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Light alcohol use did not affect liver fibrosis progression in HIV/HCV-coinfected women
Women coinfected with HIV and hepatitis C virus who drank light and moderate amounts of alcohol did not experience significant progression of liver fibrosis, compared with those who drank heavily, results from a large cohort study found.
“Although heavy alcohol use is clearly detrimental to the health of patients with CHC [chronic hepatitis C], it is unclear whether consumption of smaller quantities of alcohol impact fibrosis progression,” researchers led by Erin M. Kelly, MD, wrote in a study published online Aug. 16 in Clinical Infectious Diseases (doi: 10.1093/cid/cix716). “Many patients with CHC consume alcohol and are unable or unwilling to completely abstain. Some studies have suggested a linear dose-response relationship for fibrosis progression even at lower quantities, while others have not clearly demonstrated a risk for fibrosis progression below 20-50 g of alcohol per day. HIV/HCV [hepatitis C virus]-coinfected patients have accelerated fibrosis progression, compared with HCV monoinfected individuals. Whether regular consumption of small quantities of alcohol further increase the rate of fibrosis progression is unknown.”
At baseline, the mean age of study participants was 40 years, their mean body mass index was 26 kg/m2, 17% had diabetes, and 11% had significant fibrosis, defined as a FIB-4 index of greater than 3.25. Nearly half (46%) reported no alcohol use; 26.8% reported light use; 7.1%, moderate use; and 19.7%, heavy use. The median FIB-4 scores at entry were similar between groups. On multivariable analysis, no significant difference in fibrosis progression was observed in abstainers, compared with those who reported light and moderate alcohol use (0.004 and 0.006 FIB-4 units/year, respectively). On the other hand, those who reported very heavy drinking showed significant fibrosis acceleration, compared with abstainers (0.25 FIB-4 units/year), while those who reported drinking 8-14 drinks per week showed minimal acceleration of fibrosis progression (0.04 FIB-4 units/year).
“Of interest, despite WIHS research clinicians recommending limiting or avoiding alcohol at semiannual visits, most women who consumed alcohol at WIHS entry continued to have periods of alcohol use in follow-up,” Dr. Kelly and her associates wrote. “This suggests that, despite being enrolled in a long-term observational cohort study, patients did not change their drinking behaviors, limiting any potential bias in changing behaviors due to participation in a research study.”
The investigators acknowledged certain limitations of the study, including the fact that while current alcohol use was captured at study entry and at follow-up, lifetime alcohol exposure was not collected. “Women categorized as abstinent may have had a prior history of alcohol use,” they noted. “Some of these women may represent ‘sick abstainers’ that have ceased alcohol consumption due to the severity of their liver disease. This may explain the finding that entry fibrosis scores were similar between groups, when one would expect heavy users to have higher fibrosis scores, as compared to abstinent patients.”
The study was supported by the National Institute of Allergy and Infectious Diseases, with additional cofunding from the National Institute of Child Health and Human Development; the National Cancer Institute; the National Institute on Drug Abuse; the National Institute on Mental Health; and the University of California, San Francisco, Liver Center Biostatistics Core. The researchers reported having no financial disclosures.
This study highlights the importance of assessing alcohol consumption during routine practice (for example, with the Alcohol Use Disorders Identification Test) to classify patients’ level of use. HIV/HCV-coinfected women should be counseled to minimize alcohol consumption, and any patient with evidence of advanced hepatic fibrosis/cirrhosis should avoid alcohol use, given that the risk of liver complications, such as decompensated cirrhosis and hepatocellular carcinoma, associated with light or moderate use remains unknown in this group. However, some may be unable or unwilling to completely abstain from alcohol because of mental health or substance use disorders. This study suggests that light or moderate alcohol use by coinfected women is not associated with accelerated liver fibrosis progression, as measured by changes in the FIB-4 score.
Future studies should determine the effects of light and moderate alcohol consumption on changes in other noninvasive measures of liver fibrosis, such as transient elastography, and on rates of liver complications, such as hepatic decompensation and hepatocellular carcinoma, in HIV/HCV-coinfected men and women to confirm this study’s findings. Additional research also is needed to evaluate the effects of alcohol use categories on adherence to direct-acting antiviral therapy and HCV treatment response to examine whether these outcomes differ by HIV status and sex. These data will further help inform whether there is a “safe” level of alcohol intake in HIV/HCV patients.
This text is taken from a commentary published online Aug. 16 in Clinical Infectious Diseases (doi: 10.1093/cid/cix720). Vincent Lo Re III, MD, MSCE, is with the Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania, Philadelphia. He disclosed having received research grant support from the University of Pennsylvania, the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and AstraZeneca.
This study highlights the importance of assessing alcohol consumption during routine practice (for example, with the Alcohol Use Disorders Identification Test) to classify patients’ level of use. HIV/HCV-coinfected women should be counseled to minimize alcohol consumption, and any patient with evidence of advanced hepatic fibrosis/cirrhosis should avoid alcohol use, given that the risk of liver complications, such as decompensated cirrhosis and hepatocellular carcinoma, associated with light or moderate use remains unknown in this group. However, some may be unable or unwilling to completely abstain from alcohol because of mental health or substance use disorders. This study suggests that light or moderate alcohol use by coinfected women is not associated with accelerated liver fibrosis progression, as measured by changes in the FIB-4 score.
Future studies should determine the effects of light and moderate alcohol consumption on changes in other noninvasive measures of liver fibrosis, such as transient elastography, and on rates of liver complications, such as hepatic decompensation and hepatocellular carcinoma, in HIV/HCV-coinfected men and women to confirm this study’s findings. Additional research also is needed to evaluate the effects of alcohol use categories on adherence to direct-acting antiviral therapy and HCV treatment response to examine whether these outcomes differ by HIV status and sex. These data will further help inform whether there is a “safe” level of alcohol intake in HIV/HCV patients.
This text is taken from a commentary published online Aug. 16 in Clinical Infectious Diseases (doi: 10.1093/cid/cix720). Vincent Lo Re III, MD, MSCE, is with the Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania, Philadelphia. He disclosed having received research grant support from the University of Pennsylvania, the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and AstraZeneca.
This study highlights the importance of assessing alcohol consumption during routine practice (for example, with the Alcohol Use Disorders Identification Test) to classify patients’ level of use. HIV/HCV-coinfected women should be counseled to minimize alcohol consumption, and any patient with evidence of advanced hepatic fibrosis/cirrhosis should avoid alcohol use, given that the risk of liver complications, such as decompensated cirrhosis and hepatocellular carcinoma, associated with light or moderate use remains unknown in this group. However, some may be unable or unwilling to completely abstain from alcohol because of mental health or substance use disorders. This study suggests that light or moderate alcohol use by coinfected women is not associated with accelerated liver fibrosis progression, as measured by changes in the FIB-4 score.
Future studies should determine the effects of light and moderate alcohol consumption on changes in other noninvasive measures of liver fibrosis, such as transient elastography, and on rates of liver complications, such as hepatic decompensation and hepatocellular carcinoma, in HIV/HCV-coinfected men and women to confirm this study’s findings. Additional research also is needed to evaluate the effects of alcohol use categories on adherence to direct-acting antiviral therapy and HCV treatment response to examine whether these outcomes differ by HIV status and sex. These data will further help inform whether there is a “safe” level of alcohol intake in HIV/HCV patients.
This text is taken from a commentary published online Aug. 16 in Clinical Infectious Diseases (doi: 10.1093/cid/cix720). Vincent Lo Re III, MD, MSCE, is with the Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania, Philadelphia. He disclosed having received research grant support from the University of Pennsylvania, the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and AstraZeneca.
Women coinfected with HIV and hepatitis C virus who drank light and moderate amounts of alcohol did not experience significant progression of liver fibrosis, compared with those who drank heavily, results from a large cohort study found.
“Although heavy alcohol use is clearly detrimental to the health of patients with CHC [chronic hepatitis C], it is unclear whether consumption of smaller quantities of alcohol impact fibrosis progression,” researchers led by Erin M. Kelly, MD, wrote in a study published online Aug. 16 in Clinical Infectious Diseases (doi: 10.1093/cid/cix716). “Many patients with CHC consume alcohol and are unable or unwilling to completely abstain. Some studies have suggested a linear dose-response relationship for fibrosis progression even at lower quantities, while others have not clearly demonstrated a risk for fibrosis progression below 20-50 g of alcohol per day. HIV/HCV [hepatitis C virus]-coinfected patients have accelerated fibrosis progression, compared with HCV monoinfected individuals. Whether regular consumption of small quantities of alcohol further increase the rate of fibrosis progression is unknown.”
At baseline, the mean age of study participants was 40 years, their mean body mass index was 26 kg/m2, 17% had diabetes, and 11% had significant fibrosis, defined as a FIB-4 index of greater than 3.25. Nearly half (46%) reported no alcohol use; 26.8% reported light use; 7.1%, moderate use; and 19.7%, heavy use. The median FIB-4 scores at entry were similar between groups. On multivariable analysis, no significant difference in fibrosis progression was observed in abstainers, compared with those who reported light and moderate alcohol use (0.004 and 0.006 FIB-4 units/year, respectively). On the other hand, those who reported very heavy drinking showed significant fibrosis acceleration, compared with abstainers (0.25 FIB-4 units/year), while those who reported drinking 8-14 drinks per week showed minimal acceleration of fibrosis progression (0.04 FIB-4 units/year).
“Of interest, despite WIHS research clinicians recommending limiting or avoiding alcohol at semiannual visits, most women who consumed alcohol at WIHS entry continued to have periods of alcohol use in follow-up,” Dr. Kelly and her associates wrote. “This suggests that, despite being enrolled in a long-term observational cohort study, patients did not change their drinking behaviors, limiting any potential bias in changing behaviors due to participation in a research study.”
The investigators acknowledged certain limitations of the study, including the fact that while current alcohol use was captured at study entry and at follow-up, lifetime alcohol exposure was not collected. “Women categorized as abstinent may have had a prior history of alcohol use,” they noted. “Some of these women may represent ‘sick abstainers’ that have ceased alcohol consumption due to the severity of their liver disease. This may explain the finding that entry fibrosis scores were similar between groups, when one would expect heavy users to have higher fibrosis scores, as compared to abstinent patients.”
The study was supported by the National Institute of Allergy and Infectious Diseases, with additional cofunding from the National Institute of Child Health and Human Development; the National Cancer Institute; the National Institute on Drug Abuse; the National Institute on Mental Health; and the University of California, San Francisco, Liver Center Biostatistics Core. The researchers reported having no financial disclosures.
Women coinfected with HIV and hepatitis C virus who drank light and moderate amounts of alcohol did not experience significant progression of liver fibrosis, compared with those who drank heavily, results from a large cohort study found.
“Although heavy alcohol use is clearly detrimental to the health of patients with CHC [chronic hepatitis C], it is unclear whether consumption of smaller quantities of alcohol impact fibrosis progression,” researchers led by Erin M. Kelly, MD, wrote in a study published online Aug. 16 in Clinical Infectious Diseases (doi: 10.1093/cid/cix716). “Many patients with CHC consume alcohol and are unable or unwilling to completely abstain. Some studies have suggested a linear dose-response relationship for fibrosis progression even at lower quantities, while others have not clearly demonstrated a risk for fibrosis progression below 20-50 g of alcohol per day. HIV/HCV [hepatitis C virus]-coinfected patients have accelerated fibrosis progression, compared with HCV monoinfected individuals. Whether regular consumption of small quantities of alcohol further increase the rate of fibrosis progression is unknown.”
At baseline, the mean age of study participants was 40 years, their mean body mass index was 26 kg/m2, 17% had diabetes, and 11% had significant fibrosis, defined as a FIB-4 index of greater than 3.25. Nearly half (46%) reported no alcohol use; 26.8% reported light use; 7.1%, moderate use; and 19.7%, heavy use. The median FIB-4 scores at entry were similar between groups. On multivariable analysis, no significant difference in fibrosis progression was observed in abstainers, compared with those who reported light and moderate alcohol use (0.004 and 0.006 FIB-4 units/year, respectively). On the other hand, those who reported very heavy drinking showed significant fibrosis acceleration, compared with abstainers (0.25 FIB-4 units/year), while those who reported drinking 8-14 drinks per week showed minimal acceleration of fibrosis progression (0.04 FIB-4 units/year).
“Of interest, despite WIHS research clinicians recommending limiting or avoiding alcohol at semiannual visits, most women who consumed alcohol at WIHS entry continued to have periods of alcohol use in follow-up,” Dr. Kelly and her associates wrote. “This suggests that, despite being enrolled in a long-term observational cohort study, patients did not change their drinking behaviors, limiting any potential bias in changing behaviors due to participation in a research study.”
The investigators acknowledged certain limitations of the study, including the fact that while current alcohol use was captured at study entry and at follow-up, lifetime alcohol exposure was not collected. “Women categorized as abstinent may have had a prior history of alcohol use,” they noted. “Some of these women may represent ‘sick abstainers’ that have ceased alcohol consumption due to the severity of their liver disease. This may explain the finding that entry fibrosis scores were similar between groups, when one would expect heavy users to have higher fibrosis scores, as compared to abstinent patients.”
The study was supported by the National Institute of Allergy and Infectious Diseases, with additional cofunding from the National Institute of Child Health and Human Development; the National Cancer Institute; the National Institute on Drug Abuse; the National Institute on Mental Health; and the University of California, San Francisco, Liver Center Biostatistics Core. The researchers reported having no financial disclosures.
FROM CLINICAL INFECTIOUS DISEASES
Key clinical point:
Major finding: On multivariable analysis, no significant difference in fibrosis progression was observed in abstainers, compared with those who reported light and moderate alcohol use (0.004 and 0.006 FIB-4 units/year, respectively).
Data source: A cohort study of 686 participants in the multicenter Women’s Interagency HIV Study.
Disclosures: The study was supported by the National Institute of Allergy and Infectious Diseases, with additional cofunding from the National Institute of Child Health and Human Development, the National Cancer Institute, the National Institute on Drug Abuse, the National Institute on Mental Health, and the UCSF Liver Center Biostatistics Core. The researchers reported having no financial disclosures.
Hot topics in 2017
The 2017 Postgraduate Course started out with four hot topics that dominated the year – opioid dependence, a cure for hepatitis C, and understanding and then manipulating the microbiome. From David Dickerson, MD, we learned that abdominal pain is complex and with an evolving classification scheme. Ignoring the biopsychosocial aspects and origins of pain is a sure way to lead to addiction and “pain behavior.” He reviewed the opioid guidelines that involve a comprehensive approach to therapy – setting functional goals, assessing the risks and benefits, and using the lowest necessary doses of short-acting agents for a defined period of time and then reassessing. In patients with chronic pain and opioid dependence, the gastroenterologist should seek the help of a chronic pain specialist. We should also refer for nonpharmacologic therapy such as cognitive behavioral therapy and biofeedback.
Norah Terrault, MD, MPH, discussed management of chronic hepatitis C (HCV) after the cure, achievable in more than 95% of patients, which has resulted in a sharp decline in listings for liver transplant. A cure is defined as undetectable HCV RNA 12 weeks after completion of therapy. So what happens next? If the patient is at risk for reinfection, they should have HCV RNA testing annually or if their liver enzymes increase. Otherwise, if their pretreatment fibrosis is low stage, no further monitoring is needed and they can follow up with their primary care provider. Intermediate-stage fibrosis should be monitored for progression. Advanced-stage fibrosis needs long-term follow-up for hepatocellular carcinoma and variceal surveillance. Modifiable risk factors, i.e., metabolic fatty liver and alcohol abuse, should be identified with appropriate counseling provided.
We went back to the microbiome for our last talk: Larry Brandt, MD, AGAF, discussed FMT for Clostridium difficile infection (CDI). Patients should be considered for FMT if they have more than 3 recurrences of mild to moderate CDI and failure to respond to standard therapy; more than 2 episodes of CDI resulting in hospitalization and significant morbidity; moderate CDI with no response after 1 week of standard therapy; and severe CDI with no response to standard therapy within 48 hours. Serious adverse events associated with FMT include infections and perhaps new-onset immune-mediated disease such as Sjogren’s, rheumatoid arthritis, and idiopathic thrombocytopenic purpura. It is hoped that the NIH-sponsored AGA national registry for FMT will help better define outcomes and adverse events over the next 10 years.
Dr. Mahadevan is professor of clinical medicine at UCSF Medical Center, San Francisco. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017.
The 2017 Postgraduate Course started out with four hot topics that dominated the year – opioid dependence, a cure for hepatitis C, and understanding and then manipulating the microbiome. From David Dickerson, MD, we learned that abdominal pain is complex and with an evolving classification scheme. Ignoring the biopsychosocial aspects and origins of pain is a sure way to lead to addiction and “pain behavior.” He reviewed the opioid guidelines that involve a comprehensive approach to therapy – setting functional goals, assessing the risks and benefits, and using the lowest necessary doses of short-acting agents for a defined period of time and then reassessing. In patients with chronic pain and opioid dependence, the gastroenterologist should seek the help of a chronic pain specialist. We should also refer for nonpharmacologic therapy such as cognitive behavioral therapy and biofeedback.
Norah Terrault, MD, MPH, discussed management of chronic hepatitis C (HCV) after the cure, achievable in more than 95% of patients, which has resulted in a sharp decline in listings for liver transplant. A cure is defined as undetectable HCV RNA 12 weeks after completion of therapy. So what happens next? If the patient is at risk for reinfection, they should have HCV RNA testing annually or if their liver enzymes increase. Otherwise, if their pretreatment fibrosis is low stage, no further monitoring is needed and they can follow up with their primary care provider. Intermediate-stage fibrosis should be monitored for progression. Advanced-stage fibrosis needs long-term follow-up for hepatocellular carcinoma and variceal surveillance. Modifiable risk factors, i.e., metabolic fatty liver and alcohol abuse, should be identified with appropriate counseling provided.
We went back to the microbiome for our last talk: Larry Brandt, MD, AGAF, discussed FMT for Clostridium difficile infection (CDI). Patients should be considered for FMT if they have more than 3 recurrences of mild to moderate CDI and failure to respond to standard therapy; more than 2 episodes of CDI resulting in hospitalization and significant morbidity; moderate CDI with no response after 1 week of standard therapy; and severe CDI with no response to standard therapy within 48 hours. Serious adverse events associated with FMT include infections and perhaps new-onset immune-mediated disease such as Sjogren’s, rheumatoid arthritis, and idiopathic thrombocytopenic purpura. It is hoped that the NIH-sponsored AGA national registry for FMT will help better define outcomes and adverse events over the next 10 years.
Dr. Mahadevan is professor of clinical medicine at UCSF Medical Center, San Francisco. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017.
The 2017 Postgraduate Course started out with four hot topics that dominated the year – opioid dependence, a cure for hepatitis C, and understanding and then manipulating the microbiome. From David Dickerson, MD, we learned that abdominal pain is complex and with an evolving classification scheme. Ignoring the biopsychosocial aspects and origins of pain is a sure way to lead to addiction and “pain behavior.” He reviewed the opioid guidelines that involve a comprehensive approach to therapy – setting functional goals, assessing the risks and benefits, and using the lowest necessary doses of short-acting agents for a defined period of time and then reassessing. In patients with chronic pain and opioid dependence, the gastroenterologist should seek the help of a chronic pain specialist. We should also refer for nonpharmacologic therapy such as cognitive behavioral therapy and biofeedback.
Norah Terrault, MD, MPH, discussed management of chronic hepatitis C (HCV) after the cure, achievable in more than 95% of patients, which has resulted in a sharp decline in listings for liver transplant. A cure is defined as undetectable HCV RNA 12 weeks after completion of therapy. So what happens next? If the patient is at risk for reinfection, they should have HCV RNA testing annually or if their liver enzymes increase. Otherwise, if their pretreatment fibrosis is low stage, no further monitoring is needed and they can follow up with their primary care provider. Intermediate-stage fibrosis should be monitored for progression. Advanced-stage fibrosis needs long-term follow-up for hepatocellular carcinoma and variceal surveillance. Modifiable risk factors, i.e., metabolic fatty liver and alcohol abuse, should be identified with appropriate counseling provided.
We went back to the microbiome for our last talk: Larry Brandt, MD, AGAF, discussed FMT for Clostridium difficile infection (CDI). Patients should be considered for FMT if they have more than 3 recurrences of mild to moderate CDI and failure to respond to standard therapy; more than 2 episodes of CDI resulting in hospitalization and significant morbidity; moderate CDI with no response after 1 week of standard therapy; and severe CDI with no response to standard therapy within 48 hours. Serious adverse events associated with FMT include infections and perhaps new-onset immune-mediated disease such as Sjogren’s, rheumatoid arthritis, and idiopathic thrombocytopenic purpura. It is hoped that the NIH-sponsored AGA national registry for FMT will help better define outcomes and adverse events over the next 10 years.
Dr. Mahadevan is professor of clinical medicine at UCSF Medical Center, San Francisco. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017.
NASH did not increase risk of poor liver transplantation outcomes
Adults with nonalcoholic steatohepatitis (NASH) fared as well on key outcome measures as other liver transplant recipients, despite having significantly more comorbidities, according to the results of a single-center retrospective cohort study.
Major morbidity, mortality, and rates of graft survival after 90 days were similar between patients who underwent transplantation for NASH and those who underwent it for another cirrhotic liver condition, wrote Eline H. van den Berg, MD, of University Medical Center Groningen (the Netherlands) with her associates. “These results are comforting, considering the expected increase of patients with NASH cirrhosis in the near future,” the researchers concluded. “Future analysis regarding the recurrence of nonalcoholic fatty liver disease, development of long-term complications, long-term graft patency, and occurrence of comorbid diseases after LT [liver transplantation] is mandatory to better understand the natural history and risk profile of NASH patients and to prevent and treat its complications.” The findings were published online in Digestive and Liver Disease (Dig Liver Dis. 2017 Aug 11. doi: 10.1016/j.dld.2017.08.022).
Nonalcoholic fatty liver disease begins as steatosis and can progress to NASH, fibrosis, and cirrhosis. The global obesity epidemic is amplifying its incidence, and about 26% of patients who develop NASH ultimately develop cirrhosis. Cirrhosis itself increases the risk of in-hospital death or prolonged length of postoperative stay, but patients with NASH also have obesity and cardiovascular disease, which might “tremendously increase” the risk of poor postoperative outcomes, the researchers said. Because prior research had focused mainly on mortality and had reported conflicting results, they used the Clavien-Dindo classification system to retrospectively study rates of complications among 169 adults who underwent liver transplantation at their center from 2009 through 2015, including 34 (20%) patients with NASH cirrhosis.
Patients with NASH were significantly older than other transplant recipients (59 versus 55 years, P = .01) and had markedly higher rates of obesity (62% versus 8%; P less than .01), diabetes mellitus (74% versus 20%; P less than .01), metabolic syndrome (83% versus 38%; P less than .01), hypertension (61% versus 30%; P less than .01), and cardiovascular disease (29% versus 11%; P less than .01). Despite these differences, the groups had statistically similar rates of postoperative mortality (3% in both groups), 90-day graft survival posttransplantation (94% and 90%, respectively), and major postoperative complications, including biopsy-proven acute cellular rejection (3% and 7%), hepatic artery thrombosis (0% and 7%), relaparotomy (15% and 24%), primary nonfunction (0% and 1.6%), retransplantation (6% and 7%), sepsis (12% and 13%), gastrointestinal infection (24% and 36%), fever of unknown origin (18% and 14%), and renal replacement therapy (15% and 24%).
After accounting for age, sex, transplant year, and donor characteristics, NASH patients were at significantly increased risk of grade 2 urogenital infections, compared with other patients (odds ratio, 3.4; 95% confidence interval, 1.1 to 10.6; P = .03). Grade 1 complications also were more common with NASH than otherwise (77% versus 59%), and the difference remained statistically significant in the multivariable analysis (OR, 1.6; 95% CI, 1.03 to 2.63; P = .04).
The study used a strict, internationally accepted definition of NASH – all patients either had cases confirmed by biopsy, had metabolic syndrome, or had obesity and type 2 diabetes mellitus, and, further, none had hepatitis or alcoholic liver disease. None of the patients in the study received transplants for acute liver failure or noncirrhotic liver disease, and none were 70 years or older, which is the cutoff age for liver transplantation in the Netherlands.
The investigators received no funding for the study and reported having no conflicts of interest.
Adults with nonalcoholic steatohepatitis (NASH) fared as well on key outcome measures as other liver transplant recipients, despite having significantly more comorbidities, according to the results of a single-center retrospective cohort study.
Major morbidity, mortality, and rates of graft survival after 90 days were similar between patients who underwent transplantation for NASH and those who underwent it for another cirrhotic liver condition, wrote Eline H. van den Berg, MD, of University Medical Center Groningen (the Netherlands) with her associates. “These results are comforting, considering the expected increase of patients with NASH cirrhosis in the near future,” the researchers concluded. “Future analysis regarding the recurrence of nonalcoholic fatty liver disease, development of long-term complications, long-term graft patency, and occurrence of comorbid diseases after LT [liver transplantation] is mandatory to better understand the natural history and risk profile of NASH patients and to prevent and treat its complications.” The findings were published online in Digestive and Liver Disease (Dig Liver Dis. 2017 Aug 11. doi: 10.1016/j.dld.2017.08.022).
Nonalcoholic fatty liver disease begins as steatosis and can progress to NASH, fibrosis, and cirrhosis. The global obesity epidemic is amplifying its incidence, and about 26% of patients who develop NASH ultimately develop cirrhosis. Cirrhosis itself increases the risk of in-hospital death or prolonged length of postoperative stay, but patients with NASH also have obesity and cardiovascular disease, which might “tremendously increase” the risk of poor postoperative outcomes, the researchers said. Because prior research had focused mainly on mortality and had reported conflicting results, they used the Clavien-Dindo classification system to retrospectively study rates of complications among 169 adults who underwent liver transplantation at their center from 2009 through 2015, including 34 (20%) patients with NASH cirrhosis.
Patients with NASH were significantly older than other transplant recipients (59 versus 55 years, P = .01) and had markedly higher rates of obesity (62% versus 8%; P less than .01), diabetes mellitus (74% versus 20%; P less than .01), metabolic syndrome (83% versus 38%; P less than .01), hypertension (61% versus 30%; P less than .01), and cardiovascular disease (29% versus 11%; P less than .01). Despite these differences, the groups had statistically similar rates of postoperative mortality (3% in both groups), 90-day graft survival posttransplantation (94% and 90%, respectively), and major postoperative complications, including biopsy-proven acute cellular rejection (3% and 7%), hepatic artery thrombosis (0% and 7%), relaparotomy (15% and 24%), primary nonfunction (0% and 1.6%), retransplantation (6% and 7%), sepsis (12% and 13%), gastrointestinal infection (24% and 36%), fever of unknown origin (18% and 14%), and renal replacement therapy (15% and 24%).
After accounting for age, sex, transplant year, and donor characteristics, NASH patients were at significantly increased risk of grade 2 urogenital infections, compared with other patients (odds ratio, 3.4; 95% confidence interval, 1.1 to 10.6; P = .03). Grade 1 complications also were more common with NASH than otherwise (77% versus 59%), and the difference remained statistically significant in the multivariable analysis (OR, 1.6; 95% CI, 1.03 to 2.63; P = .04).
The study used a strict, internationally accepted definition of NASH – all patients either had cases confirmed by biopsy, had metabolic syndrome, or had obesity and type 2 diabetes mellitus, and, further, none had hepatitis or alcoholic liver disease. None of the patients in the study received transplants for acute liver failure or noncirrhotic liver disease, and none were 70 years or older, which is the cutoff age for liver transplantation in the Netherlands.
The investigators received no funding for the study and reported having no conflicts of interest.
Adults with nonalcoholic steatohepatitis (NASH) fared as well on key outcome measures as other liver transplant recipients, despite having significantly more comorbidities, according to the results of a single-center retrospective cohort study.
Major morbidity, mortality, and rates of graft survival after 90 days were similar between patients who underwent transplantation for NASH and those who underwent it for another cirrhotic liver condition, wrote Eline H. van den Berg, MD, of University Medical Center Groningen (the Netherlands) with her associates. “These results are comforting, considering the expected increase of patients with NASH cirrhosis in the near future,” the researchers concluded. “Future analysis regarding the recurrence of nonalcoholic fatty liver disease, development of long-term complications, long-term graft patency, and occurrence of comorbid diseases after LT [liver transplantation] is mandatory to better understand the natural history and risk profile of NASH patients and to prevent and treat its complications.” The findings were published online in Digestive and Liver Disease (Dig Liver Dis. 2017 Aug 11. doi: 10.1016/j.dld.2017.08.022).
Nonalcoholic fatty liver disease begins as steatosis and can progress to NASH, fibrosis, and cirrhosis. The global obesity epidemic is amplifying its incidence, and about 26% of patients who develop NASH ultimately develop cirrhosis. Cirrhosis itself increases the risk of in-hospital death or prolonged length of postoperative stay, but patients with NASH also have obesity and cardiovascular disease, which might “tremendously increase” the risk of poor postoperative outcomes, the researchers said. Because prior research had focused mainly on mortality and had reported conflicting results, they used the Clavien-Dindo classification system to retrospectively study rates of complications among 169 adults who underwent liver transplantation at their center from 2009 through 2015, including 34 (20%) patients with NASH cirrhosis.
Patients with NASH were significantly older than other transplant recipients (59 versus 55 years, P = .01) and had markedly higher rates of obesity (62% versus 8%; P less than .01), diabetes mellitus (74% versus 20%; P less than .01), metabolic syndrome (83% versus 38%; P less than .01), hypertension (61% versus 30%; P less than .01), and cardiovascular disease (29% versus 11%; P less than .01). Despite these differences, the groups had statistically similar rates of postoperative mortality (3% in both groups), 90-day graft survival posttransplantation (94% and 90%, respectively), and major postoperative complications, including biopsy-proven acute cellular rejection (3% and 7%), hepatic artery thrombosis (0% and 7%), relaparotomy (15% and 24%), primary nonfunction (0% and 1.6%), retransplantation (6% and 7%), sepsis (12% and 13%), gastrointestinal infection (24% and 36%), fever of unknown origin (18% and 14%), and renal replacement therapy (15% and 24%).
After accounting for age, sex, transplant year, and donor characteristics, NASH patients were at significantly increased risk of grade 2 urogenital infections, compared with other patients (odds ratio, 3.4; 95% confidence interval, 1.1 to 10.6; P = .03). Grade 1 complications also were more common with NASH than otherwise (77% versus 59%), and the difference remained statistically significant in the multivariable analysis (OR, 1.6; 95% CI, 1.03 to 2.63; P = .04).
The study used a strict, internationally accepted definition of NASH – all patients either had cases confirmed by biopsy, had metabolic syndrome, or had obesity and type 2 diabetes mellitus, and, further, none had hepatitis or alcoholic liver disease. None of the patients in the study received transplants for acute liver failure or noncirrhotic liver disease, and none were 70 years or older, which is the cutoff age for liver transplantation in the Netherlands.
The investigators received no funding for the study and reported having no conflicts of interest.
FROM DIGESTIVE AND LIVER DISEASES
Key clinical point: Adults with nonalcoholic steatohepatitis (NASH) fared as well as on key outcome measures as other liver transplant recipients, despite having significantly more comorbidities.
Major finding: Patients with and without NASH had statistically similar rates of postoperative mortality (3% in both groups), 90-day graft survival (94% and 90%, respectively), and major postoperative complications.
Data source: A single-center retrospective cohort study of 169 adult liver transplant recipients, of whom 20% were transplanted for NASH cirrhosis.
Disclosures: The investigators received no funding for the study and reported having no conflicts of interest.
FDA approves faster, pangenotypic cure for hep C virus
The first pangenotypic treatment for the hepatitis C virus, which also shaves 4 weeks off current regimens, has just been approved by the Food and Drug Administration.
Manufactured by AbbVie, glecaprevir/pibrentasvir (Mavyret) combines a nonstructural protein 3/4A protease inhibitor with a next-generation NS5A protein inhibitor for a once-daily, ribavirin-free treatment for adults with any of the major genotypes of chronic hepatitis C virus (HCV) infection.
“This approval provides a shorter treatment duration for many patients, and also a treatment option for certain patients with genotype 1 infection, the most common HCV genotype in the United States, who were not successfully treated with other direct-acting antiviral treatments in the past,” Edward Cox, MD, director of the office of antimicrobial products in the FDA’s Center for Drug Evaluation and Research, Silver Spring, Md., said in a statement.
The 8-week regimen is indicated in patients without cirrhosis or with compensated cirrhosis, who are new to treatment, and those with limited treatment options, such as patients with chronic kidney disease, including those on dialysis. The intervention also is indicated in adults with HCV genotype 1 who have been treated with either of the drugs in the combination, but not both. Glecaprevir/pibrentasvir is not recommended in patients with moderate cirrhosis and is contraindicated in patients with severe cirrhosis and in those taking the drugs atazanavir and rifampin.
The safety and efficacy of the treatment were evaluated in approximately 2,300 adults with genotype 1, 2, 3, 4, 5 or 6 HCV infection without cirrhosis or with mild cirrhosis. In the clinical trials, between 92% and 100% of patients treated with glecaprevir/pibrentasvir for 8, 12, or 16 weeks had no detectable serum levels of the virus 12 weeks after finishing treatment. The most commonly reported adverse reactions were headache, fatigue, and nausea.
The FDA directs health care professionals to test all patients for current or prior hepatitis B virus (HBV) infection prior to starting this direct-acting antiviral drug combination since HBV reactivation has been reported in adult patients coinfected with both viruses who were undergoing or had completed treatment with HCV direct-acting antivirals and who were not receiving HBV antiviral therapy.
The AGA HCV Clinical Service Line provides tools to help you become more efficient, understand quality standards and improve the process of care for patients. Learn more at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c
The first pangenotypic treatment for the hepatitis C virus, which also shaves 4 weeks off current regimens, has just been approved by the Food and Drug Administration.
Manufactured by AbbVie, glecaprevir/pibrentasvir (Mavyret) combines a nonstructural protein 3/4A protease inhibitor with a next-generation NS5A protein inhibitor for a once-daily, ribavirin-free treatment for adults with any of the major genotypes of chronic hepatitis C virus (HCV) infection.
“This approval provides a shorter treatment duration for many patients, and also a treatment option for certain patients with genotype 1 infection, the most common HCV genotype in the United States, who were not successfully treated with other direct-acting antiviral treatments in the past,” Edward Cox, MD, director of the office of antimicrobial products in the FDA’s Center for Drug Evaluation and Research, Silver Spring, Md., said in a statement.
The 8-week regimen is indicated in patients without cirrhosis or with compensated cirrhosis, who are new to treatment, and those with limited treatment options, such as patients with chronic kidney disease, including those on dialysis. The intervention also is indicated in adults with HCV genotype 1 who have been treated with either of the drugs in the combination, but not both. Glecaprevir/pibrentasvir is not recommended in patients with moderate cirrhosis and is contraindicated in patients with severe cirrhosis and in those taking the drugs atazanavir and rifampin.
The safety and efficacy of the treatment were evaluated in approximately 2,300 adults with genotype 1, 2, 3, 4, 5 or 6 HCV infection without cirrhosis or with mild cirrhosis. In the clinical trials, between 92% and 100% of patients treated with glecaprevir/pibrentasvir for 8, 12, or 16 weeks had no detectable serum levels of the virus 12 weeks after finishing treatment. The most commonly reported adverse reactions were headache, fatigue, and nausea.
The FDA directs health care professionals to test all patients for current or prior hepatitis B virus (HBV) infection prior to starting this direct-acting antiviral drug combination since HBV reactivation has been reported in adult patients coinfected with both viruses who were undergoing or had completed treatment with HCV direct-acting antivirals and who were not receiving HBV antiviral therapy.
The AGA HCV Clinical Service Line provides tools to help you become more efficient, understand quality standards and improve the process of care for patients. Learn more at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c
The first pangenotypic treatment for the hepatitis C virus, which also shaves 4 weeks off current regimens, has just been approved by the Food and Drug Administration.
Manufactured by AbbVie, glecaprevir/pibrentasvir (Mavyret) combines a nonstructural protein 3/4A protease inhibitor with a next-generation NS5A protein inhibitor for a once-daily, ribavirin-free treatment for adults with any of the major genotypes of chronic hepatitis C virus (HCV) infection.
“This approval provides a shorter treatment duration for many patients, and also a treatment option for certain patients with genotype 1 infection, the most common HCV genotype in the United States, who were not successfully treated with other direct-acting antiviral treatments in the past,” Edward Cox, MD, director of the office of antimicrobial products in the FDA’s Center for Drug Evaluation and Research, Silver Spring, Md., said in a statement.
The 8-week regimen is indicated in patients without cirrhosis or with compensated cirrhosis, who are new to treatment, and those with limited treatment options, such as patients with chronic kidney disease, including those on dialysis. The intervention also is indicated in adults with HCV genotype 1 who have been treated with either of the drugs in the combination, but not both. Glecaprevir/pibrentasvir is not recommended in patients with moderate cirrhosis and is contraindicated in patients with severe cirrhosis and in those taking the drugs atazanavir and rifampin.
The safety and efficacy of the treatment were evaluated in approximately 2,300 adults with genotype 1, 2, 3, 4, 5 or 6 HCV infection without cirrhosis or with mild cirrhosis. In the clinical trials, between 92% and 100% of patients treated with glecaprevir/pibrentasvir for 8, 12, or 16 weeks had no detectable serum levels of the virus 12 weeks after finishing treatment. The most commonly reported adverse reactions were headache, fatigue, and nausea.
The FDA directs health care professionals to test all patients for current or prior hepatitis B virus (HBV) infection prior to starting this direct-acting antiviral drug combination since HBV reactivation has been reported in adult patients coinfected with both viruses who were undergoing or had completed treatment with HCV direct-acting antivirals and who were not receiving HBV antiviral therapy.
The AGA HCV Clinical Service Line provides tools to help you become more efficient, understand quality standards and improve the process of care for patients. Learn more at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c
Flashback to 2014
The development of therapies for chronic hepatitis C viral (HCV) infection has been a highlight of progress in hepatology and infectious disease over the last 25 years. From initial empiric approaches with interferon and ribavirin, to targeted and custom designed direct-acting antivirals (DAAs), there has been rapid improvement in efficacy and side effect profiles. Since we are dealing with a viral infection, loss of viremia after stopping therapy (sustained viral response, SVR) has been the marker of therapeutic success. SVR, however, is still a surrogate for clinical outcome and the analysis of 5-year follow-up in the December 2014 issue reported that in patients with SVR there was a reduction in risk of death, hepatocellular carcinoma, and liver transplantation. 
Observational studies have the potential for significant biases as decisions to treat are frequently based on the likelihood of a successful outcome. A randomized clinical trial for DAAs compared to control would of course be unethical at this stage. The scale of use of DAAs should allow a clear answer to this question within the next 2 years.
The development of therapies for chronic hepatitis C viral (HCV) infection has been a highlight of progress in hepatology and infectious disease over the last 25 years. From initial empiric approaches with interferon and ribavirin, to targeted and custom designed direct-acting antivirals (DAAs), there has been rapid improvement in efficacy and side effect profiles. Since we are dealing with a viral infection, loss of viremia after stopping therapy (sustained viral response, SVR) has been the marker of therapeutic success. SVR, however, is still a surrogate for clinical outcome and the analysis of 5-year follow-up in the December 2014 issue reported that in patients with SVR there was a reduction in risk of death, hepatocellular carcinoma, and liver transplantation.
Observational studies have the potential for significant biases as decisions to treat are frequently based on the likelihood of a successful outcome. A randomized clinical trial for DAAs compared to control would of course be unethical at this stage. The scale of use of DAAs should allow a clear answer to this question within the next 2 years.
The development of therapies for chronic hepatitis C viral (HCV) infection has been a highlight of progress in hepatology and infectious disease over the last 25 years. From initial empiric approaches with interferon and ribavirin, to targeted and custom designed direct-acting antivirals (DAAs), there has been rapid improvement in efficacy and side effect profiles. Since we are dealing with a viral infection, loss of viremia after stopping therapy (sustained viral response, SVR) has been the marker of therapeutic success. SVR, however, is still a surrogate for clinical outcome and the analysis of 5-year follow-up in the December 2014 issue reported that in patients with SVR there was a reduction in risk of death, hepatocellular carcinoma, and liver transplantation.
Observational studies have the potential for significant biases as decisions to treat are frequently based on the likelihood of a successful outcome. A randomized clinical trial for DAAs compared to control would of course be unethical at this stage. The scale of use of DAAs should allow a clear answer to this question within the next 2 years.
FDA advisory panel backs safety of new hepatitis B vaccine for adults
The Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee approved licensure for Heplisav-B, a new two-dose recombinant hepatitis B vaccination, after voting that presented data proved the vaccine to be safe for adults 18 and over.
At an advisory meeting, after hearing testimony from government researchers and representatives of Dynavax Technologies Corporation, the manufacturer of Heplisav-B, 11 members voted to approve the drug, 1 member voted no, and 3 abstained.
There are more than 20,000 new infections each year, with a reported increase of 21% between 2014 and 2015, according to research presented by William Schaffner, MD, professor of preventative medicine and infectious diseases at Vanderbilt University, Nashville, Tenn.
There are two approved immunizations for hepatitis B: Engerix-B, manufactured by GlaxoSmithKline, and Recombivax HB, by Merck. Both are three-dose, recombinant vaccines produced from yeast cells.
Like the current vaccines, Heplisav-B is a recombinant hepatitis B surface antigen that is derived from yeast; however, this vaccine would be administered in two doses over 1 month, as opposed to three doses over 6 months as is the schedule for currently approved vaccines. Both manufacturing representatives and approving members of the committee stressed this as an important factor due to vaccination dropout rates.
“We have a problem with hepatitis B infections in this country as well as problems with the current vaccines,“ said John Ward, MD, director of the division of viral hepatitis at the Centers for Disease Control and Prevention, “and they happen in these populations where, in terms of data, both of those audiences have problems about going for the second and third dose.”
Patients that drop out before the third dose are at high risk of infection, as only 20%-50% of adults have the appropriate seroprotection after two doses. However, only 54% of patients in a vaccine safety Datalink study reported completing the vaccination series, with 81% reporting having received two doses, according to Dr. Schaffner.
While the committee did approve the safety research as sufficient to approve use of Heplisav-B in adults 18 years and older, members of the committee had an issue with the drug’s correlation with myocardial infarction.
In one of the studies presented, Heplisav-B’s acute myocardial infarction (AMI) events (14 patients) greatly outnumbered those of Engerix-B (1 patient), presenting an AMI relative risk of 6.97.
Dynavax representatives, in response to this concern, presented intention to conduct a postmarketing analysis of the risk of MI in patients who have been administered Heplisav-B, which committee members considered to be a crucial contingency for approval.
“I would like to say I am for the approval of this vaccine, I just think as a statistician that the safety was inconclusive,” said Mei-Ling Ting Lee, PhD, director of the Biostatistics and Risk Assessment Center at the University of Maryland. “But I think for the pharmacological vigilance plan, I think that it will be good to have specific analysis for the myocardial infarction and other risks.”
Dynavax intends to introduce the vaccine commercially in the United States by the middle of 2018, according to a press release.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
The Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee approved licensure for Heplisav-B, a new two-dose recombinant hepatitis B vaccination, after voting that presented data proved the vaccine to be safe for adults 18 and over.
At an advisory meeting, after hearing testimony from government researchers and representatives of Dynavax Technologies Corporation, the manufacturer of Heplisav-B, 11 members voted to approve the drug, 1 member voted no, and 3 abstained.
There are more than 20,000 new infections each year, with a reported increase of 21% between 2014 and 2015, according to research presented by William Schaffner, MD, professor of preventative medicine and infectious diseases at Vanderbilt University, Nashville, Tenn.
There are two approved immunizations for hepatitis B: Engerix-B, manufactured by GlaxoSmithKline, and Recombivax HB, by Merck. Both are three-dose, recombinant vaccines produced from yeast cells.
Like the current vaccines, Heplisav-B is a recombinant hepatitis B surface antigen that is derived from yeast; however, this vaccine would be administered in two doses over 1 month, as opposed to three doses over 6 months as is the schedule for currently approved vaccines. Both manufacturing representatives and approving members of the committee stressed this as an important factor due to vaccination dropout rates.
“We have a problem with hepatitis B infections in this country as well as problems with the current vaccines,“ said John Ward, MD, director of the division of viral hepatitis at the Centers for Disease Control and Prevention, “and they happen in these populations where, in terms of data, both of those audiences have problems about going for the second and third dose.”
Patients that drop out before the third dose are at high risk of infection, as only 20%-50% of adults have the appropriate seroprotection after two doses. However, only 54% of patients in a vaccine safety Datalink study reported completing the vaccination series, with 81% reporting having received two doses, according to Dr. Schaffner.
While the committee did approve the safety research as sufficient to approve use of Heplisav-B in adults 18 years and older, members of the committee had an issue with the drug’s correlation with myocardial infarction.
In one of the studies presented, Heplisav-B’s acute myocardial infarction (AMI) events (14 patients) greatly outnumbered those of Engerix-B (1 patient), presenting an AMI relative risk of 6.97.
Dynavax representatives, in response to this concern, presented intention to conduct a postmarketing analysis of the risk of MI in patients who have been administered Heplisav-B, which committee members considered to be a crucial contingency for approval.
“I would like to say I am for the approval of this vaccine, I just think as a statistician that the safety was inconclusive,” said Mei-Ling Ting Lee, PhD, director of the Biostatistics and Risk Assessment Center at the University of Maryland. “But I think for the pharmacological vigilance plan, I think that it will be good to have specific analysis for the myocardial infarction and other risks.”
Dynavax intends to introduce the vaccine commercially in the United States by the middle of 2018, according to a press release.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
The Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee approved licensure for Heplisav-B, a new two-dose recombinant hepatitis B vaccination, after voting that presented data proved the vaccine to be safe for adults 18 and over.
At an advisory meeting, after hearing testimony from government researchers and representatives of Dynavax Technologies Corporation, the manufacturer of Heplisav-B, 11 members voted to approve the drug, 1 member voted no, and 3 abstained.
There are more than 20,000 new infections each year, with a reported increase of 21% between 2014 and 2015, according to research presented by William Schaffner, MD, professor of preventative medicine and infectious diseases at Vanderbilt University, Nashville, Tenn.
There are two approved immunizations for hepatitis B: Engerix-B, manufactured by GlaxoSmithKline, and Recombivax HB, by Merck. Both are three-dose, recombinant vaccines produced from yeast cells.
Like the current vaccines, Heplisav-B is a recombinant hepatitis B surface antigen that is derived from yeast; however, this vaccine would be administered in two doses over 1 month, as opposed to three doses over 6 months as is the schedule for currently approved vaccines. Both manufacturing representatives and approving members of the committee stressed this as an important factor due to vaccination dropout rates.
“We have a problem with hepatitis B infections in this country as well as problems with the current vaccines,“ said John Ward, MD, director of the division of viral hepatitis at the Centers for Disease Control and Prevention, “and they happen in these populations where, in terms of data, both of those audiences have problems about going for the second and third dose.”
Patients that drop out before the third dose are at high risk of infection, as only 20%-50% of adults have the appropriate seroprotection after two doses. However, only 54% of patients in a vaccine safety Datalink study reported completing the vaccination series, with 81% reporting having received two doses, according to Dr. Schaffner.
While the committee did approve the safety research as sufficient to approve use of Heplisav-B in adults 18 years and older, members of the committee had an issue with the drug’s correlation with myocardial infarction.
In one of the studies presented, Heplisav-B’s acute myocardial infarction (AMI) events (14 patients) greatly outnumbered those of Engerix-B (1 patient), presenting an AMI relative risk of 6.97.
Dynavax representatives, in response to this concern, presented intention to conduct a postmarketing analysis of the risk of MI in patients who have been administered Heplisav-B, which committee members considered to be a crucial contingency for approval.
“I would like to say I am for the approval of this vaccine, I just think as a statistician that the safety was inconclusive,” said Mei-Ling Ting Lee, PhD, director of the Biostatistics and Risk Assessment Center at the University of Maryland. “But I think for the pharmacological vigilance plan, I think that it will be good to have specific analysis for the myocardial infarction and other risks.”
Dynavax intends to introduce the vaccine commercially in the United States by the middle of 2018, according to a press release.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
NLR useful for predicting 1-year mortality in PBC patients
An elevated baseline neutrophil-to-lymphocyte ratio (NLR) was associated with a poor 1-year mortality rate in hospitalized primary biliary cholangitis (PBC) patients, according to Lin Lin, MD, of Tianjin (China) Medical University General Hospital and the Tianjin Institute of Digestive Diseases and associates.
A retrospective analysis of 88 PBC patients hospitalized between June 2009 and January 2014 was performed for the study. NLR was a significant predictor of survival, with an odds ratio of 1.5, a sensitivity of 100%, and a specificity of 67.1%. A baseline NLR value of 2.18 was selected as the cutoff for 1-year mortality. Of the 33 patients above this value at initial hospitalization, 6 died, whereas none of the 55 patients below this value died.
The results of the retrospective study were confirmed in a prospective 1-year cohort that included 63 people with PBC. The patients with a baseline NLR of less than 2.18 had significantly longer survival times than those who had a baseline NLR of 2.18 or higher.
“NLR – an affordable, widely available and reproducible index – is closely related to short-term mortality in patients with PBC. Further studies are warranted to externally cross-validate our findings in other populations,” the investigators concluded.
Find the full study in BMJ Open (2017. doi: 10.1136/bmjopen-2016-015304).
An elevated baseline neutrophil-to-lymphocyte ratio (NLR) was associated with a poor 1-year mortality rate in hospitalized primary biliary cholangitis (PBC) patients, according to Lin Lin, MD, of Tianjin (China) Medical University General Hospital and the Tianjin Institute of Digestive Diseases and associates.
A retrospective analysis of 88 PBC patients hospitalized between June 2009 and January 2014 was performed for the study. NLR was a significant predictor of survival, with an odds ratio of 1.5, a sensitivity of 100%, and a specificity of 67.1%. A baseline NLR value of 2.18 was selected as the cutoff for 1-year mortality. Of the 33 patients above this value at initial hospitalization, 6 died, whereas none of the 55 patients below this value died.
The results of the retrospective study were confirmed in a prospective 1-year cohort that included 63 people with PBC. The patients with a baseline NLR of less than 2.18 had significantly longer survival times than those who had a baseline NLR of 2.18 or higher.
“NLR – an affordable, widely available and reproducible index – is closely related to short-term mortality in patients with PBC. Further studies are warranted to externally cross-validate our findings in other populations,” the investigators concluded.
Find the full study in BMJ Open (2017. doi: 10.1136/bmjopen-2016-015304).
An elevated baseline neutrophil-to-lymphocyte ratio (NLR) was associated with a poor 1-year mortality rate in hospitalized primary biliary cholangitis (PBC) patients, according to Lin Lin, MD, of Tianjin (China) Medical University General Hospital and the Tianjin Institute of Digestive Diseases and associates.
A retrospective analysis of 88 PBC patients hospitalized between June 2009 and January 2014 was performed for the study. NLR was a significant predictor of survival, with an odds ratio of 1.5, a sensitivity of 100%, and a specificity of 67.1%. A baseline NLR value of 2.18 was selected as the cutoff for 1-year mortality. Of the 33 patients above this value at initial hospitalization, 6 died, whereas none of the 55 patients below this value died.
The results of the retrospective study were confirmed in a prospective 1-year cohort that included 63 people with PBC. The patients with a baseline NLR of less than 2.18 had significantly longer survival times than those who had a baseline NLR of 2.18 or higher.
“NLR – an affordable, widely available and reproducible index – is closely related to short-term mortality in patients with PBC. Further studies are warranted to externally cross-validate our findings in other populations,” the investigators concluded.
Find the full study in BMJ Open (2017. doi: 10.1136/bmjopen-2016-015304).
FROM BMJ OPEN
Hepatitis B elimination: Is it possible?
Despite the availability of safe and effective vaccines for more than three decades, the 2017 World Health Organization (WHO) Global Hepatitis Report estimated that worldwide more than 250 million persons are chronically infected with hepatitis B virus (www.who.int/hepatitis/publications/global-hepatitis-report2017/). In the United States, as many as 2.2 million persons may be chronically infected but only one-third are aware of their infection. In 2015, the WHO declared that hepatitis B and C should be eliminated as public health problems by the year 2030. In March 2017, the National Academies of Science, Engineering and Medicine (NASEM) set targets for HBV elimination in the United States by 2030 as follows: 50% reduction in deaths, 45% reduction in cirrhosis, and 33% reduction in hepatocellular carcinoma (HCC) compared to 2015. For these targets, 90% of persons chronically infected need to be diagnosed, 90% of those diagnosed linked to care, and treatment initiated in 80% of those with treatment indications. In addition, new infections among children should be eliminated through complete prevention of mother-to-child transmission.
For persons who are chronically infected, antiviral therapy can suppress HBV replication, reduce hepatic inflammation, reverse hepatic fibrosis, and prevent progression to cirrhosis, hepatic decompensation, and HCC. However, currently approved treatments are associated with low rates of hepatitis B surface antigen (HBsAg) clearance and decreased but continued risk of HCC. New treatments aimed at cure are desired but complete cure of HBV may not be feasible as HBV persists in the liver even in patients with serologic recovery after transient acute HBV infection.
Functional cure aimed at restoring chronic hepatitis B patients to a state akin to those with spontaneous HBsAg clearance might be a more realistic goal. With improved understanding of the biology of HBV, including recent identification of its entry receptor, better in vitro and animal models, and revival of interest in hepatitis B research, it is conceivable that combinations of antiviral targeting different steps in HBV life cyle and immunomodulatory therapies aimed to boost T-cell response to HBV and/or remove inhibitory signals can result in functional cure (HBsAg clearance) in a high percentage of patients after a finite course of treatment (Hepatology 2017; in press).
The HBV elimination goals set by WHO and NASEM are lofty, but as both organizations stated, these goals are feasible if all stakeholders make elimination of HBV a priority and allocate resources to make it happen.
Dr. Lok is the Alice Lohrman Andrews Research Professor in Hepatology in the department of internal medicine, University of Michigan Health System in Ann Arbor. Her comments were made during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.
Despite the availability of safe and effective vaccines for more than three decades, the 2017 World Health Organization (WHO) Global Hepatitis Report estimated that worldwide more than 250 million persons are chronically infected with hepatitis B virus (www.who.int/hepatitis/publications/global-hepatitis-report2017/). In the United States, as many as 2.2 million persons may be chronically infected but only one-third are aware of their infection. In 2015, the WHO declared that hepatitis B and C should be eliminated as public health problems by the year 2030. In March 2017, the National Academies of Science, Engineering and Medicine (NASEM) set targets for HBV elimination in the United States by 2030 as follows: 50% reduction in deaths, 45% reduction in cirrhosis, and 33% reduction in hepatocellular carcinoma (HCC) compared to 2015. For these targets, 90% of persons chronically infected need to be diagnosed, 90% of those diagnosed linked to care, and treatment initiated in 80% of those with treatment indications. In addition, new infections among children should be eliminated through complete prevention of mother-to-child transmission.
For persons who are chronically infected, antiviral therapy can suppress HBV replication, reduce hepatic inflammation, reverse hepatic fibrosis, and prevent progression to cirrhosis, hepatic decompensation, and HCC. However, currently approved treatments are associated with low rates of hepatitis B surface antigen (HBsAg) clearance and decreased but continued risk of HCC. New treatments aimed at cure are desired but complete cure of HBV may not be feasible as HBV persists in the liver even in patients with serologic recovery after transient acute HBV infection.
Functional cure aimed at restoring chronic hepatitis B patients to a state akin to those with spontaneous HBsAg clearance might be a more realistic goal. With improved understanding of the biology of HBV, including recent identification of its entry receptor, better in vitro and animal models, and revival of interest in hepatitis B research, it is conceivable that combinations of antiviral targeting different steps in HBV life cyle and immunomodulatory therapies aimed to boost T-cell response to HBV and/or remove inhibitory signals can result in functional cure (HBsAg clearance) in a high percentage of patients after a finite course of treatment (Hepatology 2017; in press).
The HBV elimination goals set by WHO and NASEM are lofty, but as both organizations stated, these goals are feasible if all stakeholders make elimination of HBV a priority and allocate resources to make it happen.
Dr. Lok is the Alice Lohrman Andrews Research Professor in Hepatology in the department of internal medicine, University of Michigan Health System in Ann Arbor. Her comments were made during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.
Despite the availability of safe and effective vaccines for more than three decades, the 2017 World Health Organization (WHO) Global Hepatitis Report estimated that worldwide more than 250 million persons are chronically infected with hepatitis B virus (www.who.int/hepatitis/publications/global-hepatitis-report2017/). In the United States, as many as 2.2 million persons may be chronically infected but only one-third are aware of their infection. In 2015, the WHO declared that hepatitis B and C should be eliminated as public health problems by the year 2030. In March 2017, the National Academies of Science, Engineering and Medicine (NASEM) set targets for HBV elimination in the United States by 2030 as follows: 50% reduction in deaths, 45% reduction in cirrhosis, and 33% reduction in hepatocellular carcinoma (HCC) compared to 2015. For these targets, 90% of persons chronically infected need to be diagnosed, 90% of those diagnosed linked to care, and treatment initiated in 80% of those with treatment indications. In addition, new infections among children should be eliminated through complete prevention of mother-to-child transmission.
For persons who are chronically infected, antiviral therapy can suppress HBV replication, reduce hepatic inflammation, reverse hepatic fibrosis, and prevent progression to cirrhosis, hepatic decompensation, and HCC. However, currently approved treatments are associated with low rates of hepatitis B surface antigen (HBsAg) clearance and decreased but continued risk of HCC. New treatments aimed at cure are desired but complete cure of HBV may not be feasible as HBV persists in the liver even in patients with serologic recovery after transient acute HBV infection.
Functional cure aimed at restoring chronic hepatitis B patients to a state akin to those with spontaneous HBsAg clearance might be a more realistic goal. With improved understanding of the biology of HBV, including recent identification of its entry receptor, better in vitro and animal models, and revival of interest in hepatitis B research, it is conceivable that combinations of antiviral targeting different steps in HBV life cyle and immunomodulatory therapies aimed to boost T-cell response to HBV and/or remove inhibitory signals can result in functional cure (HBsAg clearance) in a high percentage of patients after a finite course of treatment (Hepatology 2017; in press).
The HBV elimination goals set by WHO and NASEM are lofty, but as both organizations stated, these goals are feasible if all stakeholders make elimination of HBV a priority and allocate resources to make it happen.
Dr. Lok is the Alice Lohrman Andrews Research Professor in Hepatology in the department of internal medicine, University of Michigan Health System in Ann Arbor. Her comments were made during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.
Acute liver failure in the ED
Acute liver failure (ALF), is a life-threatening deterioration of liver function in people without preexisting cirrhosis. It can be caused by acetaminophen toxicity, pregnancy, ischemia, hepatitis A infection, and Wilson disease, among other things.
In emergency medicine, ALF can pose serious dilemmas. While transplantation has drastically improved survival rates in recent decades, it is not always required, and no firm criteria for transplantation exist.
But delays in the decision to go ahead with a liver transplant can lead to death.
A new literature review aims to distill the decision-making process for emergency medicine practitioners. Knowing which candidates will benefit and when to perform transplantation “is crucial in improving the likelihood of survival,” its authors say, because of the many factors involved.
In a paper published online in May in The American Journal of Emergency Medicine (2017 May. doi. 10.1016/j.ajem.2017.05.028), Hamid Shokoohi, MD, and his colleagues at George Washington University Medical Center in Washington say that establishing the cause of acute liver failure is essential to making treatment decisions, as some causes are associated with poorer prognosis without transplantation.
“We wanted to improve awareness among emergency medicine physicians, who are the first in the chain of command for transferring patients to a transplant site,” said Ali Pourmand, MD, of George Washington University, Washington, and the corresponding author of the study. “The high risk of early death among these cases makes it necessary for emergency physicians to consider coexisting etiology, be aware of indications and criteria available to determine the need for emergent transplantation, and be able to expedite patient transfer to a transplant center, when indicated.”
As patients presenting with ALF are likely too impaired be able to provide a history, and physical exam findings may be nonspecific, laboratory findings are key in establishing both severity and likely cause. ALF patients in general will have a prolonged prothrombin time, markedly elevated aminotransferase levels, elevated bilirubin, and low platelet count.
Patients with ALF caused by acetaminophen toxicity (the most common cause of ALF in the United States) are likely to present with very high aminotransferase levels, low bilirubin, and high international normalized ratio (INR). Those with viral causes of ALF, meanwhile, tend to have aminotransferase levels of 1,000-2,000 IU/L, and alanine transaminase higher than aspartate transaminase.
Prognosis without transplantation is considerably poorer in patients with severe ALF caused by Wilson disease, Budd-Chiari syndrome, or idiosyncratic drug reactions, compared with those who experience viral hepatitis or acetaminophen toxicity.
Dr. Shokoohi and his colleagues noted that two validated scoring systems can be used to assess prognosis for severe ALF. The King’s College Criteria can be used to establish prognosis for ALF caused by acetaminophen, and ALF from other causes, while the MELD score, recommended by the American Association for the Study of Liver Diseases, incorporates bilirubin, INR, sodium, and creatinine levels to predict prognosis. Both of these scoring systems can be used to inform decisions about transplantation.
Finally, the authors advised that patients with alcoholic liver disease be considered under the same criteria for transplantation as those with other causes of ALF. “Recent research has shown that only a minority of patients ... will have poor follow-up and noncompliance to therapy and/or will revert to heavy alcohol use or abuse after transplant,” they wrote in their analysis. The researchers disclosed no outside funding of conflicts of interest related to their article.
Acute liver failure (ALF), is a life-threatening deterioration of liver function in people without preexisting cirrhosis. It can be caused by acetaminophen toxicity, pregnancy, ischemia, hepatitis A infection, and Wilson disease, among other things.
In emergency medicine, ALF can pose serious dilemmas. While transplantation has drastically improved survival rates in recent decades, it is not always required, and no firm criteria for transplantation exist.
But delays in the decision to go ahead with a liver transplant can lead to death.
A new literature review aims to distill the decision-making process for emergency medicine practitioners. Knowing which candidates will benefit and when to perform transplantation “is crucial in improving the likelihood of survival,” its authors say, because of the many factors involved.
In a paper published online in May in The American Journal of Emergency Medicine (2017 May. doi. 10.1016/j.ajem.2017.05.028), Hamid Shokoohi, MD, and his colleagues at George Washington University Medical Center in Washington say that establishing the cause of acute liver failure is essential to making treatment decisions, as some causes are associated with poorer prognosis without transplantation.
“We wanted to improve awareness among emergency medicine physicians, who are the first in the chain of command for transferring patients to a transplant site,” said Ali Pourmand, MD, of George Washington University, Washington, and the corresponding author of the study. “The high risk of early death among these cases makes it necessary for emergency physicians to consider coexisting etiology, be aware of indications and criteria available to determine the need for emergent transplantation, and be able to expedite patient transfer to a transplant center, when indicated.”
As patients presenting with ALF are likely too impaired be able to provide a history, and physical exam findings may be nonspecific, laboratory findings are key in establishing both severity and likely cause. ALF patients in general will have a prolonged prothrombin time, markedly elevated aminotransferase levels, elevated bilirubin, and low platelet count.
Patients with ALF caused by acetaminophen toxicity (the most common cause of ALF in the United States) are likely to present with very high aminotransferase levels, low bilirubin, and high international normalized ratio (INR). Those with viral causes of ALF, meanwhile, tend to have aminotransferase levels of 1,000-2,000 IU/L, and alanine transaminase higher than aspartate transaminase.
Prognosis without transplantation is considerably poorer in patients with severe ALF caused by Wilson disease, Budd-Chiari syndrome, or idiosyncratic drug reactions, compared with those who experience viral hepatitis or acetaminophen toxicity.
Dr. Shokoohi and his colleagues noted that two validated scoring systems can be used to assess prognosis for severe ALF. The King’s College Criteria can be used to establish prognosis for ALF caused by acetaminophen, and ALF from other causes, while the MELD score, recommended by the American Association for the Study of Liver Diseases, incorporates bilirubin, INR, sodium, and creatinine levels to predict prognosis. Both of these scoring systems can be used to inform decisions about transplantation.
Finally, the authors advised that patients with alcoholic liver disease be considered under the same criteria for transplantation as those with other causes of ALF. “Recent research has shown that only a minority of patients ... will have poor follow-up and noncompliance to therapy and/or will revert to heavy alcohol use or abuse after transplant,” they wrote in their analysis. The researchers disclosed no outside funding of conflicts of interest related to their article.
Acute liver failure (ALF), is a life-threatening deterioration of liver function in people without preexisting cirrhosis. It can be caused by acetaminophen toxicity, pregnancy, ischemia, hepatitis A infection, and Wilson disease, among other things.
In emergency medicine, ALF can pose serious dilemmas. While transplantation has drastically improved survival rates in recent decades, it is not always required, and no firm criteria for transplantation exist.
But delays in the decision to go ahead with a liver transplant can lead to death.
A new literature review aims to distill the decision-making process for emergency medicine practitioners. Knowing which candidates will benefit and when to perform transplantation “is crucial in improving the likelihood of survival,” its authors say, because of the many factors involved.
In a paper published online in May in The American Journal of Emergency Medicine (2017 May. doi. 10.1016/j.ajem.2017.05.028), Hamid Shokoohi, MD, and his colleagues at George Washington University Medical Center in Washington say that establishing the cause of acute liver failure is essential to making treatment decisions, as some causes are associated with poorer prognosis without transplantation.
“We wanted to improve awareness among emergency medicine physicians, who are the first in the chain of command for transferring patients to a transplant site,” said Ali Pourmand, MD, of George Washington University, Washington, and the corresponding author of the study. “The high risk of early death among these cases makes it necessary for emergency physicians to consider coexisting etiology, be aware of indications and criteria available to determine the need for emergent transplantation, and be able to expedite patient transfer to a transplant center, when indicated.”
As patients presenting with ALF are likely too impaired be able to provide a history, and physical exam findings may be nonspecific, laboratory findings are key in establishing both severity and likely cause. ALF patients in general will have a prolonged prothrombin time, markedly elevated aminotransferase levels, elevated bilirubin, and low platelet count.
Patients with ALF caused by acetaminophen toxicity (the most common cause of ALF in the United States) are likely to present with very high aminotransferase levels, low bilirubin, and high international normalized ratio (INR). Those with viral causes of ALF, meanwhile, tend to have aminotransferase levels of 1,000-2,000 IU/L, and alanine transaminase higher than aspartate transaminase.
Prognosis without transplantation is considerably poorer in patients with severe ALF caused by Wilson disease, Budd-Chiari syndrome, or idiosyncratic drug reactions, compared with those who experience viral hepatitis or acetaminophen toxicity.
Dr. Shokoohi and his colleagues noted that two validated scoring systems can be used to assess prognosis for severe ALF. The King’s College Criteria can be used to establish prognosis for ALF caused by acetaminophen, and ALF from other causes, while the MELD score, recommended by the American Association for the Study of Liver Diseases, incorporates bilirubin, INR, sodium, and creatinine levels to predict prognosis. Both of these scoring systems can be used to inform decisions about transplantation.
Finally, the authors advised that patients with alcoholic liver disease be considered under the same criteria for transplantation as those with other causes of ALF. “Recent research has shown that only a minority of patients ... will have poor follow-up and noncompliance to therapy and/or will revert to heavy alcohol use or abuse after transplant,” they wrote in their analysis. The researchers disclosed no outside funding of conflicts of interest related to their article.
FROM THE AMERICAN JOURNAL OF EMERGENCY MEDICINE
FDA approves new treatment for adults with HCV
The Food and Drug Administration announced on July 18 the approval of Vosevi to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis or with mild cirrhosis.
Vosevi is now the first treatment for patients who have been previously treated with the direct-acting antiviral drug sofosbuvir or other drugs for HCV that inhibit a protein called NS5A. The new drug is a fixed-dose, combination tablet containing sofosbuvir and velpatasvir (both approved before) and a new drug – voxilaprevir.
It is noted that treatment recommendations for Vosevi are different depending on viral genotype and prior treatment history. Vosevi is contraindicated in patients taking the drug rifampin.
“Direct-acting antiviral drugs prevent the virus from multiplying and often cure HCV. Vosevi provides a treatment option for some patients who were not successfully treated with other HCV drugs in the past,” Edward Cox, MD, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in a press release.
Read the full press release on the FDA’s website.
The Food and Drug Administration announced on July 18 the approval of Vosevi to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis or with mild cirrhosis.
Vosevi is now the first treatment for patients who have been previously treated with the direct-acting antiviral drug sofosbuvir or other drugs for HCV that inhibit a protein called NS5A. The new drug is a fixed-dose, combination tablet containing sofosbuvir and velpatasvir (both approved before) and a new drug – voxilaprevir.
It is noted that treatment recommendations for Vosevi are different depending on viral genotype and prior treatment history. Vosevi is contraindicated in patients taking the drug rifampin.
“Direct-acting antiviral drugs prevent the virus from multiplying and often cure HCV. Vosevi provides a treatment option for some patients who were not successfully treated with other HCV drugs in the past,” Edward Cox, MD, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in a press release.
Read the full press release on the FDA’s website.
The Food and Drug Administration announced on July 18 the approval of Vosevi to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis or with mild cirrhosis.
Vosevi is now the first treatment for patients who have been previously treated with the direct-acting antiviral drug sofosbuvir or other drugs for HCV that inhibit a protein called NS5A. The new drug is a fixed-dose, combination tablet containing sofosbuvir and velpatasvir (both approved before) and a new drug – voxilaprevir.
It is noted that treatment recommendations for Vosevi are different depending on viral genotype and prior treatment history. Vosevi is contraindicated in patients taking the drug rifampin.
“Direct-acting antiviral drugs prevent the virus from multiplying and often cure HCV. Vosevi provides a treatment option for some patients who were not successfully treated with other HCV drugs in the past,” Edward Cox, MD, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in a press release.
Read the full press release on the FDA’s website.