to be validated in other populations of NAFLD. However, it certainly adds to a growing armamentarium of noninvasive testing. Hopefully, we are able to combine some of these noninvasive tests in the future to better predict NAFLD and NASH as well as outcomes such as cirrhosis and hepatocellular carcinoma,” he said.

“I think these lipidomic profiles need to be validated in non-Korean populations of patients with NAFLD to determine if these changes are ubiquitous to everyone or if a different profile exists based upon different genetics and environment,” Dr. Henry added. “As the authors note in their paper, there have been previously published differences between populations of NAFLD in Asia as compared to Western countries and it is unclear how, if at all, these lipidomic profiles relate to those differences.”

The study was funded by the Korea Basic Science Institute, the Korea Health Industry Department Institute, and the National Research Foundation of Korea. The researchers had no financial conflicts to disclose. Dr. Henry had no financial conflicts to disclose.

SOURCE: Jung Y et al. Aliment Pharmacol Ther. 2020 Sep 6. doi: 10.1111/apt.16066.

Both obese and nonobese individuals can develop nonalcoholic fatty liver disease (NAFLD), and lipid profiles were effective predictors in both groups, based on data from a cross-sectional study of 361 individuals.

Nephron/Wikimedia/Creative Commons License

Given the strong association between obesity and NAFLD, previous research on lipidomic profiles have focused on obese White patients, wrote Youngae Jung, MD, of the Korea Basic Science Institute, Seoul, and colleagues.

“However, there are insufficient data on circulating lipidomics of nonobese NAFLD patients,” they added.

In a study published in Alimentary Pharmacology and Therapeutics, the researchers identified 295 adults with NAFLD and 66 controls. Overall, 130 participants were nonobese (body mass index <25 kg/m²) and 231 were obese (BMI, 25 or higher). The nonobese group included 51 patients with NAFL, 31 with nonalcoholic steatohepatitis , and 48 controls; the obese group included 106 patients with NAFL, 107 with NASH, and 18 controls.

Lipid profiles show predictive promise

Overall, changes in diacylglycerol (DAG) and triacylglycerol (TAG) appeared in both obese and nonobese patients with increases from NAFL to NASH, the researchers noted.

“Levels of DAGs with relatively short chains and a low degree of desaturation significantly increased in NAFL versus no NAFLD, regardless of obesity,” the researchers said. “In contrast, levels of DAGs with relatively long chains and a high degree of desaturation significantly decreased in NASH versus NAFL in the obese group, which was not observed in the nonobese group,” they noted.

In addition, saturated sphingomyelin (SM) species were significantly associated with visceral adiposity in nonobese NAFLD patients, but not in obese NAFLD patients, and SM levels were significantly associated with both systemic and adipose tissue insulin resistance.

The researchers identified five potential lipid metabolites for nonobese subjects and seven potential lipids for obese subjects that included DAGs, TAGs, and SMs that were distinct between NAFL and NASH patients in order to predict the histologic severity of NAFLD. Overall, these metabolite combinations were effective predictors of NAFLD/NASH in nonobese and obese patients. The areas under the receiver operator characteristic curve were 0.916 versus 0.813 for NAFLD versus non-NAFLD in nonobese patients, and 0.967 versus 0.812 for NAFLD versus non-NAFLD in the obese patients.
 

More BMI groups may yield more information

The key study limitation was the cross-sectional study design, the researchers noted. In addition, dividing patients into only two groups based on BMI may not reveal any distinct biology among lean NAFLD patients, who were included with overweight patients in the nonobese group.

However, the results were strengthened by the large amount of data and the confirmed diagnoses of NASH and fibrosis by an expert liver pathologist, they added.

“Therefore, our findings provide new insights that aid in the understanding of pathophysiological mechanisms responsible for the development and severity of nonobese NAFLD, which are relevant to precision medicine and personalized therapy based on various phenotypes of NAFLD,” they concluded.
 

Validation needed in other populations

“Liver biopsy remains the gold standard for diagnosing NAFLD/NASH but has its own limitations and risks, so many researchers in this field are looking for a noninvasive alternative to help with diagnosis,” Zachary Henry, MD, of the University of Virginia, Charlottesville, said in an interview. “Imaging methods such as transient elastography and MR-elastography have been introduced and many biochemical markers have been evaluated, yet all have their limitations. In the current study, the authors report a high diagnostic accuracy for evaluating NAFLD using lipidomic profiles, which could introduce a new noninvasive measurement of NAFLD.”

Dr. Henry said that he was not surprised by the study findings. However, “I believe they are important as they define a lipid profile that shows differences between patients with NASH versus patients with NAFLD versus patients without NAFLD,” he said. “NAFLD is a disease of disordered lipid metabolism in hepatocytes, and although it stands to reason there would be differences in lipid profiles, it is interesting to see the changes between DAGs and TAGs especially as disease progresses from NAFLD to NASH.

“Clinically, I do not think this really changes practice right now since it needs to be validated in other populations of NAFLD. However, it certainly adds to a growing armamentarium of noninvasive testing. Hopefully, we are able to combine some of these noninvasive tests in the future to better predict NAFLD and NASH as well as outcomes such as cirrhosis and hepatocellular carcinoma,” he said.

“I think these lipidomic profiles need to be validated in non-Korean populations of patients with NAFLD to determine if these changes are ubiquitous to everyone or if a different profile exists based upon different genetics and environment,” Dr. Henry added. “As the authors note in their paper, there have been previously published differences between populations of NAFLD in Asia as compared to Western countries and it is unclear how, if at all, these lipidomic profiles relate to those differences.”

The study was funded by the Korea Basic Science Institute, the Korea Health Industry Department Institute, and the National Research Foundation of Korea. The researchers had no financial conflicts to disclose. Dr. Henry had no financial conflicts to disclose.

SOURCE: Jung Y et al. Aliment Pharmacol Ther. 2020 Sep 6. doi: 10.1111/apt.16066.

Both obese and nonobese individuals can develop nonalcoholic fatty liver disease (NAFLD), and lipid profiles were effective predictors in both groups, based on data from a cross-sectional study of 361 individuals.

Nephron/Wikimedia/Creative Commons License

Given the strong association between obesity and NAFLD, previous research on lipidomic profiles have focused on obese White patients, wrote Youngae Jung, MD, of the Korea Basic Science Institute, Seoul, and colleagues.

“However, there are insufficient data on circulating lipidomics of nonobese NAFLD patients,” they added.

In a study published in Alimentary Pharmacology and Therapeutics, the researchers identified 295 adults with NAFLD and 66 controls. Overall, 130 participants were nonobese (body mass index <25 kg/m²) and 231 were obese (BMI, 25 or higher). The nonobese group included 51 patients with NAFL, 31 with nonalcoholic steatohepatitis , and 48 controls; the obese group included 106 patients with NAFL, 107 with NASH, and 18 controls.

Lipid profiles show predictive promise

Overall, changes in diacylglycerol (DAG) and triacylglycerol (TAG) appeared in both obese and nonobese patients with increases from NAFL to NASH, the researchers noted.

“Levels of DAGs with relatively short chains and a low degree of desaturation significantly increased in NAFL versus no NAFLD, regardless of obesity,” the researchers said. “In contrast, levels of DAGs with relatively long chains and a high degree of desaturation significantly decreased in NASH versus NAFL in the obese group, which was not observed in the nonobese group,” they noted.

In addition, saturated sphingomyelin (SM) species were significantly associated with visceral adiposity in nonobese NAFLD patients, but not in obese NAFLD patients, and SM levels were significantly associated with both systemic and adipose tissue insulin resistance.

The researchers identified five potential lipid metabolites for nonobese subjects and seven potential lipids for obese subjects that included DAGs, TAGs, and SMs that were distinct between NAFL and NASH patients in order to predict the histologic severity of NAFLD. Overall, these metabolite combinations were effective predictors of NAFLD/NASH in nonobese and obese patients. The areas under the receiver operator characteristic curve were 0.916 versus 0.813 for NAFLD versus non-NAFLD in nonobese patients, and 0.967 versus 0.812 for NAFLD versus non-NAFLD in the obese patients.
 

More BMI groups may yield more information

The key study limitation was the cross-sectional study design, the researchers noted. In addition, dividing patients into only two groups based on BMI may not reveal any distinct biology among lean NAFLD patients, who were included with overweight patients in the nonobese group.

However, the results were strengthened by the large amount of data and the confirmed diagnoses of NASH and fibrosis by an expert liver pathologist, they added.

“Therefore, our findings provide new insights that aid in the understanding of pathophysiological mechanisms responsible for the development and severity of nonobese NAFLD, which are relevant to precision medicine and personalized therapy based on various phenotypes of NAFLD,” they concluded.
 

Validation needed in other populations

“Liver biopsy remains the gold standard for diagnosing NAFLD/NASH but has its own limitations and risks, so many researchers in this field are looking for a noninvasive alternative to help with diagnosis,” Zachary Henry, MD, of the University of Virginia, Charlottesville, said in an interview. “Imaging methods such as transient elastography and MR-elastography have been introduced and many biochemical markers have been evaluated, yet all have their limitations. In the current study, the authors report a high diagnostic accuracy for evaluating NAFLD using lipidomic profiles, which could introduce a new noninvasive measurement of NAFLD.”

Dr. Henry said that he was not surprised by the study findings. However, “I believe they are important as they define a lipid profile that shows differences between patients with NASH versus patients with NAFLD versus patients without NAFLD,” he said. “NAFLD is a disease of disordered lipid metabolism in hepatocytes, and although it stands to reason there would be differences in lipid profiles, it is interesting to see the changes between DAGs and TAGs especially as disease progresses from NAFLD to NASH.

“Clinically, I do not think this really changes practice right now since it needs to be validated in other populations of NAFLD. However, it certainly adds to a growing armamentarium of noninvasive testing. Hopefully, we are able to combine some of these noninvasive tests in the future to better predict NAFLD and NASH as well as outcomes such as cirrhosis and hepatocellular carcinoma,” he said.

“I think these lipidomic profiles need to be validated in non-Korean populations of patients with NAFLD to determine if these changes are ubiquitous to everyone or if a different profile exists based upon different genetics and environment,” Dr. Henry added. “As the authors note in their paper, there have been previously published differences between populations of NAFLD in Asia as compared to Western countries and it is unclear how, if at all, these lipidomic profiles relate to those differences.”

The study was funded by the Korea Basic Science Institute, the Korea Health Industry Department Institute, and the National Research Foundation of Korea. The researchers had no financial conflicts to disclose. Dr. Henry had no financial conflicts to disclose.

SOURCE: Jung Y et al. Aliment Pharmacol Ther. 2020 Sep 6. doi: 10.1111/apt.16066.

Cirrhosis may increase the risk of complications from endoscopic retrograde cholangiopancreatography (ERCP), according to a retrospective study involving almost 700 patients.

The study also showed that Child-Pugh class was a better predictor of risk than Model for End-Stage Liver Disease (MELD) score, reported lead author Michelle Bernshteyn, MD, a third-year internal medicine resident at State University of New York, Syracuse , and colleagues.

“There remains a scarcity in the literature regarding complications and adverse effects after ERCP in cirrhotic patients, particularly those incorporating Child-Pugh class and MELD score or type of intervention as predictors,” Dr. Bernshteyn said during a virtual presentation at the American College of Gastroenterology annual meeting. “Furthermore, literature review demonstrates inconsistency among results.”

To gain clarity, Dr. Bernshteyn and colleagues reviewed electronic medical records from 692 patients who underwent ERCP, of whom 174 had cirrhosis and 518 did not. For all patients, the investigators analyzed demographics, comorbidities, indications for ERCP, type of sedation, type of intervention, and complications within a 30-day period. Complications included bleeding, pancreatitis, cholangitis, perforation, mortality caused by ERCP, and mortality from other causes. Patients with cirrhosis were further analyzed based on etiology of cirrhosis, Child-Pugh class, and MELD score.

The analysis revealed that complications were significantly more common in patients with cirrhosis than in those without cirrhosis (21.30% vs. 13.51%; P = .015). No specific complications were significantly more common in patients with cirrhosis than in those without cirrhosis.

In patients with cirrhosis, 41.18% of Child-Pugh class C patients had complications, compared with 15.15% of class B patients and 19.30% of class A patients (P = .010). In contrast, MELD scores were not significantly associated with adverse events.

Further analysis showed that, in patients without cirrhosis, diagnostic-only ERCP and underlying chronic obstructive pulmonary disease were associated with high rates of complications (P = .039 and P = .003, respectively). In patients with cirrhosis, underlying chronic obstructive pulmonary disease and hypertension predicted adverse events (P = .009 and P = .003, respectively).

“The results of our study reaffirm that liver cirrhosis has an impact on the occurrence of complications during ERCP,” Dr. Bernshteyn said. “Child-Pugh class seems to be more reliable as compared to MELD score in predicting complications of ERCP in cirrhosis patients,” she added. “However, we are also aware that Child-Pugh and MELD scores are complementary to each other while evaluating outcomes of any surgery in patients with cirrhosis.”

In 2017, Udayakumar Navaneethan, MD, a gastroenterologist at AdventHealth Orlando’s Center for Interventional Endoscopy, and an assistant professor at the University of Central Florida, Orlando, and colleagues published a national database study concerning the safety of ERCP in patients with liver cirrhosis.

“[The present] study is important as it highlights the fact that ERCP is associated with significant complications in cirrhotic patients compared to those without cirrhosis,” Dr. Navaneethan said when asked to comment. “Also, Child-Pugh score appeared to be more reliable than MELD score in predicting complications of ERCP in cirrhotic patients.”

He went on to explain relevance for practicing clinicians. “The clinical implications of the study are that a detailed risk-benefit discussion needs to be done with patients with liver cirrhosis, particularly with advanced liver disease Child-Pugh class C, irrespective of the etiology,” Dr. Navaneethan said. “ERCP should be performed when there is clear evidence that the benefits outweigh the risks.” The investigators and Dr. Navaneethan reported no conflicts of interest.

SOURCE: Bernshteyn M et al. ACG 2020, Abstract S0982.

Cirrhosis may increase the risk of complications from endoscopic retrograde cholangiopancreatography (ERCP), according to a retrospective study involving almost 700 patients.

The study also showed that Child-Pugh class was a better predictor of risk than Model for End-Stage Liver Disease (MELD) score, reported lead author Michelle Bernshteyn, MD, a third-year internal medicine resident at State University of New York, Syracuse , and colleagues.

“There remains a scarcity in the literature regarding complications and adverse effects after ERCP in cirrhotic patients, particularly those incorporating Child-Pugh class and MELD score or type of intervention as predictors,” Dr. Bernshteyn said during a virtual presentation at the American College of Gastroenterology annual meeting. “Furthermore, literature review demonstrates inconsistency among results.”

To gain clarity, Dr. Bernshteyn and colleagues reviewed electronic medical records from 692 patients who underwent ERCP, of whom 174 had cirrhosis and 518 did not. For all patients, the investigators analyzed demographics, comorbidities, indications for ERCP, type of sedation, type of intervention, and complications within a 30-day period. Complications included bleeding, pancreatitis, cholangitis, perforation, mortality caused by ERCP, and mortality from other causes. Patients with cirrhosis were further analyzed based on etiology of cirrhosis, Child-Pugh class, and MELD score.

The analysis revealed that complications were significantly more common in patients with cirrhosis than in those without cirrhosis (21.30% vs. 13.51%; P = .015). No specific complications were significantly more common in patients with cirrhosis than in those without cirrhosis.

In patients with cirrhosis, 41.18% of Child-Pugh class C patients had complications, compared with 15.15% of class B patients and 19.30% of class A patients (P = .010). In contrast, MELD scores were not significantly associated with adverse events.

Further analysis showed that, in patients without cirrhosis, diagnostic-only ERCP and underlying chronic obstructive pulmonary disease were associated with high rates of complications (P = .039 and P = .003, respectively). In patients with cirrhosis, underlying chronic obstructive pulmonary disease and hypertension predicted adverse events (P = .009 and P = .003, respectively).

“The results of our study reaffirm that liver cirrhosis has an impact on the occurrence of complications during ERCP,” Dr. Bernshteyn said. “Child-Pugh class seems to be more reliable as compared to MELD score in predicting complications of ERCP in cirrhosis patients,” she added. “However, we are also aware that Child-Pugh and MELD scores are complementary to each other while evaluating outcomes of any surgery in patients with cirrhosis.”

In 2017, Udayakumar Navaneethan, MD, a gastroenterologist at AdventHealth Orlando’s Center for Interventional Endoscopy, and an assistant professor at the University of Central Florida, Orlando, and colleagues published a national database study concerning the safety of ERCP in patients with liver cirrhosis.

“[The present] study is important as it highlights the fact that ERCP is associated with significant complications in cirrhotic patients compared to those without cirrhosis,” Dr. Navaneethan said when asked to comment. “Also, Child-Pugh score appeared to be more reliable than MELD score in predicting complications of ERCP in cirrhotic patients.”

He went on to explain relevance for practicing clinicians. “The clinical implications of the study are that a detailed risk-benefit discussion needs to be done with patients with liver cirrhosis, particularly with advanced liver disease Child-Pugh class C, irrespective of the etiology,” Dr. Navaneethan said. “ERCP should be performed when there is clear evidence that the benefits outweigh the risks.” The investigators and Dr. Navaneethan reported no conflicts of interest.

SOURCE: Bernshteyn M et al. ACG 2020, Abstract S0982.

Cirrhosis may increase the risk of complications from endoscopic retrograde cholangiopancreatography (ERCP), according to a retrospective study involving almost 700 patients.

The study also showed that Child-Pugh class was a better predictor of risk than Model for End-Stage Liver Disease (MELD) score, reported lead author Michelle Bernshteyn, MD, a third-year internal medicine resident at State University of New York, Syracuse , and colleagues.

“There remains a scarcity in the literature regarding complications and adverse effects after ERCP in cirrhotic patients, particularly those incorporating Child-Pugh class and MELD score or type of intervention as predictors,” Dr. Bernshteyn said during a virtual presentation at the American College of Gastroenterology annual meeting. “Furthermore, literature review demonstrates inconsistency among results.”

To gain clarity, Dr. Bernshteyn and colleagues reviewed electronic medical records from 692 patients who underwent ERCP, of whom 174 had cirrhosis and 518 did not. For all patients, the investigators analyzed demographics, comorbidities, indications for ERCP, type of sedation, type of intervention, and complications within a 30-day period. Complications included bleeding, pancreatitis, cholangitis, perforation, mortality caused by ERCP, and mortality from other causes. Patients with cirrhosis were further analyzed based on etiology of cirrhosis, Child-Pugh class, and MELD score.

The analysis revealed that complications were significantly more common in patients with cirrhosis than in those without cirrhosis (21.30% vs. 13.51%; P = .015). No specific complications were significantly more common in patients with cirrhosis than in those without cirrhosis.

In patients with cirrhosis, 41.18% of Child-Pugh class C patients had complications, compared with 15.15% of class B patients and 19.30% of class A patients (P = .010). In contrast, MELD scores were not significantly associated with adverse events.

Further analysis showed that, in patients without cirrhosis, diagnostic-only ERCP and underlying chronic obstructive pulmonary disease were associated with high rates of complications (P = .039 and P = .003, respectively). In patients with cirrhosis, underlying chronic obstructive pulmonary disease and hypertension predicted adverse events (P = .009 and P = .003, respectively).

“The results of our study reaffirm that liver cirrhosis has an impact on the occurrence of complications during ERCP,” Dr. Bernshteyn said. “Child-Pugh class seems to be more reliable as compared to MELD score in predicting complications of ERCP in cirrhosis patients,” she added. “However, we are also aware that Child-Pugh and MELD scores are complementary to each other while evaluating outcomes of any surgery in patients with cirrhosis.”

In 2017, Udayakumar Navaneethan, MD, a gastroenterologist at AdventHealth Orlando’s Center for Interventional Endoscopy, and an assistant professor at the University of Central Florida, Orlando, and colleagues published a national database study concerning the safety of ERCP in patients with liver cirrhosis.

“[The present] study is important as it highlights the fact that ERCP is associated with significant complications in cirrhotic patients compared to those without cirrhosis,” Dr. Navaneethan said when asked to comment. “Also, Child-Pugh score appeared to be more reliable than MELD score in predicting complications of ERCP in cirrhotic patients.”

He went on to explain relevance for practicing clinicians. “The clinical implications of the study are that a detailed risk-benefit discussion needs to be done with patients with liver cirrhosis, particularly with advanced liver disease Child-Pugh class C, irrespective of the etiology,” Dr. Navaneethan said. “ERCP should be performed when there is clear evidence that the benefits outweigh the risks.” The investigators and Dr. Navaneethan reported no conflicts of interest.

SOURCE: Bernshteyn M et al. ACG 2020, Abstract S0982.

Preemptive monitoring and treatment of cytomegalovirus infections in CMV-seronegative liver transplant recipients who receive organs from CMV-positive donors appears to be better at preventing infections than a viral prophylaxis strategy, according to infectious disease and organ transplant specialists.

In a study published in JAMA that may have gotten scant notice because of its publication during the early days of the COVID-19 pandemic, investigators at the University of Pittsburgh and other transplant centers reported results of a randomized clinical trial comparing the two CMV management strategies, and found that the incidence of CMV disease was significantly lower for patients who were started on valganciclovir when asymptomatic CMV viremia was detected, compared with patients on antiviral prophylaxis with valganciclovir.

The study “is a significant game changer for the field of transplantation,” commented Michael G. Ison, MD, professor of infectious diseases and organ transplantation at Northwestern University, Chicago.

Dr. Ison discussed the study and its implications during a session on potentially practice-changing clinical trials presented virtually during IDWeek 2020, an annual scientific meeting on infectious diseases.

In the trial, Nina Singh, MD, and colleagues randomly assigned 100 CMV-seronegative liver transplant recipients to receive preemptive therapy, in which patients underwent weekly testing for 100 days with a highly sensitive real-time plasma polymerase chain reaction assay for CMV. If viremia at any level was detected, the patients received oral valganciclovir 900 mg twice daily until two consecutive tests performed 1 week apart came back negative.

The remaining 105 patients were randomly assigned to 100 days of oral prophylaxis with 900 mg valganciclovir twice daily, started within 10 days of transplant.
 

CMV disease incidence lower

The incidence of CMV disease within 12 months of transplants, the primary outcome, was 9% in the preemptive therapy group, compared with 19% in the prophylaxis group (P = .04)

The difference between the groups was largely accounted for by a reduction in disease onset beyond 100 days in the preemptive therapy group (6% vs. 17%, respectively, P = .01)

There were no significant differences in secondary endpoints of rejection, opportunistic infections, graft loss because of retransplantation, neutropenia, or receipt of one or more doses of granulocyte colony–stimulating factor for the management of neutropenia.

At 1-year follow-up, the incidence of all-cause mortality was 15% in the preemptive therapy group, and 19% in the prophylaxis group; the difference was not statistically significant.

“While most transplant centers utilize universal prophylaxis, I think that this study really suggests that preemptive monitoring, if it can be safely accomplished at your center, may be of the greatest benefit to your patients,” Dr. Ison said.

He noted that Singh et al. also looked in an exploratory analysis at CMV-specific immunity and observed that patients assigned to preemptive therapy “clearly had better CMV-specific immunity, whether CD4 or CD8 cells, and had higher lymphocyte numbers than those patients that had received universal prophylaxis.”

In a comment, Sarah Doernberg, MD, from the division of infectious diseases at the University of California, San Francisco, agreed that “exploratory analysis of CMV-specific immune responses suggested increased CMV-specific immunity in those in the preemptive group, a finding that warrants further study. The feasibility of adopting reliable preemptive monitoring must be considered as individual centers ponder adopting this approach.”

Dr. Doernberg moderated the session where Dr. Ison discussed the data, but was not involved in the research.

The study by Singh et al. was supported by the National Institutes of Health. Dr. Singh reported research grants from NIH. Dr. Ison disclosed research support and paid consultation for several companies. Dr. Doernberg disclosed consulting for Basilea and Genentech.

Preemptive monitoring and treatment of cytomegalovirus infections in CMV-seronegative liver transplant recipients who receive organs from CMV-positive donors appears to be better at preventing infections than a viral prophylaxis strategy, according to infectious disease and organ transplant specialists.

In a study published in JAMA that may have gotten scant notice because of its publication during the early days of the COVID-19 pandemic, investigators at the University of Pittsburgh and other transplant centers reported results of a randomized clinical trial comparing the two CMV management strategies, and found that the incidence of CMV disease was significantly lower for patients who were started on valganciclovir when asymptomatic CMV viremia was detected, compared with patients on antiviral prophylaxis with valganciclovir.

The study “is a significant game changer for the field of transplantation,” commented Michael G. Ison, MD, professor of infectious diseases and organ transplantation at Northwestern University, Chicago.

Dr. Ison discussed the study and its implications during a session on potentially practice-changing clinical trials presented virtually during IDWeek 2020, an annual scientific meeting on infectious diseases.

In the trial, Nina Singh, MD, and colleagues randomly assigned 100 CMV-seronegative liver transplant recipients to receive preemptive therapy, in which patients underwent weekly testing for 100 days with a highly sensitive real-time plasma polymerase chain reaction assay for CMV. If viremia at any level was detected, the patients received oral valganciclovir 900 mg twice daily until two consecutive tests performed 1 week apart came back negative.

The remaining 105 patients were randomly assigned to 100 days of oral prophylaxis with 900 mg valganciclovir twice daily, started within 10 days of transplant.
 

CMV disease incidence lower

The incidence of CMV disease within 12 months of transplants, the primary outcome, was 9% in the preemptive therapy group, compared with 19% in the prophylaxis group (P = .04)

The difference between the groups was largely accounted for by a reduction in disease onset beyond 100 days in the preemptive therapy group (6% vs. 17%, respectively, P = .01)

There were no significant differences in secondary endpoints of rejection, opportunistic infections, graft loss because of retransplantation, neutropenia, or receipt of one or more doses of granulocyte colony–stimulating factor for the management of neutropenia.

At 1-year follow-up, the incidence of all-cause mortality was 15% in the preemptive therapy group, and 19% in the prophylaxis group; the difference was not statistically significant.

“While most transplant centers utilize universal prophylaxis, I think that this study really suggests that preemptive monitoring, if it can be safely accomplished at your center, may be of the greatest benefit to your patients,” Dr. Ison said.

He noted that Singh et al. also looked in an exploratory analysis at CMV-specific immunity and observed that patients assigned to preemptive therapy “clearly had better CMV-specific immunity, whether CD4 or CD8 cells, and had higher lymphocyte numbers than those patients that had received universal prophylaxis.”

In a comment, Sarah Doernberg, MD, from the division of infectious diseases at the University of California, San Francisco, agreed that “exploratory analysis of CMV-specific immune responses suggested increased CMV-specific immunity in those in the preemptive group, a finding that warrants further study. The feasibility of adopting reliable preemptive monitoring must be considered as individual centers ponder adopting this approach.”

Dr. Doernberg moderated the session where Dr. Ison discussed the data, but was not involved in the research.

The study by Singh et al. was supported by the National Institutes of Health. Dr. Singh reported research grants from NIH. Dr. Ison disclosed research support and paid consultation for several companies. Dr. Doernberg disclosed consulting for Basilea and Genentech.

Preemptive monitoring and treatment of cytomegalovirus infections in CMV-seronegative liver transplant recipients who receive organs from CMV-positive donors appears to be better at preventing infections than a viral prophylaxis strategy, according to infectious disease and organ transplant specialists.

In a study published in JAMA that may have gotten scant notice because of its publication during the early days of the COVID-19 pandemic, investigators at the University of Pittsburgh and other transplant centers reported results of a randomized clinical trial comparing the two CMV management strategies, and found that the incidence of CMV disease was significantly lower for patients who were started on valganciclovir when asymptomatic CMV viremia was detected, compared with patients on antiviral prophylaxis with valganciclovir.

The study “is a significant game changer for the field of transplantation,” commented Michael G. Ison, MD, professor of infectious diseases and organ transplantation at Northwestern University, Chicago.

Dr. Ison discussed the study and its implications during a session on potentially practice-changing clinical trials presented virtually during IDWeek 2020, an annual scientific meeting on infectious diseases.

In the trial, Nina Singh, MD, and colleagues randomly assigned 100 CMV-seronegative liver transplant recipients to receive preemptive therapy, in which patients underwent weekly testing for 100 days with a highly sensitive real-time plasma polymerase chain reaction assay for CMV. If viremia at any level was detected, the patients received oral valganciclovir 900 mg twice daily until two consecutive tests performed 1 week apart came back negative.

The remaining 105 patients were randomly assigned to 100 days of oral prophylaxis with 900 mg valganciclovir twice daily, started within 10 days of transplant.
 

CMV disease incidence lower

The incidence of CMV disease within 12 months of transplants, the primary outcome, was 9% in the preemptive therapy group, compared with 19% in the prophylaxis group (P = .04)

The difference between the groups was largely accounted for by a reduction in disease onset beyond 100 days in the preemptive therapy group (6% vs. 17%, respectively, P = .01)

There were no significant differences in secondary endpoints of rejection, opportunistic infections, graft loss because of retransplantation, neutropenia, or receipt of one or more doses of granulocyte colony–stimulating factor for the management of neutropenia.

At 1-year follow-up, the incidence of all-cause mortality was 15% in the preemptive therapy group, and 19% in the prophylaxis group; the difference was not statistically significant.

“While most transplant centers utilize universal prophylaxis, I think that this study really suggests that preemptive monitoring, if it can be safely accomplished at your center, may be of the greatest benefit to your patients,” Dr. Ison said.

He noted that Singh et al. also looked in an exploratory analysis at CMV-specific immunity and observed that patients assigned to preemptive therapy “clearly had better CMV-specific immunity, whether CD4 or CD8 cells, and had higher lymphocyte numbers than those patients that had received universal prophylaxis.”

In a comment, Sarah Doernberg, MD, from the division of infectious diseases at the University of California, San Francisco, agreed that “exploratory analysis of CMV-specific immune responses suggested increased CMV-specific immunity in those in the preemptive group, a finding that warrants further study. The feasibility of adopting reliable preemptive monitoring must be considered as individual centers ponder adopting this approach.”

Dr. Doernberg moderated the session where Dr. Ison discussed the data, but was not involved in the research.

The study by Singh et al. was supported by the National Institutes of Health. Dr. Singh reported research grants from NIH. Dr. Ison disclosed research support and paid consultation for several companies. Dr. Doernberg disclosed consulting for Basilea and Genentech.

International normalized ratio (INR) does not predict periprocedural bleeding in patients with cirrhosis, according to a meta-analysis of 29 studies.

This finding should deter the common practice of delivering blood products to cirrhotic patients with an elevated INR, reported lead author Alexander J. Kovalic, MD, of Novant Forsyth Medical Center in Winston Salem, N.C., and colleagues.

“INR measurement among cirrhotic patients is important in MELD [Model for End-Stage Liver Disease] prognostication and assessment of underlying hepatic synthetic function, however the INR alone does not capture the complicated interplay of anticoagulant and procoagulant deficiencies present in cirrhotic coagulopathy,” Dr. Kovalic and colleagues wrote in Alimentary Pharmacology & Therapeutics. “Yet, the ‘correction’ of these aberrancies among peripheral coagulation tests remains common ... even in modern practice, and not uncommonly occurs in the periprocedural setting.”

According to investigators, addressing INR with blood transfusion can have a litany of negative effects. Beyond the risks faced by all patient populations, increasing blood volume in those with cirrhosis can increase portal venous pressure, thereby raising risks of portal gastropathy or variceal hemorrhage. In addition, giving plasma products to patients with cirrhotic coagulopathy may further disrupt the balance between anticoagulants and procoagulants, potentially triggering disseminated intravascular coagulation.

Dr. Kovalic and colleagues noted that the lack of correlation between peripheral coagulation tests and bleeding risk has been a longstanding subject of investigation, citing studies from as early as 1981.

To add further weight to this body of evidence, the investigators conducted a systematic review and meta-analysis involving 13,276 patients with cirrhosis who underwent various procedures between 1999 and 2019. Primary outcomes included periprocedural bleeding events and the association between preprocedural INR and periprocedural bleeding events. Secondary outcomes included mortality, quantity of blood and/or plasma products used, and relationship between preprocedural platelet count and periprocedural bleeding events.

The analysis showed that preprocedural INR was not significantly associated with periprocedural bleeding events (pooled odds ratio, 1.52; 95% confidence interval, 0.99-2.33; P = .06), a finding that held across INR threshold subgroups. Similarly, no significant difference was found between mean INR of patients who had bleeding events versus that of those who did not (pooled mean difference, 0.05; 95% CI, 0.03-0.13; P = .23).

Preprocedural platelet count was also a poor predictor of periprocedural bleeding, with a pooled odds ratio of 1.24 (95% CI, 0.55-2.77; P = .60), although the investigators noted that platelet count thresholds varied widely across studies, from 30 to 150 × 10⁹/L. When studies were stratified by procedural bleeding risk or procedure type, subgroup effects were no longer significant. Other secondary endpoints were incalculable because of insufficient data.

“Hopefully, these findings will spark initiation of more large-scale, higher-quality studies ... to reinforce minimizing administration of fresh frozen plasma for inappropriate correction of INR, which carries a multitude of adverse effects among cirrhotic [patients],” the investigators concluded.

According to Stephen H. Caldwell, MD, of the University of Virginia in Charlottesville, “The present paper augments accumulating literature over the past 15 years that INR should be discarded as a measure of procedure-related bleeding risk.”

Dr. Caldwell pointed out that “bleeding in cirrhosis is usually related to portal hypertension not with impaired hemostasis, with the occasional exception of hyperfibrinolysis, which is very different from a prolonged INR.”

He went on to suggest that the present findings should dissuade clinicians from a practice that, for some, is reflexive rather than evidence based.

“It’s remarkable how many medical practices become entrenched based on hand-me-down teaching during our early training years, and remain so for many years beyond as we disperse into various medical and surgical fields,” Dr. Caldwell said. “These learned approaches to common problems can clearly persist for generations despite overwhelming evidence to the contrary that usually evolve slowly and well-insulated within subspecialties or sub-subspecialties, and hence take several generations of training to diffuse into the wider practice of medical care for common problems. These may become matters of expedience in decision-making, much like the old antibiotic conundrum of ‘no-think-a-cillin,’ as critics referred to over-use of broad spectrum antibiotics. And so it has been with the INR.”The investigators disclosed relationships with AbbVie, Eisai, Gilead, and others. Dr. Caldwell disclosed research support from Daiichi concerning the potential role of anticoagulation therapy in preventing cirrhosis progression.

SOURCE: Kovalic AJ et al. Aliment Pharmacol Ther. 2020 Sep 10. doi: 10.1111/apt.16078.

International normalized ratio (INR) does not predict periprocedural bleeding in patients with cirrhosis, according to a meta-analysis of 29 studies.

This finding should deter the common practice of delivering blood products to cirrhotic patients with an elevated INR, reported lead author Alexander J. Kovalic, MD, of Novant Forsyth Medical Center in Winston Salem, N.C., and colleagues.

“INR measurement among cirrhotic patients is important in MELD [Model for End-Stage Liver Disease] prognostication and assessment of underlying hepatic synthetic function, however the INR alone does not capture the complicated interplay of anticoagulant and procoagulant deficiencies present in cirrhotic coagulopathy,” Dr. Kovalic and colleagues wrote in Alimentary Pharmacology & Therapeutics. “Yet, the ‘correction’ of these aberrancies among peripheral coagulation tests remains common ... even in modern practice, and not uncommonly occurs in the periprocedural setting.”

According to investigators, addressing INR with blood transfusion can have a litany of negative effects. Beyond the risks faced by all patient populations, increasing blood volume in those with cirrhosis can increase portal venous pressure, thereby raising risks of portal gastropathy or variceal hemorrhage. In addition, giving plasma products to patients with cirrhotic coagulopathy may further disrupt the balance between anticoagulants and procoagulants, potentially triggering disseminated intravascular coagulation.

Dr. Kovalic and colleagues noted that the lack of correlation between peripheral coagulation tests and bleeding risk has been a longstanding subject of investigation, citing studies from as early as 1981.

To add further weight to this body of evidence, the investigators conducted a systematic review and meta-analysis involving 13,276 patients with cirrhosis who underwent various procedures between 1999 and 2019. Primary outcomes included periprocedural bleeding events and the association between preprocedural INR and periprocedural bleeding events. Secondary outcomes included mortality, quantity of blood and/or plasma products used, and relationship between preprocedural platelet count and periprocedural bleeding events.

The analysis showed that preprocedural INR was not significantly associated with periprocedural bleeding events (pooled odds ratio, 1.52; 95% confidence interval, 0.99-2.33; P = .06), a finding that held across INR threshold subgroups. Similarly, no significant difference was found between mean INR of patients who had bleeding events versus that of those who did not (pooled mean difference, 0.05; 95% CI, 0.03-0.13; P = .23).

Preprocedural platelet count was also a poor predictor of periprocedural bleeding, with a pooled odds ratio of 1.24 (95% CI, 0.55-2.77; P = .60), although the investigators noted that platelet count thresholds varied widely across studies, from 30 to 150 × 10⁹/L. When studies were stratified by procedural bleeding risk or procedure type, subgroup effects were no longer significant. Other secondary endpoints were incalculable because of insufficient data.

“Hopefully, these findings will spark initiation of more large-scale, higher-quality studies ... to reinforce minimizing administration of fresh frozen plasma for inappropriate correction of INR, which carries a multitude of adverse effects among cirrhotic [patients],” the investigators concluded.

According to Stephen H. Caldwell, MD, of the University of Virginia in Charlottesville, “The present paper augments accumulating literature over the past 15 years that INR should be discarded as a measure of procedure-related bleeding risk.”

Dr. Caldwell pointed out that “bleeding in cirrhosis is usually related to portal hypertension not with impaired hemostasis, with the occasional exception of hyperfibrinolysis, which is very different from a prolonged INR.”

He went on to suggest that the present findings should dissuade clinicians from a practice that, for some, is reflexive rather than evidence based.

“It’s remarkable how many medical practices become entrenched based on hand-me-down teaching during our early training years, and remain so for many years beyond as we disperse into various medical and surgical fields,” Dr. Caldwell said. “These learned approaches to common problems can clearly persist for generations despite overwhelming evidence to the contrary that usually evolve slowly and well-insulated within subspecialties or sub-subspecialties, and hence take several generations of training to diffuse into the wider practice of medical care for common problems. These may become matters of expedience in decision-making, much like the old antibiotic conundrum of ‘no-think-a-cillin,’ as critics referred to over-use of broad spectrum antibiotics. And so it has been with the INR.”The investigators disclosed relationships with AbbVie, Eisai, Gilead, and others. Dr. Caldwell disclosed research support from Daiichi concerning the potential role of anticoagulation therapy in preventing cirrhosis progression.

SOURCE: Kovalic AJ et al. Aliment Pharmacol Ther. 2020 Sep 10. doi: 10.1111/apt.16078.

International normalized ratio (INR) does not predict periprocedural bleeding in patients with cirrhosis, according to a meta-analysis of 29 studies.

This finding should deter the common practice of delivering blood products to cirrhotic patients with an elevated INR, reported lead author Alexander J. Kovalic, MD, of Novant Forsyth Medical Center in Winston Salem, N.C., and colleagues.

“INR measurement among cirrhotic patients is important in MELD [Model for End-Stage Liver Disease] prognostication and assessment of underlying hepatic synthetic function, however the INR alone does not capture the complicated interplay of anticoagulant and procoagulant deficiencies present in cirrhotic coagulopathy,” Dr. Kovalic and colleagues wrote in Alimentary Pharmacology & Therapeutics. “Yet, the ‘correction’ of these aberrancies among peripheral coagulation tests remains common ... even in modern practice, and not uncommonly occurs in the periprocedural setting.”

According to investigators, addressing INR with blood transfusion can have a litany of negative effects. Beyond the risks faced by all patient populations, increasing blood volume in those with cirrhosis can increase portal venous pressure, thereby raising risks of portal gastropathy or variceal hemorrhage. In addition, giving plasma products to patients with cirrhotic coagulopathy may further disrupt the balance between anticoagulants and procoagulants, potentially triggering disseminated intravascular coagulation.

Dr. Kovalic and colleagues noted that the lack of correlation between peripheral coagulation tests and bleeding risk has been a longstanding subject of investigation, citing studies from as early as 1981.

To add further weight to this body of evidence, the investigators conducted a systematic review and meta-analysis involving 13,276 patients with cirrhosis who underwent various procedures between 1999 and 2019. Primary outcomes included periprocedural bleeding events and the association between preprocedural INR and periprocedural bleeding events. Secondary outcomes included mortality, quantity of blood and/or plasma products used, and relationship between preprocedural platelet count and periprocedural bleeding events.

The analysis showed that preprocedural INR was not significantly associated with periprocedural bleeding events (pooled odds ratio, 1.52; 95% confidence interval, 0.99-2.33; P = .06), a finding that held across INR threshold subgroups. Similarly, no significant difference was found between mean INR of patients who had bleeding events versus that of those who did not (pooled mean difference, 0.05; 95% CI, 0.03-0.13; P = .23).

Preprocedural platelet count was also a poor predictor of periprocedural bleeding, with a pooled odds ratio of 1.24 (95% CI, 0.55-2.77; P = .60), although the investigators noted that platelet count thresholds varied widely across studies, from 30 to 150 × 10⁹/L. When studies were stratified by procedural bleeding risk or procedure type, subgroup effects were no longer significant. Other secondary endpoints were incalculable because of insufficient data.

“Hopefully, these findings will spark initiation of more large-scale, higher-quality studies ... to reinforce minimizing administration of fresh frozen plasma for inappropriate correction of INR, which carries a multitude of adverse effects among cirrhotic [patients],” the investigators concluded.

According to Stephen H. Caldwell, MD, of the University of Virginia in Charlottesville, “The present paper augments accumulating literature over the past 15 years that INR should be discarded as a measure of procedure-related bleeding risk.”

Dr. Caldwell pointed out that “bleeding in cirrhosis is usually related to portal hypertension not with impaired hemostasis, with the occasional exception of hyperfibrinolysis, which is very different from a prolonged INR.”

He went on to suggest that the present findings should dissuade clinicians from a practice that, for some, is reflexive rather than evidence based.

“It’s remarkable how many medical practices become entrenched based on hand-me-down teaching during our early training years, and remain so for many years beyond as we disperse into various medical and surgical fields,” Dr. Caldwell said. “These learned approaches to common problems can clearly persist for generations despite overwhelming evidence to the contrary that usually evolve slowly and well-insulated within subspecialties or sub-subspecialties, and hence take several generations of training to diffuse into the wider practice of medical care for common problems. These may become matters of expedience in decision-making, much like the old antibiotic conundrum of ‘no-think-a-cillin,’ as critics referred to over-use of broad spectrum antibiotics. And so it has been with the INR.”The investigators disclosed relationships with AbbVie, Eisai, Gilead, and others. Dr. Caldwell disclosed research support from Daiichi concerning the potential role of anticoagulation therapy in preventing cirrhosis progression.

SOURCE: Kovalic AJ et al. Aliment Pharmacol Ther. 2020 Sep 10. doi: 10.1111/apt.16078.

With high rates of fatty liver disease known to occur among people with type 2 diabetes, is it time to introduce routine liver screening into daily diabetes practice? The answer depends on whom you ask, and then there are still some important caveats.

Wavebreakmedia Ltd/ThinkStockPhotos.com

From the hepatologist’s perspective, there is no excuse not to consider liver surveillance now that noninvasive screening methods are available, suggested Michael Trauner, MD, of the Medical University of Vienna.

“From a practical standpoint, I think every type 2 diabetic over 50 years of age is at high risk,” and consequently should be screened at diagnosis, Dr. Trauner said during a debate at the virtual annual meeting of the European Association for the Study of Diabetes. “I would screen at diagnosis and then decide on recall depending on noninvasive fibrosis markers.”

“It’s a rising problem that we are facing these days,” observed Michael Roden, MD, chair and professor of internal medicine, endocrinology and metabolic diseases at Heinrich-Heine University in Düsseldorf, Germany, and who cochaired the session. Not only do people with type 2 diabetes have an increased risk for developing liver diseases, but also there’s a higher risk for those with fatty liver diseases developing type 2 diabetes.

A meta-analysis published in Gut in just last week illustrates just how big a problem this is – nonalcoholic fatty liver disease (NAFLD) “doubled the risk of type 2 diabetes,” said Dr Rosen, who is also the director of the division of endocrinology and diabetology at University Clinics Düsseldorf. That analysis was based on more than 500,000 people, almost 28,000 of whom had incident diabetes over a 5-year period.
 

Screening tools scarce

This makes liver screening in type 2 diabetes patients “a formidable challenge,” cautioned Gianluca Perseghin, MD, professor of endocrinology at the Monza (Italy) Polyclinic and the University of Milano-Bicocca in Milan.

“Hepatologists generally see only the most severe cases,” Dr. Perseghin said. Diabetologists and endocrinologists would be likely to see huge numbers of patients that could potentially be at risk for liver disease and following the recommendations set out in the joint European Association for the Study of the Liver/EASD/European Association for the Study of Obesity guidelines would result in a huge number of patients being identified and potentially needing referral, he argued.

“At this stage, we need to build friendly, reliable and cost-effective screening process to be applied in the health systems,” Dr. Perseghin suggested. He proposed that liver surveillance would need to be not only personalized on a patient level, but also at the infrastructure level. Measuring liver enzymes, for example, was going to be less accurate in picking up liver disease but blood tests were widely available, whereas imaging methods were not going to be something all diabetes clinics would have immediate access to.

“There are clearly a lot of provocative decisions still to be made,” acknowledged Philip Newsome, PhD, FRCPE, an honorary consultant hepatologist at the University of Birmingham (England) and who cochaired the debate.

“We need to demonstrate that looking for the presence of liver disease in this cohort changes their outcomes in a way that is cost effective,” Dr. Newsome, who is also the secretary general of EASL.

“Tests are evolving, but more importantly, treatments are evolving. So, the decision around cost effectiveness will clearly change,” he added.
 

NAFLD therapies unclar

“There are still a lot of questions,” Dr. Newsome said during a Novo-Nordisk–sponsored “Meet the Expert” session discussing EASL-EASD-EASO guidelines. “We don’t have any licensed therapies at the moment. But there’s been a huge amount of investment, looking at all sorts of different approaches.”

Dr. Newsome added: “We also don’t know how to monitor these patients. Most of the noninvasive are very useful for staging patients, but we don’t really understand how useful they are for monitoring changes in fibrosis.”

Diabetologist Hannele Yki-Järvinen, MD, PhD, of the University of Helsinki, gave her thoughts on the topic during the same session.

“We should add FIB-4 [Fibrosis-4 index] to the annual exam and ask the lab to calculate FIB-4 automatically,” Dr. Yki-Järvinen said. FIB-4is calculated using the patients age and the results of readily available blood tests that measure the AST/ALT ratio and the platelet count.

Dr. Trauner has received advisory fees and grant support from various companies with an interest in developing liver-directed therapies, and is also a coinventor of 24-norursodeoxycholic acid under development for cholestatic liver disease and potentially NAFLD. Dr. Perseghin has received honoraria and grant support from various pharmaceutical companies with an interest in diabetes care. Dr. Roden did not provide any disclosures. Dr. Newsome has received research grants from Boehringer Ingelheim and Novo Nordisk and acted as a consultant to many pharmaceutical companies. Dr. Yki-Järvinen disclosed receiving consultancy fees from Eli Lilly, MSD, and Novo Nordisk.

SOURCE: Trauner M; Persghin G. EASD 2020, Session S27.

With high rates of fatty liver disease known to occur among people with type 2 diabetes, is it time to introduce routine liver screening into daily diabetes practice? The answer depends on whom you ask, and then there are still some important caveats.

Wavebreakmedia Ltd/ThinkStockPhotos.com

From the hepatologist’s perspective, there is no excuse not to consider liver surveillance now that noninvasive screening methods are available, suggested Michael Trauner, MD, of the Medical University of Vienna.

“From a practical standpoint, I think every type 2 diabetic over 50 years of age is at high risk,” and consequently should be screened at diagnosis, Dr. Trauner said during a debate at the virtual annual meeting of the European Association for the Study of Diabetes. “I would screen at diagnosis and then decide on recall depending on noninvasive fibrosis markers.”

“It’s a rising problem that we are facing these days,” observed Michael Roden, MD, chair and professor of internal medicine, endocrinology and metabolic diseases at Heinrich-Heine University in Düsseldorf, Germany, and who cochaired the session. Not only do people with type 2 diabetes have an increased risk for developing liver diseases, but also there’s a higher risk for those with fatty liver diseases developing type 2 diabetes.

A meta-analysis published in Gut in just last week illustrates just how big a problem this is – nonalcoholic fatty liver disease (NAFLD) “doubled the risk of type 2 diabetes,” said Dr Rosen, who is also the director of the division of endocrinology and diabetology at University Clinics Düsseldorf. That analysis was based on more than 500,000 people, almost 28,000 of whom had incident diabetes over a 5-year period.
 

Screening tools scarce

This makes liver screening in type 2 diabetes patients “a formidable challenge,” cautioned Gianluca Perseghin, MD, professor of endocrinology at the Monza (Italy) Polyclinic and the University of Milano-Bicocca in Milan.

“Hepatologists generally see only the most severe cases,” Dr. Perseghin said. Diabetologists and endocrinologists would be likely to see huge numbers of patients that could potentially be at risk for liver disease and following the recommendations set out in the joint European Association for the Study of the Liver/EASD/European Association for the Study of Obesity guidelines would result in a huge number of patients being identified and potentially needing referral, he argued.

“At this stage, we need to build friendly, reliable and cost-effective screening process to be applied in the health systems,” Dr. Perseghin suggested. He proposed that liver surveillance would need to be not only personalized on a patient level, but also at the infrastructure level. Measuring liver enzymes, for example, was going to be less accurate in picking up liver disease but blood tests were widely available, whereas imaging methods were not going to be something all diabetes clinics would have immediate access to.

“There are clearly a lot of provocative decisions still to be made,” acknowledged Philip Newsome, PhD, FRCPE, an honorary consultant hepatologist at the University of Birmingham (England) and who cochaired the debate.

“We need to demonstrate that looking for the presence of liver disease in this cohort changes their outcomes in a way that is cost effective,” Dr. Newsome, who is also the secretary general of EASL.

“Tests are evolving, but more importantly, treatments are evolving. So, the decision around cost effectiveness will clearly change,” he added.
 

NAFLD therapies unclar

“There are still a lot of questions,” Dr. Newsome said during a Novo-Nordisk–sponsored “Meet the Expert” session discussing EASL-EASD-EASO guidelines. “We don’t have any licensed therapies at the moment. But there’s been a huge amount of investment, looking at all sorts of different approaches.”

Dr. Newsome added: “We also don’t know how to monitor these patients. Most of the noninvasive are very useful for staging patients, but we don’t really understand how useful they are for monitoring changes in fibrosis.”

Diabetologist Hannele Yki-Järvinen, MD, PhD, of the University of Helsinki, gave her thoughts on the topic during the same session.

“We should add FIB-4 [Fibrosis-4 index] to the annual exam and ask the lab to calculate FIB-4 automatically,” Dr. Yki-Järvinen said. FIB-4is calculated using the patients age and the results of readily available blood tests that measure the AST/ALT ratio and the platelet count.

Dr. Trauner has received advisory fees and grant support from various companies with an interest in developing liver-directed therapies, and is also a coinventor of 24-norursodeoxycholic acid under development for cholestatic liver disease and potentially NAFLD. Dr. Perseghin has received honoraria and grant support from various pharmaceutical companies with an interest in diabetes care. Dr. Roden did not provide any disclosures. Dr. Newsome has received research grants from Boehringer Ingelheim and Novo Nordisk and acted as a consultant to many pharmaceutical companies. Dr. Yki-Järvinen disclosed receiving consultancy fees from Eli Lilly, MSD, and Novo Nordisk.

SOURCE: Trauner M; Persghin G. EASD 2020, Session S27.

With high rates of fatty liver disease known to occur among people with type 2 diabetes, is it time to introduce routine liver screening into daily diabetes practice? The answer depends on whom you ask, and then there are still some important caveats.

Wavebreakmedia Ltd/ThinkStockPhotos.com

From the hepatologist’s perspective, there is no excuse not to consider liver surveillance now that noninvasive screening methods are available, suggested Michael Trauner, MD, of the Medical University of Vienna.

“From a practical standpoint, I think every type 2 diabetic over 50 years of age is at high risk,” and consequently should be screened at diagnosis, Dr. Trauner said during a debate at the virtual annual meeting of the European Association for the Study of Diabetes. “I would screen at diagnosis and then decide on recall depending on noninvasive fibrosis markers.”

“It’s a rising problem that we are facing these days,” observed Michael Roden, MD, chair and professor of internal medicine, endocrinology and metabolic diseases at Heinrich-Heine University in Düsseldorf, Germany, and who cochaired the session. Not only do people with type 2 diabetes have an increased risk for developing liver diseases, but also there’s a higher risk for those with fatty liver diseases developing type 2 diabetes.

A meta-analysis published in Gut in just last week illustrates just how big a problem this is – nonalcoholic fatty liver disease (NAFLD) “doubled the risk of type 2 diabetes,” said Dr Rosen, who is also the director of the division of endocrinology and diabetology at University Clinics Düsseldorf. That analysis was based on more than 500,000 people, almost 28,000 of whom had incident diabetes over a 5-year period.
 

Screening tools scarce

This makes liver screening in type 2 diabetes patients “a formidable challenge,” cautioned Gianluca Perseghin, MD, professor of endocrinology at the Monza (Italy) Polyclinic and the University of Milano-Bicocca in Milan.

“Hepatologists generally see only the most severe cases,” Dr. Perseghin said. Diabetologists and endocrinologists would be likely to see huge numbers of patients that could potentially be at risk for liver disease and following the recommendations set out in the joint European Association for the Study of the Liver/EASD/European Association for the Study of Obesity guidelines would result in a huge number of patients being identified and potentially needing referral, he argued.

“At this stage, we need to build friendly, reliable and cost-effective screening process to be applied in the health systems,” Dr. Perseghin suggested. He proposed that liver surveillance would need to be not only personalized on a patient level, but also at the infrastructure level. Measuring liver enzymes, for example, was going to be less accurate in picking up liver disease but blood tests were widely available, whereas imaging methods were not going to be something all diabetes clinics would have immediate access to.

“There are clearly a lot of provocative decisions still to be made,” acknowledged Philip Newsome, PhD, FRCPE, an honorary consultant hepatologist at the University of Birmingham (England) and who cochaired the debate.

“We need to demonstrate that looking for the presence of liver disease in this cohort changes their outcomes in a way that is cost effective,” Dr. Newsome, who is also the secretary general of EASL.

“Tests are evolving, but more importantly, treatments are evolving. So, the decision around cost effectiveness will clearly change,” he added.
 

NAFLD therapies unclar

“There are still a lot of questions,” Dr. Newsome said during a Novo-Nordisk–sponsored “Meet the Expert” session discussing EASL-EASD-EASO guidelines. “We don’t have any licensed therapies at the moment. But there’s been a huge amount of investment, looking at all sorts of different approaches.”

Dr. Newsome added: “We also don’t know how to monitor these patients. Most of the noninvasive are very useful for staging patients, but we don’t really understand how useful they are for monitoring changes in fibrosis.”

Diabetologist Hannele Yki-Järvinen, MD, PhD, of the University of Helsinki, gave her thoughts on the topic during the same session.

“We should add FIB-4 [Fibrosis-4 index] to the annual exam and ask the lab to calculate FIB-4 automatically,” Dr. Yki-Järvinen said. FIB-4is calculated using the patients age and the results of readily available blood tests that measure the AST/ALT ratio and the platelet count.

Dr. Trauner has received advisory fees and grant support from various companies with an interest in developing liver-directed therapies, and is also a coinventor of 24-norursodeoxycholic acid under development for cholestatic liver disease and potentially NAFLD. Dr. Perseghin has received honoraria and grant support from various pharmaceutical companies with an interest in diabetes care. Dr. Roden did not provide any disclosures. Dr. Newsome has received research grants from Boehringer Ingelheim and Novo Nordisk and acted as a consultant to many pharmaceutical companies. Dr. Yki-Järvinen disclosed receiving consultancy fees from Eli Lilly, MSD, and Novo Nordisk.

SOURCE: Trauner M; Persghin G. EASD 2020, Session S27.

Not only the prevalence, but the impact of nonalcoholic fatty liver disease (NAFLD) is increasing in much of the world, Arun J. Sanyal, MD, said in a virtual presentation at the meeting jointly provided by Rutgers and Global Academy for Medical Education. “It is currently estimated that the number of people living with cirrhosis or with decompensated cirrhosis will increase two- to threefold from 2015 to 2030,” which underlines the public health impact and the need for improved treatment paradigms, he emphasized.

“The thing to remember about NAFLD is that it does not exist in a vacuum,” Dr. Sanyal said. NAFLD is a multisystem disorder. Most patients have concomitant cardiovascular disease, but others may have type 2 diabetes, hypertension, and dyslipidemia, all of which are now accepted as risk factors for nonalcoholic steatohepatitis (NASH), he said.

“What ties these conditions together is metabolic stress leading to systemic inflammation and fibrosis. This is primarily due to diet-induced obesity. If you think about treating all of these competing risks to the patient’s life, the optimal way is to treat the root cause,” he said.

Various options exist to manage the conditions that can lead to NASH, but several of these also appear promising as a treatment of NASH, Dr. Sanyal said. Glucagonlike peptide–1 agonists and sodium-glucose transporter 2 inhibitors have been shown to improve multiple outcomes of interest in type 2 diabetes. However, insulin can cause weight gain at the expense of controlling HbA1C levels, he said.

Bariatric surgery can improve histology, but many patients with advanced fibrosis do not demonstrate improvement in fibrosis. Also, bariatric surgery has its own associated morbidity, including an increased suicide rate across multiple studies, Dr. Sanyal noted.

A new and interesting option is duodenal mucosal resurfacing (DMR) “a novel, minimally invasive outpatient upper-endoscopic procedure,” said Dr. Sanyal. DMR involves use of a catheter to perform a submucosal lift and hydrothermal mucosal ablation, prompting healthy epithelial regrowth, he explained. “The mucosa sloughs off, fresh epithelium grows in, and the hormonal signal from the gut to the rest of the body is restored to a more normal pattern,” he noted.

In the REVITA-2 study of patients with diabetes and NAFLD, the average fat loss was 5.4% in those randomized to DMR vs. 2.4% in sham-procedure patients and represented “quite significant defatting of the liver,” Dr. Sanyal said.

Dr. Sanyal then focused on fatty liver disease. “The first step when you see a patient with fatty liver disease is to see how scarred is the liver, and whether the patient has silent cirrhosis. The more scarred the liver, the greater risk of liver-related outcomes,” he said. The goal of therapy for these patients is to reduce the risk of progression to cirrhosis, he added. Dr. Sanyal recommended evaluating fibrosis using the Fibrosis 4 score (Fib4). “If the Fib4 is less than 1.3, the likelihood of significant scarring in the liver is less than 10%,” he said. On the other hand, a Fib4 greater than 2.67 suggests advanced fibrosis, he noted.

Overall, the goals of treatment for NASH patients are to prevent cirrhosis, reduce decompensation, and prevent hepatocellular carcinoma, said Dr. Sanyal.

“The ideal drug for NASH should also help other end organs, or at least be neutral,” said Dr. Sanyal.

Current frontline therapies for precirrhotic NASH include thiazolidinediones (TZD), farnesoid X receptor (FXR)/fibroblast growth factor 19 (FGF-19), FGF21, thyroxine B-R, and glucagonlike peptide-1. Clinical evidence varies based on different populations, endpoints, assessment methods, and treatment duration, he said.

Looking ahead to the next decade, a NASH management paradigm will likely play out that can be applied in the clinic today, Dr. Sanyal said. First, make an initial assessment of the status of the end organs. Start with a weight-loss regimen; use statins and GLP-1 and SGLT2 inhibitors as needed. Follow and reassess, and if the patient still has disease, progress to targeted therapy for active NASH while continuing to encourage weight loss and healthy living, he said.

“The ultimate proof that what we are doing is working is that we are improving mortality, reducing health care costs, and improving patients’ function and quality of life,” he concluded.

Dr. Sanyal is president of Sanyal Biotechnologies. He also disclosed stock options for Durect, Exhalenz, Galmed, Genfit, Immuton, Indalo, and Tiziana, as well as various relationships with Allergan, AMRA, Astra Zeneca-Medimmune, Birdrock, Boehringer Ingelheim, Bristol Myers, Echosense, GE, Genentech, Gilead, Hemoshear, IFMO, Innovate, Intercept, Lilly, Lipocine, Merck, Novartis, Novo Nordisk, OWL, Pfizer, RedX, Sundise, Tern, and Zydus.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Help your patients understand their risks for NASH by sharing AGA patient education at http://ow.ly/5AAk30rbK5y.

Not only the prevalence, but the impact of nonalcoholic fatty liver disease (NAFLD) is increasing in much of the world, Arun J. Sanyal, MD, said in a virtual presentation at the meeting jointly provided by Rutgers and Global Academy for Medical Education. “It is currently estimated that the number of people living with cirrhosis or with decompensated cirrhosis will increase two- to threefold from 2015 to 2030,” which underlines the public health impact and the need for improved treatment paradigms, he emphasized.

“The thing to remember about NAFLD is that it does not exist in a vacuum,” Dr. Sanyal said. NAFLD is a multisystem disorder. Most patients have concomitant cardiovascular disease, but others may have type 2 diabetes, hypertension, and dyslipidemia, all of which are now accepted as risk factors for nonalcoholic steatohepatitis (NASH), he said.

“What ties these conditions together is metabolic stress leading to systemic inflammation and fibrosis. This is primarily due to diet-induced obesity. If you think about treating all of these competing risks to the patient’s life, the optimal way is to treat the root cause,” he said.

Various options exist to manage the conditions that can lead to NASH, but several of these also appear promising as a treatment of NASH, Dr. Sanyal said. Glucagonlike peptide–1 agonists and sodium-glucose transporter 2 inhibitors have been shown to improve multiple outcomes of interest in type 2 diabetes. However, insulin can cause weight gain at the expense of controlling HbA1C levels, he said.

Bariatric surgery can improve histology, but many patients with advanced fibrosis do not demonstrate improvement in fibrosis. Also, bariatric surgery has its own associated morbidity, including an increased suicide rate across multiple studies, Dr. Sanyal noted.

A new and interesting option is duodenal mucosal resurfacing (DMR) “a novel, minimally invasive outpatient upper-endoscopic procedure,” said Dr. Sanyal. DMR involves use of a catheter to perform a submucosal lift and hydrothermal mucosal ablation, prompting healthy epithelial regrowth, he explained. “The mucosa sloughs off, fresh epithelium grows in, and the hormonal signal from the gut to the rest of the body is restored to a more normal pattern,” he noted.

In the REVITA-2 study of patients with diabetes and NAFLD, the average fat loss was 5.4% in those randomized to DMR vs. 2.4% in sham-procedure patients and represented “quite significant defatting of the liver,” Dr. Sanyal said.

Dr. Sanyal then focused on fatty liver disease. “The first step when you see a patient with fatty liver disease is to see how scarred is the liver, and whether the patient has silent cirrhosis. The more scarred the liver, the greater risk of liver-related outcomes,” he said. The goal of therapy for these patients is to reduce the risk of progression to cirrhosis, he added. Dr. Sanyal recommended evaluating fibrosis using the Fibrosis 4 score (Fib4). “If the Fib4 is less than 1.3, the likelihood of significant scarring in the liver is less than 10%,” he said. On the other hand, a Fib4 greater than 2.67 suggests advanced fibrosis, he noted.

Overall, the goals of treatment for NASH patients are to prevent cirrhosis, reduce decompensation, and prevent hepatocellular carcinoma, said Dr. Sanyal.

“The ideal drug for NASH should also help other end organs, or at least be neutral,” said Dr. Sanyal.

Current frontline therapies for precirrhotic NASH include thiazolidinediones (TZD), farnesoid X receptor (FXR)/fibroblast growth factor 19 (FGF-19), FGF21, thyroxine B-R, and glucagonlike peptide-1. Clinical evidence varies based on different populations, endpoints, assessment methods, and treatment duration, he said.

Looking ahead to the next decade, a NASH management paradigm will likely play out that can be applied in the clinic today, Dr. Sanyal said. First, make an initial assessment of the status of the end organs. Start with a weight-loss regimen; use statins and GLP-1 and SGLT2 inhibitors as needed. Follow and reassess, and if the patient still has disease, progress to targeted therapy for active NASH while continuing to encourage weight loss and healthy living, he said.

“The ultimate proof that what we are doing is working is that we are improving mortality, reducing health care costs, and improving patients’ function and quality of life,” he concluded.

Dr. Sanyal is president of Sanyal Biotechnologies. He also disclosed stock options for Durect, Exhalenz, Galmed, Genfit, Immuton, Indalo, and Tiziana, as well as various relationships with Allergan, AMRA, Astra Zeneca-Medimmune, Birdrock, Boehringer Ingelheim, Bristol Myers, Echosense, GE, Genentech, Gilead, Hemoshear, IFMO, Innovate, Intercept, Lilly, Lipocine, Merck, Novartis, Novo Nordisk, OWL, Pfizer, RedX, Sundise, Tern, and Zydus.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Help your patients understand their risks for NASH by sharing AGA patient education at http://ow.ly/5AAk30rbK5y.

Not only the prevalence, but the impact of nonalcoholic fatty liver disease (NAFLD) is increasing in much of the world, Arun J. Sanyal, MD, said in a virtual presentation at the meeting jointly provided by Rutgers and Global Academy for Medical Education. “It is currently estimated that the number of people living with cirrhosis or with decompensated cirrhosis will increase two- to threefold from 2015 to 2030,” which underlines the public health impact and the need for improved treatment paradigms, he emphasized.

“The thing to remember about NAFLD is that it does not exist in a vacuum,” Dr. Sanyal said. NAFLD is a multisystem disorder. Most patients have concomitant cardiovascular disease, but others may have type 2 diabetes, hypertension, and dyslipidemia, all of which are now accepted as risk factors for nonalcoholic steatohepatitis (NASH), he said.

“What ties these conditions together is metabolic stress leading to systemic inflammation and fibrosis. This is primarily due to diet-induced obesity. If you think about treating all of these competing risks to the patient’s life, the optimal way is to treat the root cause,” he said.

Various options exist to manage the conditions that can lead to NASH, but several of these also appear promising as a treatment of NASH, Dr. Sanyal said. Glucagonlike peptide–1 agonists and sodium-glucose transporter 2 inhibitors have been shown to improve multiple outcomes of interest in type 2 diabetes. However, insulin can cause weight gain at the expense of controlling HbA1C levels, he said.

Bariatric surgery can improve histology, but many patients with advanced fibrosis do not demonstrate improvement in fibrosis. Also, bariatric surgery has its own associated morbidity, including an increased suicide rate across multiple studies, Dr. Sanyal noted.

A new and interesting option is duodenal mucosal resurfacing (DMR) “a novel, minimally invasive outpatient upper-endoscopic procedure,” said Dr. Sanyal. DMR involves use of a catheter to perform a submucosal lift and hydrothermal mucosal ablation, prompting healthy epithelial regrowth, he explained. “The mucosa sloughs off, fresh epithelium grows in, and the hormonal signal from the gut to the rest of the body is restored to a more normal pattern,” he noted.

In the REVITA-2 study of patients with diabetes and NAFLD, the average fat loss was 5.4% in those randomized to DMR vs. 2.4% in sham-procedure patients and represented “quite significant defatting of the liver,” Dr. Sanyal said.

Dr. Sanyal then focused on fatty liver disease. “The first step when you see a patient with fatty liver disease is to see how scarred is the liver, and whether the patient has silent cirrhosis. The more scarred the liver, the greater risk of liver-related outcomes,” he said. The goal of therapy for these patients is to reduce the risk of progression to cirrhosis, he added. Dr. Sanyal recommended evaluating fibrosis using the Fibrosis 4 score (Fib4). “If the Fib4 is less than 1.3, the likelihood of significant scarring in the liver is less than 10%,” he said. On the other hand, a Fib4 greater than 2.67 suggests advanced fibrosis, he noted.

Overall, the goals of treatment for NASH patients are to prevent cirrhosis, reduce decompensation, and prevent hepatocellular carcinoma, said Dr. Sanyal.

“The ideal drug for NASH should also help other end organs, or at least be neutral,” said Dr. Sanyal.

Current frontline therapies for precirrhotic NASH include thiazolidinediones (TZD), farnesoid X receptor (FXR)/fibroblast growth factor 19 (FGF-19), FGF21, thyroxine B-R, and glucagonlike peptide-1. Clinical evidence varies based on different populations, endpoints, assessment methods, and treatment duration, he said.

Looking ahead to the next decade, a NASH management paradigm will likely play out that can be applied in the clinic today, Dr. Sanyal said. First, make an initial assessment of the status of the end organs. Start with a weight-loss regimen; use statins and GLP-1 and SGLT2 inhibitors as needed. Follow and reassess, and if the patient still has disease, progress to targeted therapy for active NASH while continuing to encourage weight loss and healthy living, he said.

“The ultimate proof that what we are doing is working is that we are improving mortality, reducing health care costs, and improving patients’ function and quality of life,” he concluded.

Dr. Sanyal is president of Sanyal Biotechnologies. He also disclosed stock options for Durect, Exhalenz, Galmed, Genfit, Immuton, Indalo, and Tiziana, as well as various relationships with Allergan, AMRA, Astra Zeneca-Medimmune, Birdrock, Boehringer Ingelheim, Bristol Myers, Echosense, GE, Genentech, Gilead, Hemoshear, IFMO, Innovate, Intercept, Lilly, Lipocine, Merck, Novartis, Novo Nordisk, OWL, Pfizer, RedX, Sundise, Tern, and Zydus.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Help your patients understand their risks for NASH by sharing AGA patient education at http://ow.ly/5AAk30rbK5y.

Rates of hepatocellular carcinoma (HCC) continue to rise in the United States, but unevenly so given how the incidence has become highest in the Hispanic population, which is reflected in increased rates in the southern and western states, Hashem B. El-Serag, MD, of Baylor College of Medicine, Houston, said in a virtual presentation at the annual Digestive Diseases: New Advances, which is jointly provided by Rutgers and Global Academy for Medical Education.

In addition to this demographic shift, the risk factors for HCC are shifting, he said. Hepatitis C virus (HCV) has been the dominant risk factor for HCC; for patients with active HCV, the factors historically associated with increased HCC risk have included alcohol consumption, obesity, diabetes, coinfection, and genetics, he said.

This pattern is starting to change. In fact, for patients with active HCV, antiviral treatment with a sustained virologic response has surfaced as the most significant risk factor in the development of HCC, said Dr. El-Serag: Among these patients, sustained virologic response from direct-acting antivirals is associated with a significant reduction in HCC risk. However, it is important to recognize that a residual risk of HCC remains that doesn’t go away for several years, he noted.

“Who are those people who got treated, got cured, and still developed HCC? Those with cirrhosis at the time of treatment,” he said. Those with cirrhosis have cumulative incidence of 1.8% per year, but those without cirrhosis had very low risk, he said.

Some good news in HCC is that rates appear to be declining among young men, and this is thought to be one of the groups who are achieving a cure of HCV, he said.

“One would hope, if goals for HCV elimination are met, that will translate into massive reduction of HCC,” he said.

“The issue now for hepatitis is finding infected patients and curing them,” he noted.

Dr. El-Serag touched on hepatitis B (HBV), which continues to be the driving force of hepatitis infections globally. However, in patients who receive and respond to antiviral treatment “there is a significant and considerable reduction in HCC in the context of hepatitis B” similar to that seen with hepatitis C. Vaccination programs for HBV have started to make the desired impact of reducing HCC in HBV-endemic areas, he noted.

However, current risk factors for HCC are related less to HCV and HBV and more to metabolic syndrome because more people are treated for HCV and HBV, Dr. El-Serag said. He went on to address the new dominant global risk factor for HCC: obesity. Based on data from multiple studies, those who are obese, defined as a body mass index greater than 30 kg/m², carry a twofold increased risk of developing HCC, he said.

To reduce this risk, treatment targets might address intermediate factors such as abdominal obesity, said Dr. El-Serag. He cited a study published in Hepatology in which individuals in the highest tertile for waist-hip ratio had a threefold higher risk of HCC, compared with those in the lowest tertile.

In addition, consideration of obesity must include type 2 diabetes, which is often linked to obesity and occurs in approximately one-third of adults in the United States, Dr. El-Serag said.

Treatment of type 2 diabetes may make a difference in HCC risk reduction, Dr. El-Serag noted. “The impact of treatment of diabetes on HCC risk is an area of intense interest,” he said. Based on the latest research, “the bottom line is that those treated with metformin experience a 50% reduction in the risk of HCC,” he said

Dr. El-Serag also acknowledged the impact of other risk factors for HCC: the use of statins and the presence of nonalcoholic fatty liver disease (NAFLD).

Dr. El-Serag noted that, among NAFLD patients, subgroups at even greater risk for HCC include those with diabetes, those older than 65 years, Hispanic race, and those with cirrhosis. These patients should be candidates for surveillance. Metabolic dysfunction traits such as obesity and diabetes are very common conditions, so it’s important to look at other, more specific factors, he added. “I hope that there will be tools to help clinicians classify or risk-stratify patients into different buckets,” he said.

Areas for further research on HCC continue to include risk stratification, mechanisms of action, and HCC prevention related to treatment of metabolic syndrome, he emphasized.

Dr. El-Serag had no financial conflicts to disclose. Global Academy for Medical Education and this news organization are owned by the same parent company.

*This story was updated on Oct. 28, 2020. 

SOURCE: El-Serag HB. Digestive Diseases: New Advances 2020.

Rates of hepatocellular carcinoma (HCC) continue to rise in the United States, but unevenly so given how the incidence has become highest in the Hispanic population, which is reflected in increased rates in the southern and western states, Hashem B. El-Serag, MD, of Baylor College of Medicine, Houston, said in a virtual presentation at the annual Digestive Diseases: New Advances, which is jointly provided by Rutgers and Global Academy for Medical Education.

In addition to this demographic shift, the risk factors for HCC are shifting, he said. Hepatitis C virus (HCV) has been the dominant risk factor for HCC; for patients with active HCV, the factors historically associated with increased HCC risk have included alcohol consumption, obesity, diabetes, coinfection, and genetics, he said.

This pattern is starting to change. In fact, for patients with active HCV, antiviral treatment with a sustained virologic response has surfaced as the most significant risk factor in the development of HCC, said Dr. El-Serag: Among these patients, sustained virologic response from direct-acting antivirals is associated with a significant reduction in HCC risk. However, it is important to recognize that a residual risk of HCC remains that doesn’t go away for several years, he noted.

“Who are those people who got treated, got cured, and still developed HCC? Those with cirrhosis at the time of treatment,” he said. Those with cirrhosis have cumulative incidence of 1.8% per year, but those without cirrhosis had very low risk, he said.

Some good news in HCC is that rates appear to be declining among young men, and this is thought to be one of the groups who are achieving a cure of HCV, he said.

“One would hope, if goals for HCV elimination are met, that will translate into massive reduction of HCC,” he said.

“The issue now for hepatitis is finding infected patients and curing them,” he noted.

Dr. El-Serag touched on hepatitis B (HBV), which continues to be the driving force of hepatitis infections globally. However, in patients who receive and respond to antiviral treatment “there is a significant and considerable reduction in HCC in the context of hepatitis B” similar to that seen with hepatitis C. Vaccination programs for HBV have started to make the desired impact of reducing HCC in HBV-endemic areas, he noted.

However, current risk factors for HCC are related less to HCV and HBV and more to metabolic syndrome because more people are treated for HCV and HBV, Dr. El-Serag said. He went on to address the new dominant global risk factor for HCC: obesity. Based on data from multiple studies, those who are obese, defined as a body mass index greater than 30 kg/m², carry a twofold increased risk of developing HCC, he said.

To reduce this risk, treatment targets might address intermediate factors such as abdominal obesity, said Dr. El-Serag. He cited a study published in Hepatology in which individuals in the highest tertile for waist-hip ratio had a threefold higher risk of HCC, compared with those in the lowest tertile.

In addition, consideration of obesity must include type 2 diabetes, which is often linked to obesity and occurs in approximately one-third of adults in the United States, Dr. El-Serag said.

Treatment of type 2 diabetes may make a difference in HCC risk reduction, Dr. El-Serag noted. “The impact of treatment of diabetes on HCC risk is an area of intense interest,” he said. Based on the latest research, “the bottom line is that those treated with metformin experience a 50% reduction in the risk of HCC,” he said

Dr. El-Serag also acknowledged the impact of other risk factors for HCC: the use of statins and the presence of nonalcoholic fatty liver disease (NAFLD).

Dr. El-Serag noted that, among NAFLD patients, subgroups at even greater risk for HCC include those with diabetes, those older than 65 years, Hispanic race, and those with cirrhosis. These patients should be candidates for surveillance. Metabolic dysfunction traits such as obesity and diabetes are very common conditions, so it’s important to look at other, more specific factors, he added. “I hope that there will be tools to help clinicians classify or risk-stratify patients into different buckets,” he said.

Areas for further research on HCC continue to include risk stratification, mechanisms of action, and HCC prevention related to treatment of metabolic syndrome, he emphasized.

Dr. El-Serag had no financial conflicts to disclose. Global Academy for Medical Education and this news organization are owned by the same parent company.

*This story was updated on Oct. 28, 2020. 

SOURCE: El-Serag HB. Digestive Diseases: New Advances 2020.

Rates of hepatocellular carcinoma (HCC) continue to rise in the United States, but unevenly so given how the incidence has become highest in the Hispanic population, which is reflected in increased rates in the southern and western states, Hashem B. El-Serag, MD, of Baylor College of Medicine, Houston, said in a virtual presentation at the annual Digestive Diseases: New Advances, which is jointly provided by Rutgers and Global Academy for Medical Education.

In addition to this demographic shift, the risk factors for HCC are shifting, he said. Hepatitis C virus (HCV) has been the dominant risk factor for HCC; for patients with active HCV, the factors historically associated with increased HCC risk have included alcohol consumption, obesity, diabetes, coinfection, and genetics, he said.

This pattern is starting to change. In fact, for patients with active HCV, antiviral treatment with a sustained virologic response has surfaced as the most significant risk factor in the development of HCC, said Dr. El-Serag: Among these patients, sustained virologic response from direct-acting antivirals is associated with a significant reduction in HCC risk. However, it is important to recognize that a residual risk of HCC remains that doesn’t go away for several years, he noted.

“Who are those people who got treated, got cured, and still developed HCC? Those with cirrhosis at the time of treatment,” he said. Those with cirrhosis have cumulative incidence of 1.8% per year, but those without cirrhosis had very low risk, he said.

Some good news in HCC is that rates appear to be declining among young men, and this is thought to be one of the groups who are achieving a cure of HCV, he said.

“One would hope, if goals for HCV elimination are met, that will translate into massive reduction of HCC,” he said.

“The issue now for hepatitis is finding infected patients and curing them,” he noted.

Dr. El-Serag touched on hepatitis B (HBV), which continues to be the driving force of hepatitis infections globally. However, in patients who receive and respond to antiviral treatment “there is a significant and considerable reduction in HCC in the context of hepatitis B” similar to that seen with hepatitis C. Vaccination programs for HBV have started to make the desired impact of reducing HCC in HBV-endemic areas, he noted.

However, current risk factors for HCC are related less to HCV and HBV and more to metabolic syndrome because more people are treated for HCV and HBV, Dr. El-Serag said. He went on to address the new dominant global risk factor for HCC: obesity. Based on data from multiple studies, those who are obese, defined as a body mass index greater than 30 kg/m², carry a twofold increased risk of developing HCC, he said.

To reduce this risk, treatment targets might address intermediate factors such as abdominal obesity, said Dr. El-Serag. He cited a study published in Hepatology in which individuals in the highest tertile for waist-hip ratio had a threefold higher risk of HCC, compared with those in the lowest tertile.

In addition, consideration of obesity must include type 2 diabetes, which is often linked to obesity and occurs in approximately one-third of adults in the United States, Dr. El-Serag said.

Treatment of type 2 diabetes may make a difference in HCC risk reduction, Dr. El-Serag noted. “The impact of treatment of diabetes on HCC risk is an area of intense interest,” he said. Based on the latest research, “the bottom line is that those treated with metformin experience a 50% reduction in the risk of HCC,” he said

Dr. El-Serag also acknowledged the impact of other risk factors for HCC: the use of statins and the presence of nonalcoholic fatty liver disease (NAFLD).

Dr. El-Serag noted that, among NAFLD patients, subgroups at even greater risk for HCC include those with diabetes, those older than 65 years, Hispanic race, and those with cirrhosis. These patients should be candidates for surveillance. Metabolic dysfunction traits such as obesity and diabetes are very common conditions, so it’s important to look at other, more specific factors, he added. “I hope that there will be tools to help clinicians classify or risk-stratify patients into different buckets,” he said.

Areas for further research on HCC continue to include risk stratification, mechanisms of action, and HCC prevention related to treatment of metabolic syndrome, he emphasized.

Dr. El-Serag had no financial conflicts to disclose. Global Academy for Medical Education and this news organization are owned by the same parent company.

*This story was updated on Oct. 28, 2020. 

SOURCE: El-Serag HB. Digestive Diseases: New Advances 2020.

For patients with severe thrombocytopenia and chronic liver diseases, including hepatocellular carcinoma, treatment with lusutrombopag prior to invasive procedures significantly decreased the need for platelet transfusions without increasing the need for rescue treatment for bleeding or the rate of thromboembolic events.

In a post hoc analysis of data from 270 patients in two manufacturer-sponsored, multicenter, randomized, double-blind, placebo-controlled, phase 3 trials, significantly more lusutrombopag recipients met the primary efficacy endpoint, including patients with hepatocellular carcinoma (68.0% vs. 8.9% in the placebo group; P < .0001) and those without it (77.0% vs. 21.6%; P < .0001). Rates of treatment-emergent adverse events were similar between the lusutrombopag and placebo groups, and patients with hepatocellular carcinoma were not at increased risk for thrombosis, Naim Alkhouri, MD, of Texas Liver Institute in San Antonio, and associates wrote in Clinical Gastroenterology and Hepatology.

Platelet transfusion is the treatment mainstay for patients with thrombocytopenia related to cirrhosis who are undergoing invasive procedures, but its effects are short-lived, and at least one in five transfusions fails. Thrombopoietin agonists such as lusutrombopag are efficacious and approved in this setting, but they can be prothrombotic, particularly in patients with hepatocellular carcinoma, who already are at heightened risk for portal vein thrombosis.

Dr. Alkhouri and associates performed an integrated analysis of the PLUS 1 trial (Japan, October 2013–May 2014) and the L-PLUS 2 (global, June 2015–April 2017). Participants were adults with Child-Pugh Class A or B chronic liver disease and baseline platelet counts under 50 x 10⁹ per L who were scheduled for invasive procedures. Of the 270 patients, 95 had hepatocellular carcinoma. Patients were randomly assigned on a one-to-one basis to receive either lusutrombopag (3 mg) or placebo daily for up to 7 days before procedures. The primary endpoint was the percentage of patients in the per-protocol population who did not need a platelet transfusion before the invasive procedure or rescue therapy within 7 days afterward.

The treatment and placebo arms were similar except that patients with hepatocellular carcinoma were about 10 years older on average. In patients with hepatocellular carcinoma, 60.5% more lusutrombopag recipients than placebo recipients met the primary endpoint, and rates of bleeding-related adverse events were 9.1% and 15.7%, respectively. In patients with other chronic liver diseases, 52.6% more lusutrombopag recipients met the primary endpoint. Rates of bleeding-related adverse events were 5% and 10.6%.

“Approximately 88% of patients with hepatocellular carcinoma underwent a liver-related procedure, compared with approximately 10% of patients without hepatocellular carcinoma,” the investigators wrote. “This is significant because ablations or transcatheter arterial chemoembolizations can be associated with serious bleeding complications. It is clinically important that, given the greater number of liver-related procedures, the incidence of bleeding-related adverse events was lower in patients treated with lusutrombopag than placebo.”

Imaging after the procedures confirmed low rates of thromboses in both groups and subgroups. Four patients developed portal vein thromboses, including two lusutrombopag recipients (one of whom had hepatocellular carcinoma) and two placebo recipients without hepatocellular carcinoma.

These trials excluded patients undergoing major surgical procedures and those with decompensated cirrhosis; portal vein thrombosis; hematopoietic tumors; aplastic anemia; myelodysplastic syndrome; myelofibrosis; liver transplantation; splenectomy; and thrombocytopenia that was congenital, autoimmune, or drug induced. “A limitation of this study was the high rate of protocol violations related to platelet transfusions,” the researchers noted. “A number of patients [42 in all] were excluded from the per-protocol population owing to receipt of unnecessary platelet transfusions, or because they did not receive a needed platelet transfusion.”Shionogi makes lusutrombopag and sponsored the study. Dr. Alkhouri reported an advisory relationship with Shionogi and Dova Pharma. Two coinvestigators reported being employed by Shionogi. Three coinvestigators also disclosed ties to Shionogi and to several other pharmaceutical companies.

SOURCE: Alkhouri N et al. Clin Gastroenterol Hepatol. 2020 Mar 20. doi: 10.1016/j.cgh.2020.03.032.

For patients with severe thrombocytopenia and chronic liver diseases, including hepatocellular carcinoma, treatment with lusutrombopag prior to invasive procedures significantly decreased the need for platelet transfusions without increasing the need for rescue treatment for bleeding or the rate of thromboembolic events.

In a post hoc analysis of data from 270 patients in two manufacturer-sponsored, multicenter, randomized, double-blind, placebo-controlled, phase 3 trials, significantly more lusutrombopag recipients met the primary efficacy endpoint, including patients with hepatocellular carcinoma (68.0% vs. 8.9% in the placebo group; P < .0001) and those without it (77.0% vs. 21.6%; P < .0001). Rates of treatment-emergent adverse events were similar between the lusutrombopag and placebo groups, and patients with hepatocellular carcinoma were not at increased risk for thrombosis, Naim Alkhouri, MD, of Texas Liver Institute in San Antonio, and associates wrote in Clinical Gastroenterology and Hepatology.

Platelet transfusion is the treatment mainstay for patients with thrombocytopenia related to cirrhosis who are undergoing invasive procedures, but its effects are short-lived, and at least one in five transfusions fails. Thrombopoietin agonists such as lusutrombopag are efficacious and approved in this setting, but they can be prothrombotic, particularly in patients with hepatocellular carcinoma, who already are at heightened risk for portal vein thrombosis.

Dr. Alkhouri and associates performed an integrated analysis of the PLUS 1 trial (Japan, October 2013–May 2014) and the L-PLUS 2 (global, June 2015–April 2017). Participants were adults with Child-Pugh Class A or B chronic liver disease and baseline platelet counts under 50 x 10⁹ per L who were scheduled for invasive procedures. Of the 270 patients, 95 had hepatocellular carcinoma. Patients were randomly assigned on a one-to-one basis to receive either lusutrombopag (3 mg) or placebo daily for up to 7 days before procedures. The primary endpoint was the percentage of patients in the per-protocol population who did not need a platelet transfusion before the invasive procedure or rescue therapy within 7 days afterward.

The treatment and placebo arms were similar except that patients with hepatocellular carcinoma were about 10 years older on average. In patients with hepatocellular carcinoma, 60.5% more lusutrombopag recipients than placebo recipients met the primary endpoint, and rates of bleeding-related adverse events were 9.1% and 15.7%, respectively. In patients with other chronic liver diseases, 52.6% more lusutrombopag recipients met the primary endpoint. Rates of bleeding-related adverse events were 5% and 10.6%.

“Approximately 88% of patients with hepatocellular carcinoma underwent a liver-related procedure, compared with approximately 10% of patients without hepatocellular carcinoma,” the investigators wrote. “This is significant because ablations or transcatheter arterial chemoembolizations can be associated with serious bleeding complications. It is clinically important that, given the greater number of liver-related procedures, the incidence of bleeding-related adverse events was lower in patients treated with lusutrombopag than placebo.”

Imaging after the procedures confirmed low rates of thromboses in both groups and subgroups. Four patients developed portal vein thromboses, including two lusutrombopag recipients (one of whom had hepatocellular carcinoma) and two placebo recipients without hepatocellular carcinoma.

These trials excluded patients undergoing major surgical procedures and those with decompensated cirrhosis; portal vein thrombosis; hematopoietic tumors; aplastic anemia; myelodysplastic syndrome; myelofibrosis; liver transplantation; splenectomy; and thrombocytopenia that was congenital, autoimmune, or drug induced. “A limitation of this study was the high rate of protocol violations related to platelet transfusions,” the researchers noted. “A number of patients [42 in all] were excluded from the per-protocol population owing to receipt of unnecessary platelet transfusions, or because they did not receive a needed platelet transfusion.”Shionogi makes lusutrombopag and sponsored the study. Dr. Alkhouri reported an advisory relationship with Shionogi and Dova Pharma. Two coinvestigators reported being employed by Shionogi. Three coinvestigators also disclosed ties to Shionogi and to several other pharmaceutical companies.

SOURCE: Alkhouri N et al. Clin Gastroenterol Hepatol. 2020 Mar 20. doi: 10.1016/j.cgh.2020.03.032.

For patients with severe thrombocytopenia and chronic liver diseases, including hepatocellular carcinoma, treatment with lusutrombopag prior to invasive procedures significantly decreased the need for platelet transfusions without increasing the need for rescue treatment for bleeding or the rate of thromboembolic events.

In a post hoc analysis of data from 270 patients in two manufacturer-sponsored, multicenter, randomized, double-blind, placebo-controlled, phase 3 trials, significantly more lusutrombopag recipients met the primary efficacy endpoint, including patients with hepatocellular carcinoma (68.0% vs. 8.9% in the placebo group; P < .0001) and those without it (77.0% vs. 21.6%; P < .0001). Rates of treatment-emergent adverse events were similar between the lusutrombopag and placebo groups, and patients with hepatocellular carcinoma were not at increased risk for thrombosis, Naim Alkhouri, MD, of Texas Liver Institute in San Antonio, and associates wrote in Clinical Gastroenterology and Hepatology.

Platelet transfusion is the treatment mainstay for patients with thrombocytopenia related to cirrhosis who are undergoing invasive procedures, but its effects are short-lived, and at least one in five transfusions fails. Thrombopoietin agonists such as lusutrombopag are efficacious and approved in this setting, but they can be prothrombotic, particularly in patients with hepatocellular carcinoma, who already are at heightened risk for portal vein thrombosis.

Dr. Alkhouri and associates performed an integrated analysis of the PLUS 1 trial (Japan, October 2013–May 2014) and the L-PLUS 2 (global, June 2015–April 2017). Participants were adults with Child-Pugh Class A or B chronic liver disease and baseline platelet counts under 50 x 10⁹ per L who were scheduled for invasive procedures. Of the 270 patients, 95 had hepatocellular carcinoma. Patients were randomly assigned on a one-to-one basis to receive either lusutrombopag (3 mg) or placebo daily for up to 7 days before procedures. The primary endpoint was the percentage of patients in the per-protocol population who did not need a platelet transfusion before the invasive procedure or rescue therapy within 7 days afterward.

The treatment and placebo arms were similar except that patients with hepatocellular carcinoma were about 10 years older on average. In patients with hepatocellular carcinoma, 60.5% more lusutrombopag recipients than placebo recipients met the primary endpoint, and rates of bleeding-related adverse events were 9.1% and 15.7%, respectively. In patients with other chronic liver diseases, 52.6% more lusutrombopag recipients met the primary endpoint. Rates of bleeding-related adverse events were 5% and 10.6%.

“Approximately 88% of patients with hepatocellular carcinoma underwent a liver-related procedure, compared with approximately 10% of patients without hepatocellular carcinoma,” the investigators wrote. “This is significant because ablations or transcatheter arterial chemoembolizations can be associated with serious bleeding complications. It is clinically important that, given the greater number of liver-related procedures, the incidence of bleeding-related adverse events was lower in patients treated with lusutrombopag than placebo.”

Imaging after the procedures confirmed low rates of thromboses in both groups and subgroups. Four patients developed portal vein thromboses, including two lusutrombopag recipients (one of whom had hepatocellular carcinoma) and two placebo recipients without hepatocellular carcinoma.

These trials excluded patients undergoing major surgical procedures and those with decompensated cirrhosis; portal vein thrombosis; hematopoietic tumors; aplastic anemia; myelodysplastic syndrome; myelofibrosis; liver transplantation; splenectomy; and thrombocytopenia that was congenital, autoimmune, or drug induced. “A limitation of this study was the high rate of protocol violations related to platelet transfusions,” the researchers noted. “A number of patients [42 in all] were excluded from the per-protocol population owing to receipt of unnecessary platelet transfusions, or because they did not receive a needed platelet transfusion.”Shionogi makes lusutrombopag and sponsored the study. Dr. Alkhouri reported an advisory relationship with Shionogi and Dova Pharma. Two coinvestigators reported being employed by Shionogi. Three coinvestigators also disclosed ties to Shionogi and to several other pharmaceutical companies.

SOURCE: Alkhouri N et al. Clin Gastroenterol Hepatol. 2020 Mar 20. doi: 10.1016/j.cgh.2020.03.032.