Liver Disease

Patients with nonalcoholic steatohepatitis (NASH) and advanced fibrosis reported lower quality of life that is worsened in those who develop cirrhosis, based on data from 1,667 individuals.

NASH is becoming an increasingly common cause of liver disease, cirrhosis, and hepatocellular carcinoma and can have a negative effect on patients’ quality of life and other patient-reported outcomes (PROs), but studies of the impact on PROs in these patients are limited, wrote Zobair M. Younossi, MD, of the Inova Health System, Falls Church, Va., and colleagues.

In a study published in Clinical Gastroenterology and Hepatology, the researchers reviewed data from 870 adults with NASH cirrhosis and 797 with NASH and bridging fibrosis. The average age of the patients was 58 years, 73% were white, 40% were male, 52% had cirrhosis, and 74% had diabetes.

The researchers used four tools to assess quality of life: the SF-36 (36-Item Short Form Health Survey), the EQ-5D (Euroqol, a generic health questionnaire), the CLDQ-NASH (Chronic Liver Disease Questionnaire-NASH), and the WPAI:SHP (Work Productivity and Activity Impairment: Specific Health Problem).

The SF-36 score is based on eight domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health.

Overall, patients with NASH and cirrhosis had significantly lower scores on domains of the SF-36 that related to physical function, compared with bridging fibrosis patients (70.3 vs. 73.6), as well as role physical (71.6 vs. 75.4) and bodily pain (65.0 vs. 68.6). The other areas of significant impairment in NASH patients with cirrhosis, compared with NASH patients with fibrosis, appeared in four domains of the disease-specific CLDQ-NASH: activity, emotional, fatigue, and worry. In addition, the EQ-5D utility score was significantly lower in cirrhosis patients, compared with fibrosis patients.

Older age, male sex, Asian race, and U.S. location of study enrollment were independent predictors of higher PRO scores in a multivariate analysis, while black race, history of smoking, history of diabetes, higher body mass index, cirrhosis, and history of comorbidities that were gastrointestinal, musculoskeletal, psychiatric, or neurologic were independent predictors of lower PRO scores in patients with advanced fibrosis and NASH.

WPAI:SHP scores, which focused on work productivity impairment and absenteeism, were not significantly different between the groups.

The study findings were limited by several factors including the specific nature of the study population and absence of non-NASH controls, the potential of false positives because of the use of self-reports, and the lack of longitudinal data, the researchers said. The results should be verified in a larger, diverse patient population, the researchers noted, but the data highlight the impairment in quality of life and productivity among patients with NASH and “can inform patients, clinicians, payers, and policymakers about the total burden of the disease and also the comprehensive benefit of treatment,” they concluded.

The study was supported by Gilead Sciences. Dr. Younossi disclosed relationships with Gilead Sciences, as well as Intercept, NovoNordisk, BMS, Allergan/Tobira, Terns, Viking, AbbVie, Novartis, and Quest Diagnostics.

SOURCE: Younossi ZM et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.02.024.

Patients with nonalcoholic steatohepatitis (NASH) and advanced fibrosis reported lower quality of life that is worsened in those who develop cirrhosis, based on data from 1,667 individuals.

NASH is becoming an increasingly common cause of liver disease, cirrhosis, and hepatocellular carcinoma and can have a negative effect on patients’ quality of life and other patient-reported outcomes (PROs), but studies of the impact on PROs in these patients are limited, wrote Zobair M. Younossi, MD, of the Inova Health System, Falls Church, Va., and colleagues.

In a study published in Clinical Gastroenterology and Hepatology, the researchers reviewed data from 870 adults with NASH cirrhosis and 797 with NASH and bridging fibrosis. The average age of the patients was 58 years, 73% were white, 40% were male, 52% had cirrhosis, and 74% had diabetes.

The researchers used four tools to assess quality of life: the SF-36 (36-Item Short Form Health Survey), the EQ-5D (Euroqol, a generic health questionnaire), the CLDQ-NASH (Chronic Liver Disease Questionnaire-NASH), and the WPAI:SHP (Work Productivity and Activity Impairment: Specific Health Problem).

The SF-36 score is based on eight domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health.

Overall, patients with NASH and cirrhosis had significantly lower scores on domains of the SF-36 that related to physical function, compared with bridging fibrosis patients (70.3 vs. 73.6), as well as role physical (71.6 vs. 75.4) and bodily pain (65.0 vs. 68.6). The other areas of significant impairment in NASH patients with cirrhosis, compared with NASH patients with fibrosis, appeared in four domains of the disease-specific CLDQ-NASH: activity, emotional, fatigue, and worry. In addition, the EQ-5D utility score was significantly lower in cirrhosis patients, compared with fibrosis patients.

Older age, male sex, Asian race, and U.S. location of study enrollment were independent predictors of higher PRO scores in a multivariate analysis, while black race, history of smoking, history of diabetes, higher body mass index, cirrhosis, and history of comorbidities that were gastrointestinal, musculoskeletal, psychiatric, or neurologic were independent predictors of lower PRO scores in patients with advanced fibrosis and NASH.

WPAI:SHP scores, which focused on work productivity impairment and absenteeism, were not significantly different between the groups.

The study findings were limited by several factors including the specific nature of the study population and absence of non-NASH controls, the potential of false positives because of the use of self-reports, and the lack of longitudinal data, the researchers said. The results should be verified in a larger, diverse patient population, the researchers noted, but the data highlight the impairment in quality of life and productivity among patients with NASH and “can inform patients, clinicians, payers, and policymakers about the total burden of the disease and also the comprehensive benefit of treatment,” they concluded.

The study was supported by Gilead Sciences. Dr. Younossi disclosed relationships with Gilead Sciences, as well as Intercept, NovoNordisk, BMS, Allergan/Tobira, Terns, Viking, AbbVie, Novartis, and Quest Diagnostics.

SOURCE: Younossi ZM et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.02.024.

Patients with nonalcoholic steatohepatitis (NASH) and advanced fibrosis reported lower quality of life that is worsened in those who develop cirrhosis, based on data from 1,667 individuals.

NASH is becoming an increasingly common cause of liver disease, cirrhosis, and hepatocellular carcinoma and can have a negative effect on patients’ quality of life and other patient-reported outcomes (PROs), but studies of the impact on PROs in these patients are limited, wrote Zobair M. Younossi, MD, of the Inova Health System, Falls Church, Va., and colleagues.

In a study published in Clinical Gastroenterology and Hepatology, the researchers reviewed data from 870 adults with NASH cirrhosis and 797 with NASH and bridging fibrosis. The average age of the patients was 58 years, 73% were white, 40% were male, 52% had cirrhosis, and 74% had diabetes.

The researchers used four tools to assess quality of life: the SF-36 (36-Item Short Form Health Survey), the EQ-5D (Euroqol, a generic health questionnaire), the CLDQ-NASH (Chronic Liver Disease Questionnaire-NASH), and the WPAI:SHP (Work Productivity and Activity Impairment: Specific Health Problem).

The SF-36 score is based on eight domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health.

Overall, patients with NASH and cirrhosis had significantly lower scores on domains of the SF-36 that related to physical function, compared with bridging fibrosis patients (70.3 vs. 73.6), as well as role physical (71.6 vs. 75.4) and bodily pain (65.0 vs. 68.6). The other areas of significant impairment in NASH patients with cirrhosis, compared with NASH patients with fibrosis, appeared in four domains of the disease-specific CLDQ-NASH: activity, emotional, fatigue, and worry. In addition, the EQ-5D utility score was significantly lower in cirrhosis patients, compared with fibrosis patients.

Older age, male sex, Asian race, and U.S. location of study enrollment were independent predictors of higher PRO scores in a multivariate analysis, while black race, history of smoking, history of diabetes, higher body mass index, cirrhosis, and history of comorbidities that were gastrointestinal, musculoskeletal, psychiatric, or neurologic were independent predictors of lower PRO scores in patients with advanced fibrosis and NASH.

WPAI:SHP scores, which focused on work productivity impairment and absenteeism, were not significantly different between the groups.

The study findings were limited by several factors including the specific nature of the study population and absence of non-NASH controls, the potential of false positives because of the use of self-reports, and the lack of longitudinal data, the researchers said. The results should be verified in a larger, diverse patient population, the researchers noted, but the data highlight the impairment in quality of life and productivity among patients with NASH and “can inform patients, clinicians, payers, and policymakers about the total burden of the disease and also the comprehensive benefit of treatment,” they concluded.

The study was supported by Gilead Sciences. Dr. Younossi disclosed relationships with Gilead Sciences, as well as Intercept, NovoNordisk, BMS, Allergan/Tobira, Terns, Viking, AbbVie, Novartis, and Quest Diagnostics.

SOURCE: Younossi ZM et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.02.024.

Direct-acting antiviral (DAA) therapy significantly reduced the risk of death in patients with hepatitis C infections and a history of hepatocellular carcinoma, based on data from 797 individuals.

Previous studies have reported a benefit of direct-acting antiviral (DAA) therapy for reducing mortality in patients with hepatocellular carcinoma (HCC), but data on its impact in patients with complete responses to HCC therapy are limited, wrote Amit G. Singal, MD, of the University of Texas, Dallas, and colleagues.

In a study published in Gastroenterology, the researchers identified adult HCC patients who achieved complete treatment response between January 2013 and December 2017. The study included patients from 31 locations in the United States and Canada. Complete response to treatment was defined as “disappearance of arterial enhancement from all HCC lesions on contrast-enhanced cross-sectional imaging.”

A total of 383 (48.1%) of patients were randomized to DAA therapy, and 414 (51.9%) did not receive DAA treatment for their HCV infection after complete response to prior HCC therapy.

A total of 43 deaths occurred among DAA patients over 941 person-years of follow-up, compared with 103 deaths over 527 person-years of follow-up for the untreated controls. Overall, DAA therapy was associated with a significantly reduced risk of death (hazard ratio, 0.54), compared with no therapy. Of note, patients with a sustained virologic response showed a reduced risk of death (HR, 0.29), but those without a sustained virologic response to DAA therapy did not (HR, 1.13).

The findings support those from previous studies suggesting that DAA therapy may reduce mortality in patients with a history of HCC, the researchers said.

The study findings were limited by several factors, including potential confounding if DAA was given to patients with better prognoses, the researchers noted. Other limitations include the use of imaging in routine clinical care rather than centralized review, the loss of approximately 9% of the patients to follow-up, and the lack of data on hepatic decompensation during follow-up, the researchers said. However, the results were strengthened by the multicenter design, large cohort, and inclusion of untreated controls, and support the use of DAA therapies as “likely beneficial in HCV-infected patients with a history of HCC,” they concluded.

The study was funded in part by the National Cancer Institute and AbbVie. Dr. Singal disclosed relationships with companies including AbbVie, Gilead, Bayer, Eisai, Wako Diagnostics, Exact Sciences, Exelixis, Roche, Glycotest, and Bristol-Myers Squibb.

SOURCE: Singal AG et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.07.040.

Direct-acting antiviral (DAA) therapy significantly reduced the risk of death in patients with hepatitis C infections and a history of hepatocellular carcinoma, based on data from 797 individuals.

Previous studies have reported a benefit of direct-acting antiviral (DAA) therapy for reducing mortality in patients with hepatocellular carcinoma (HCC), but data on its impact in patients with complete responses to HCC therapy are limited, wrote Amit G. Singal, MD, of the University of Texas, Dallas, and colleagues.

In a study published in Gastroenterology, the researchers identified adult HCC patients who achieved complete treatment response between January 2013 and December 2017. The study included patients from 31 locations in the United States and Canada. Complete response to treatment was defined as “disappearance of arterial enhancement from all HCC lesions on contrast-enhanced cross-sectional imaging.”

A total of 383 (48.1%) of patients were randomized to DAA therapy, and 414 (51.9%) did not receive DAA treatment for their HCV infection after complete response to prior HCC therapy.

A total of 43 deaths occurred among DAA patients over 941 person-years of follow-up, compared with 103 deaths over 527 person-years of follow-up for the untreated controls. Overall, DAA therapy was associated with a significantly reduced risk of death (hazard ratio, 0.54), compared with no therapy. Of note, patients with a sustained virologic response showed a reduced risk of death (HR, 0.29), but those without a sustained virologic response to DAA therapy did not (HR, 1.13).

The findings support those from previous studies suggesting that DAA therapy may reduce mortality in patients with a history of HCC, the researchers said.

The study findings were limited by several factors, including potential confounding if DAA was given to patients with better prognoses, the researchers noted. Other limitations include the use of imaging in routine clinical care rather than centralized review, the loss of approximately 9% of the patients to follow-up, and the lack of data on hepatic decompensation during follow-up, the researchers said. However, the results were strengthened by the multicenter design, large cohort, and inclusion of untreated controls, and support the use of DAA therapies as “likely beneficial in HCV-infected patients with a history of HCC,” they concluded.

The study was funded in part by the National Cancer Institute and AbbVie. Dr. Singal disclosed relationships with companies including AbbVie, Gilead, Bayer, Eisai, Wako Diagnostics, Exact Sciences, Exelixis, Roche, Glycotest, and Bristol-Myers Squibb.

SOURCE: Singal AG et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.07.040.

Direct-acting antiviral (DAA) therapy significantly reduced the risk of death in patients with hepatitis C infections and a history of hepatocellular carcinoma, based on data from 797 individuals.

Previous studies have reported a benefit of direct-acting antiviral (DAA) therapy for reducing mortality in patients with hepatocellular carcinoma (HCC), but data on its impact in patients with complete responses to HCC therapy are limited, wrote Amit G. Singal, MD, of the University of Texas, Dallas, and colleagues.

In a study published in Gastroenterology, the researchers identified adult HCC patients who achieved complete treatment response between January 2013 and December 2017. The study included patients from 31 locations in the United States and Canada. Complete response to treatment was defined as “disappearance of arterial enhancement from all HCC lesions on contrast-enhanced cross-sectional imaging.”

A total of 383 (48.1%) of patients were randomized to DAA therapy, and 414 (51.9%) did not receive DAA treatment for their HCV infection after complete response to prior HCC therapy.

A total of 43 deaths occurred among DAA patients over 941 person-years of follow-up, compared with 103 deaths over 527 person-years of follow-up for the untreated controls. Overall, DAA therapy was associated with a significantly reduced risk of death (hazard ratio, 0.54), compared with no therapy. Of note, patients with a sustained virologic response showed a reduced risk of death (HR, 0.29), but those without a sustained virologic response to DAA therapy did not (HR, 1.13).

The findings support those from previous studies suggesting that DAA therapy may reduce mortality in patients with a history of HCC, the researchers said.

The study findings were limited by several factors, including potential confounding if DAA was given to patients with better prognoses, the researchers noted. Other limitations include the use of imaging in routine clinical care rather than centralized review, the loss of approximately 9% of the patients to follow-up, and the lack of data on hepatic decompensation during follow-up, the researchers said. However, the results were strengthened by the multicenter design, large cohort, and inclusion of untreated controls, and support the use of DAA therapies as “likely beneficial in HCV-infected patients with a history of HCC,” they concluded.

The study was funded in part by the National Cancer Institute and AbbVie. Dr. Singal disclosed relationships with companies including AbbVie, Gilead, Bayer, Eisai, Wako Diagnostics, Exact Sciences, Exelixis, Roche, Glycotest, and Bristol-Myers Squibb.

SOURCE: Singal AG et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.07.040.

A new study involving both human patients and mice has confirmed a long-believed association between nonalcoholic fatty liver disease (NAFLD) and an alteration in the gut microbiome that produces high levels of alcohol.

NIAID

The study was initiated after the treatment of a rare case: a patient who presented with severe nonalcoholic steatohepatitis (NASH) plus auto-brewery syndrome. The patient had a very high blood alcohol concentration but an alcohol-free, high-carbohydrate diet. It was determined that strains of high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) rather than a fungal infection were the catalyst for the high blood alcohol level. As such, Jing Yuan of the Capital Institute of Pediatrics in Beijing and coauthors attempted to “connect these commensal HiAlc Kpn to the pathogenesis of hepatic damage” through this study, which was published in Cell Metabolism.

The researchers began by examining 43 patients with NAFLD and 48 healthy controls. Among the patients with NAFLD, 11 had nonalcoholic fatty liver and 32 had NASH. Specifically, they analyzed the presence and effects of HiAlc Kpn, determining that the abundance of Klebsiella pneumoniae was slightly higher in the feces of NAFLD patients, compared with healthy patients, but that their alcohol-producing ability in NAFLD patients was significantly stronger. Of the patients with NAFLD, 61% carried HiAlc and medium-alcohol-producing Kpn, compared with 6.25% of the controls.

Another phase of their study involved feeding specific pathogen-free mice either HiAlc Kpn, ethanol, or yeast extract peptone dextrose medium (pair-fed) for 4, 6, and 8 weeks. The mice that were fed HiAlc Kpn or ethanol showed clear microsteatosis and macrosteatosis in their livers at 4 and 8 weeks, compared with the pair-fed mice. In addition, the HiAlc-Kpn-fed and ethanol-fed mice had increased levels of aspartate transaminase and alanine transaminase in their serum and increased levels of triglycerides and thiobarbituric acid reactive substances in their liver. The results overall indicated that the HiAlc-Kpn-fed mice had developed hepatic steatosis.

An additional phase included the intestinal flora from a NASH patient with a specific Kpn strain being fed to germ-free mice. At the same time, two types of intestinal flora from mice with NAFLD were transplanted into healthy mice: one induced by two other specific Kpn strains and one in which those strains had been selectively eliminated. The results saw obvious steatosis in the mice who received the flora from either mice with NAFLD induced by Kpn or the NASH patient at 4 weeks and 8 weeks, respectively. The mice who received the flora win which Kpn had been eliminated saw no fat-related changes in the liver. “These results further suggest that HiAlc Kpn might be one of the major causes of NAFLD development,” the researchers wrote.

The authors acknowledged the study’s limitations, chiefly including the lack of a clinical cohort of individuals with auto brewery syndrome but without NAFLD that could be used as a control. However, they also noted a belief that “causality was shown by the transfer experiments of HiAlc Kpn” while adding that “the further analysis of the impact of ethanol in ABS [auto brewery syndrome] patients should be investigated.”

The study was funded by grants from the National Natural Science Foundation for Key Programs of China, the National Natural Science Foundation of China, Megaprojects of Science and Technology Research of China, and CAMS Innovation Fund for Medical Sciences. The authors reported no conflicts of interest.
 

SOURCE: Yuan J et al. Cell Metab. 2019 Sep 19. doi: 10.1016/j.cmet.2019.08.018.

A new study involving both human patients and mice has confirmed a long-believed association between nonalcoholic fatty liver disease (NAFLD) and an alteration in the gut microbiome that produces high levels of alcohol.

NIAID

The study was initiated after the treatment of a rare case: a patient who presented with severe nonalcoholic steatohepatitis (NASH) plus auto-brewery syndrome. The patient had a very high blood alcohol concentration but an alcohol-free, high-carbohydrate diet. It was determined that strains of high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) rather than a fungal infection were the catalyst for the high blood alcohol level. As such, Jing Yuan of the Capital Institute of Pediatrics in Beijing and coauthors attempted to “connect these commensal HiAlc Kpn to the pathogenesis of hepatic damage” through this study, which was published in Cell Metabolism.

The researchers began by examining 43 patients with NAFLD and 48 healthy controls. Among the patients with NAFLD, 11 had nonalcoholic fatty liver and 32 had NASH. Specifically, they analyzed the presence and effects of HiAlc Kpn, determining that the abundance of Klebsiella pneumoniae was slightly higher in the feces of NAFLD patients, compared with healthy patients, but that their alcohol-producing ability in NAFLD patients was significantly stronger. Of the patients with NAFLD, 61% carried HiAlc and medium-alcohol-producing Kpn, compared with 6.25% of the controls.

Another phase of their study involved feeding specific pathogen-free mice either HiAlc Kpn, ethanol, or yeast extract peptone dextrose medium (pair-fed) for 4, 6, and 8 weeks. The mice that were fed HiAlc Kpn or ethanol showed clear microsteatosis and macrosteatosis in their livers at 4 and 8 weeks, compared with the pair-fed mice. In addition, the HiAlc-Kpn-fed and ethanol-fed mice had increased levels of aspartate transaminase and alanine transaminase in their serum and increased levels of triglycerides and thiobarbituric acid reactive substances in their liver. The results overall indicated that the HiAlc-Kpn-fed mice had developed hepatic steatosis.

An additional phase included the intestinal flora from a NASH patient with a specific Kpn strain being fed to germ-free mice. At the same time, two types of intestinal flora from mice with NAFLD were transplanted into healthy mice: one induced by two other specific Kpn strains and one in which those strains had been selectively eliminated. The results saw obvious steatosis in the mice who received the flora from either mice with NAFLD induced by Kpn or the NASH patient at 4 weeks and 8 weeks, respectively. The mice who received the flora win which Kpn had been eliminated saw no fat-related changes in the liver. “These results further suggest that HiAlc Kpn might be one of the major causes of NAFLD development,” the researchers wrote.

The authors acknowledged the study’s limitations, chiefly including the lack of a clinical cohort of individuals with auto brewery syndrome but without NAFLD that could be used as a control. However, they also noted a belief that “causality was shown by the transfer experiments of HiAlc Kpn” while adding that “the further analysis of the impact of ethanol in ABS [auto brewery syndrome] patients should be investigated.”

The study was funded by grants from the National Natural Science Foundation for Key Programs of China, the National Natural Science Foundation of China, Megaprojects of Science and Technology Research of China, and CAMS Innovation Fund for Medical Sciences. The authors reported no conflicts of interest.
 

SOURCE: Yuan J et al. Cell Metab. 2019 Sep 19. doi: 10.1016/j.cmet.2019.08.018.

A new study involving both human patients and mice has confirmed a long-believed association between nonalcoholic fatty liver disease (NAFLD) and an alteration in the gut microbiome that produces high levels of alcohol.

NIAID

The study was initiated after the treatment of a rare case: a patient who presented with severe nonalcoholic steatohepatitis (NASH) plus auto-brewery syndrome. The patient had a very high blood alcohol concentration but an alcohol-free, high-carbohydrate diet. It was determined that strains of high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) rather than a fungal infection were the catalyst for the high blood alcohol level. As such, Jing Yuan of the Capital Institute of Pediatrics in Beijing and coauthors attempted to “connect these commensal HiAlc Kpn to the pathogenesis of hepatic damage” through this study, which was published in Cell Metabolism.

The researchers began by examining 43 patients with NAFLD and 48 healthy controls. Among the patients with NAFLD, 11 had nonalcoholic fatty liver and 32 had NASH. Specifically, they analyzed the presence and effects of HiAlc Kpn, determining that the abundance of Klebsiella pneumoniae was slightly higher in the feces of NAFLD patients, compared with healthy patients, but that their alcohol-producing ability in NAFLD patients was significantly stronger. Of the patients with NAFLD, 61% carried HiAlc and medium-alcohol-producing Kpn, compared with 6.25% of the controls.

Another phase of their study involved feeding specific pathogen-free mice either HiAlc Kpn, ethanol, or yeast extract peptone dextrose medium (pair-fed) for 4, 6, and 8 weeks. The mice that were fed HiAlc Kpn or ethanol showed clear microsteatosis and macrosteatosis in their livers at 4 and 8 weeks, compared with the pair-fed mice. In addition, the HiAlc-Kpn-fed and ethanol-fed mice had increased levels of aspartate transaminase and alanine transaminase in their serum and increased levels of triglycerides and thiobarbituric acid reactive substances in their liver. The results overall indicated that the HiAlc-Kpn-fed mice had developed hepatic steatosis.

An additional phase included the intestinal flora from a NASH patient with a specific Kpn strain being fed to germ-free mice. At the same time, two types of intestinal flora from mice with NAFLD were transplanted into healthy mice: one induced by two other specific Kpn strains and one in which those strains had been selectively eliminated. The results saw obvious steatosis in the mice who received the flora from either mice with NAFLD induced by Kpn or the NASH patient at 4 weeks and 8 weeks, respectively. The mice who received the flora win which Kpn had been eliminated saw no fat-related changes in the liver. “These results further suggest that HiAlc Kpn might be one of the major causes of NAFLD development,” the researchers wrote.

The authors acknowledged the study’s limitations, chiefly including the lack of a clinical cohort of individuals with auto brewery syndrome but without NAFLD that could be used as a control. However, they also noted a belief that “causality was shown by the transfer experiments of HiAlc Kpn” while adding that “the further analysis of the impact of ethanol in ABS [auto brewery syndrome] patients should be investigated.”

The study was funded by grants from the National Natural Science Foundation for Key Programs of China, the National Natural Science Foundation of China, Megaprojects of Science and Technology Research of China, and CAMS Innovation Fund for Medical Sciences. The authors reported no conflicts of interest.
 

SOURCE: Yuan J et al. Cell Metab. 2019 Sep 19. doi: 10.1016/j.cmet.2019.08.018.

Medical comorbidity burden is significantly associated with 6-month and overall mortality in individuals with suspected drug-induced liver injury (DILI). In addition, a model consisting of Charlson Comorbidity Index, model for end-stage liver disease score, and serum albumin strongly predicts 6-month mortality in patients with suspected DILI.

Those are key findings from a study which set out to investigate the association between comorbidity burden and outcomes of patients with DILI and to develop a model to calculate risk of death within 6 months.

“Drug-induced liver injury is an important cause of liver-related morbidity and mortality that is likely under-recognized,” investigators led by Marwan S. Ghabril, MD, of the division of gastroenterology and hepatology at Indiana University, Indianapolis, wrote in a study published in Gastroenterology. “Its diagnosis depends on high index of suspicion, compatible temporal relationship, and thorough exclusion of competing etiologies. DILI by an implicated drug commonly occurs in patients with one or several comorbid conditions such as hypertension, diabetes mellitus, cardiovascular disease, renal disease, and malignancy. However, the impact of comorbidity burden on mortality in patients with suspected DILI has not been previously investigated.”

For the current analysis and model development, the researchers drew from 306 patients enrolled in the multicenter Drug-Induced Liver Injury Network Prospective Study at Indiana University between 2003 and 2017 (discovery cohort; Drug Saf. 2009;32:55-68). To validate their model, they used data from 247 patients who were enrolled in the same study at the University of North Carolina (validation cohort). The primary outcome of interest was mortality within 6 months of onset of liver injury.

The mean ages of the discovery and validation cohorts were 49 years and 51 years, respectively. Dr. Ghabril and colleagues found that 6-month mortality was 8.5% in the discovery cohort and 4.5% in the validation cohort. “The most common class of implicated agent was antimicrobials with no significant differences between groups,” they wrote. “However, herbal and dietary supplements were predominantly implicated in patients with none to mild comorbidity, while cardiovascular agents were predominantly implicated in patients with significant comorbidity.”

Among patients in the discovery cohort, the presence of significant comorbidities, defined as a Charlson Comorbidity Index score greater than 2, was independently associated with 6-month mortality (odds ratio, 5.22), as was model for end-stage liver disease score (OR, 1.11) and serum level of albumin at presentation (OR, 0.39). When the researchers created a morbidity risk model based on those three clinical variables, it performed well, identifying patients who died within 6 months with a C statistic value of 0.89 in the discovery cohort and 0.91 in the validation cohort. This spurred the development of a web-based risk calculator, which clinicians can access at http://gihep.com/calculators/hepatology/dili-cam/.

“Since DILI is not a unique cause of liver injury, it is conceivable that models incorporating comorbidity burden and severity of liver injury could prove useful in improving the prediction of mortality in a variety of liver injuries and diseases, and as such warrants further studies,” the researchers wrote.

The study was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Ghabril reported having no financial disclosures, but two coauthors reported having numerous financial ties to industry.

[email protected]

SOURCE: Ghabril M et al. Gastroenterology. 2019 Jul 11. doi: 10/1053/j.gastro.2019.07.006.

Medical comorbidity burden is significantly associated with 6-month and overall mortality in individuals with suspected drug-induced liver injury (DILI). In addition, a model consisting of Charlson Comorbidity Index, model for end-stage liver disease score, and serum albumin strongly predicts 6-month mortality in patients with suspected DILI.

Those are key findings from a study which set out to investigate the association between comorbidity burden and outcomes of patients with DILI and to develop a model to calculate risk of death within 6 months.

“Drug-induced liver injury is an important cause of liver-related morbidity and mortality that is likely under-recognized,” investigators led by Marwan S. Ghabril, MD, of the division of gastroenterology and hepatology at Indiana University, Indianapolis, wrote in a study published in Gastroenterology. “Its diagnosis depends on high index of suspicion, compatible temporal relationship, and thorough exclusion of competing etiologies. DILI by an implicated drug commonly occurs in patients with one or several comorbid conditions such as hypertension, diabetes mellitus, cardiovascular disease, renal disease, and malignancy. However, the impact of comorbidity burden on mortality in patients with suspected DILI has not been previously investigated.”

For the current analysis and model development, the researchers drew from 306 patients enrolled in the multicenter Drug-Induced Liver Injury Network Prospective Study at Indiana University between 2003 and 2017 (discovery cohort; Drug Saf. 2009;32:55-68). To validate their model, they used data from 247 patients who were enrolled in the same study at the University of North Carolina (validation cohort). The primary outcome of interest was mortality within 6 months of onset of liver injury.

The mean ages of the discovery and validation cohorts were 49 years and 51 years, respectively. Dr. Ghabril and colleagues found that 6-month mortality was 8.5% in the discovery cohort and 4.5% in the validation cohort. “The most common class of implicated agent was antimicrobials with no significant differences between groups,” they wrote. “However, herbal and dietary supplements were predominantly implicated in patients with none to mild comorbidity, while cardiovascular agents were predominantly implicated in patients with significant comorbidity.”

Among patients in the discovery cohort, the presence of significant comorbidities, defined as a Charlson Comorbidity Index score greater than 2, was independently associated with 6-month mortality (odds ratio, 5.22), as was model for end-stage liver disease score (OR, 1.11) and serum level of albumin at presentation (OR, 0.39). When the researchers created a morbidity risk model based on those three clinical variables, it performed well, identifying patients who died within 6 months with a C statistic value of 0.89 in the discovery cohort and 0.91 in the validation cohort. This spurred the development of a web-based risk calculator, which clinicians can access at http://gihep.com/calculators/hepatology/dili-cam/.

“Since DILI is not a unique cause of liver injury, it is conceivable that models incorporating comorbidity burden and severity of liver injury could prove useful in improving the prediction of mortality in a variety of liver injuries and diseases, and as such warrants further studies,” the researchers wrote.

The study was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Ghabril reported having no financial disclosures, but two coauthors reported having numerous financial ties to industry.

[email protected]

SOURCE: Ghabril M et al. Gastroenterology. 2019 Jul 11. doi: 10/1053/j.gastro.2019.07.006.

Medical comorbidity burden is significantly associated with 6-month and overall mortality in individuals with suspected drug-induced liver injury (DILI). In addition, a model consisting of Charlson Comorbidity Index, model for end-stage liver disease score, and serum albumin strongly predicts 6-month mortality in patients with suspected DILI.

Those are key findings from a study which set out to investigate the association between comorbidity burden and outcomes of patients with DILI and to develop a model to calculate risk of death within 6 months.

“Drug-induced liver injury is an important cause of liver-related morbidity and mortality that is likely under-recognized,” investigators led by Marwan S. Ghabril, MD, of the division of gastroenterology and hepatology at Indiana University, Indianapolis, wrote in a study published in Gastroenterology. “Its diagnosis depends on high index of suspicion, compatible temporal relationship, and thorough exclusion of competing etiologies. DILI by an implicated drug commonly occurs in patients with one or several comorbid conditions such as hypertension, diabetes mellitus, cardiovascular disease, renal disease, and malignancy. However, the impact of comorbidity burden on mortality in patients with suspected DILI has not been previously investigated.”

For the current analysis and model development, the researchers drew from 306 patients enrolled in the multicenter Drug-Induced Liver Injury Network Prospective Study at Indiana University between 2003 and 2017 (discovery cohort; Drug Saf. 2009;32:55-68). To validate their model, they used data from 247 patients who were enrolled in the same study at the University of North Carolina (validation cohort). The primary outcome of interest was mortality within 6 months of onset of liver injury.

The mean ages of the discovery and validation cohorts were 49 years and 51 years, respectively. Dr. Ghabril and colleagues found that 6-month mortality was 8.5% in the discovery cohort and 4.5% in the validation cohort. “The most common class of implicated agent was antimicrobials with no significant differences between groups,” they wrote. “However, herbal and dietary supplements were predominantly implicated in patients with none to mild comorbidity, while cardiovascular agents were predominantly implicated in patients with significant comorbidity.”

Among patients in the discovery cohort, the presence of significant comorbidities, defined as a Charlson Comorbidity Index score greater than 2, was independently associated with 6-month mortality (odds ratio, 5.22), as was model for end-stage liver disease score (OR, 1.11) and serum level of albumin at presentation (OR, 0.39). When the researchers created a morbidity risk model based on those three clinical variables, it performed well, identifying patients who died within 6 months with a C statistic value of 0.89 in the discovery cohort and 0.91 in the validation cohort. This spurred the development of a web-based risk calculator, which clinicians can access at http://gihep.com/calculators/hepatology/dili-cam/.

“Since DILI is not a unique cause of liver injury, it is conceivable that models incorporating comorbidity burden and severity of liver injury could prove useful in improving the prediction of mortality in a variety of liver injuries and diseases, and as such warrants further studies,” the researchers wrote.

The study was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Ghabril reported having no financial disclosures, but two coauthors reported having numerous financial ties to industry.

[email protected]

SOURCE: Ghabril M et al. Gastroenterology. 2019 Jul 11. doi: 10/1053/j.gastro.2019.07.006.

A new supercooling process could extend ex vivo liver viability by more than a day, potentially expanding transplant availability, according to investigators.

Massachusetts General Hospital

Standard cooling to 4°C provides just 12 hours of organ preservation, but laboratory testing showed that supercooling to –4°C added 27 hours of viability, reported lead author Reinier J. de Vries, MD, of Harvard Medical School and Massachusetts General Hospital in Boston, and colleagues.

“The absence of technology to preserve organs for more than a few hours is one of the fundamental causes of the donor organ–shortage crisis,” the investigators wrote in Nature Biotechnology.

Supercooling organs to high-subzero temperatures has been shown to prolong organ life while avoiding ice-mediated injury, but techniques that are successful for rat livers have been difficult to translate to human livers because of their larger size, which increases the risk of ice formation, the investigators explained.

Three strategies were employed to overcome this problem: minimization of air-liquid interfaces, development of a new supercooling-preservation solution, and hypothermic machine perfusion to more evenly distribute preservation solution throughout the liver tissue. For recovery of organs after supercooling, the investigators used subnormothermic machine perfusion, which has been used effectively in rat transplants.

In order to measure the impact of this process on organ viability, the investigators first measured adenylate energy content, both before supercooling and after recovery.

“Adenylate energy content, and, particularly, the organ’s ability to recover it during (re)perfusion, is considered the most representative metric for liver viability,” they wrote.

The difference between pre- and postsupercooling energy charge was less than 20%; in comparison, failed liver transplants in large animals and clinical trials have typically involved an energy-charge loss of 40% or more.

To further test organ viability, the investigators measured pre- and postsupercooling levels of bile production, oxygen uptake, and vascular resistance. All of these parameters have been shown to predict transplant success in rats, and bile production has additional precedent from human studies.

On average, bile production, portal resistance, and arterial resistance were not significantly affected by supercooling. Although portal vein resistance was 20% higher after supercooling, this compared favorably with increases of 100%-150% that have been measured in nonviable livers. Similarly, oxygen uptake increased by a mean of 17%, but this was three times lower than changes that have been observed in livers with impaired viability, at 51%.

Additional measures of hepatocellular injury, including AST and ALT, were also supportive of viability after supercooling. Histopathology confirmed these findings by showing preserved tissue architecture.

“In summary, we find that the human livers tested displayed no substantial difference in viability before and after extended subzero supercooling preservation,” the investigators wrote.

To simulate transplantation, the investigators reperfused the organs with blood at a normal temperature, including platelets, complement, and white blood cells, which are drivers of ischemia reperfusion injury. During this process, energy charge remained stable, which indicates preserved mitochondrial function. While energy charge held steady, lactate metabolism increased with bile and urea production, suggesting increased liver function. Bile pH and HCO_3– levels fell within range for viability. Although bile glucose exceeded proposed criteria, the investigators pointed out that levels still fell within parameters for research-quality livers. Lactate levels also rose within the first hour of reperfusion, but the investigators suggested that this finding should be interpreted with appropriate context.

“It should be considered that the livers in this study were initially rejected for transplantation,” they wrote, “and the confidence intervals of the lactate concentration at the end of reperfusion largely overlap with time-matched values reported by others during [normothermic machine perfusion] of rejected human livers.”

Hepatocellular injury and histology also were evaluated during and after simulated transplantation, respectively, with favorable results. Although sites of preexisting hepatic injury were aggravated by the process, and rates of apoptosis increased, the investigators considered these changes were clinically insignificant.

Looking to the future, the investigators suggested that further refinement of the process could facilitate even-lower storage temperatures while better preserving liver viability.

“The use of human livers makes this study clinically relevant and promotes the translation of subzero organ preservation to the clinic,” the investigators concluded. “However, long-term survival experiments of transplanted supercooled livers in swine or an alternative large animal model will be needed before clinical translation.”

The study was funded by the National Institutes of Health and the Department of Defense. Dr. de Vries and four other coauthors have provisional patent applications related to the study, and one coauthor disclosed a financial relationship with Organ Solutions.

SOURCE: de Vries RJ et al. Nature Biotechnol. 2019 Sep 9. doi: 10.1038/s41587-019-0223-y.

A new supercooling process could extend ex vivo liver viability by more than a day, potentially expanding transplant availability, according to investigators.

Massachusetts General Hospital

Standard cooling to 4°C provides just 12 hours of organ preservation, but laboratory testing showed that supercooling to –4°C added 27 hours of viability, reported lead author Reinier J. de Vries, MD, of Harvard Medical School and Massachusetts General Hospital in Boston, and colleagues.

“The absence of technology to preserve organs for more than a few hours is one of the fundamental causes of the donor organ–shortage crisis,” the investigators wrote in Nature Biotechnology.

Supercooling organs to high-subzero temperatures has been shown to prolong organ life while avoiding ice-mediated injury, but techniques that are successful for rat livers have been difficult to translate to human livers because of their larger size, which increases the risk of ice formation, the investigators explained.

Three strategies were employed to overcome this problem: minimization of air-liquid interfaces, development of a new supercooling-preservation solution, and hypothermic machine perfusion to more evenly distribute preservation solution throughout the liver tissue. For recovery of organs after supercooling, the investigators used subnormothermic machine perfusion, which has been used effectively in rat transplants.

In order to measure the impact of this process on organ viability, the investigators first measured adenylate energy content, both before supercooling and after recovery.

“Adenylate energy content, and, particularly, the organ’s ability to recover it during (re)perfusion, is considered the most representative metric for liver viability,” they wrote.

The difference between pre- and postsupercooling energy charge was less than 20%; in comparison, failed liver transplants in large animals and clinical trials have typically involved an energy-charge loss of 40% or more.

To further test organ viability, the investigators measured pre- and postsupercooling levels of bile production, oxygen uptake, and vascular resistance. All of these parameters have been shown to predict transplant success in rats, and bile production has additional precedent from human studies.

On average, bile production, portal resistance, and arterial resistance were not significantly affected by supercooling. Although portal vein resistance was 20% higher after supercooling, this compared favorably with increases of 100%-150% that have been measured in nonviable livers. Similarly, oxygen uptake increased by a mean of 17%, but this was three times lower than changes that have been observed in livers with impaired viability, at 51%.

Additional measures of hepatocellular injury, including AST and ALT, were also supportive of viability after supercooling. Histopathology confirmed these findings by showing preserved tissue architecture.

“In summary, we find that the human livers tested displayed no substantial difference in viability before and after extended subzero supercooling preservation,” the investigators wrote.

To simulate transplantation, the investigators reperfused the organs with blood at a normal temperature, including platelets, complement, and white blood cells, which are drivers of ischemia reperfusion injury. During this process, energy charge remained stable, which indicates preserved mitochondrial function. While energy charge held steady, lactate metabolism increased with bile and urea production, suggesting increased liver function. Bile pH and HCO_3– levels fell within range for viability. Although bile glucose exceeded proposed criteria, the investigators pointed out that levels still fell within parameters for research-quality livers. Lactate levels also rose within the first hour of reperfusion, but the investigators suggested that this finding should be interpreted with appropriate context.

“It should be considered that the livers in this study were initially rejected for transplantation,” they wrote, “and the confidence intervals of the lactate concentration at the end of reperfusion largely overlap with time-matched values reported by others during [normothermic machine perfusion] of rejected human livers.”

Hepatocellular injury and histology also were evaluated during and after simulated transplantation, respectively, with favorable results. Although sites of preexisting hepatic injury were aggravated by the process, and rates of apoptosis increased, the investigators considered these changes were clinically insignificant.

Looking to the future, the investigators suggested that further refinement of the process could facilitate even-lower storage temperatures while better preserving liver viability.

“The use of human livers makes this study clinically relevant and promotes the translation of subzero organ preservation to the clinic,” the investigators concluded. “However, long-term survival experiments of transplanted supercooled livers in swine or an alternative large animal model will be needed before clinical translation.”

The study was funded by the National Institutes of Health and the Department of Defense. Dr. de Vries and four other coauthors have provisional patent applications related to the study, and one coauthor disclosed a financial relationship with Organ Solutions.

SOURCE: de Vries RJ et al. Nature Biotechnol. 2019 Sep 9. doi: 10.1038/s41587-019-0223-y.

A new supercooling process could extend ex vivo liver viability by more than a day, potentially expanding transplant availability, according to investigators.

Massachusetts General Hospital

Standard cooling to 4°C provides just 12 hours of organ preservation, but laboratory testing showed that supercooling to –4°C added 27 hours of viability, reported lead author Reinier J. de Vries, MD, of Harvard Medical School and Massachusetts General Hospital in Boston, and colleagues.

“The absence of technology to preserve organs for more than a few hours is one of the fundamental causes of the donor organ–shortage crisis,” the investigators wrote in Nature Biotechnology.

Supercooling organs to high-subzero temperatures has been shown to prolong organ life while avoiding ice-mediated injury, but techniques that are successful for rat livers have been difficult to translate to human livers because of their larger size, which increases the risk of ice formation, the investigators explained.

Three strategies were employed to overcome this problem: minimization of air-liquid interfaces, development of a new supercooling-preservation solution, and hypothermic machine perfusion to more evenly distribute preservation solution throughout the liver tissue. For recovery of organs after supercooling, the investigators used subnormothermic machine perfusion, which has been used effectively in rat transplants.

In order to measure the impact of this process on organ viability, the investigators first measured adenylate energy content, both before supercooling and after recovery.

“Adenylate energy content, and, particularly, the organ’s ability to recover it during (re)perfusion, is considered the most representative metric for liver viability,” they wrote.

The difference between pre- and postsupercooling energy charge was less than 20%; in comparison, failed liver transplants in large animals and clinical trials have typically involved an energy-charge loss of 40% or more.

To further test organ viability, the investigators measured pre- and postsupercooling levels of bile production, oxygen uptake, and vascular resistance. All of these parameters have been shown to predict transplant success in rats, and bile production has additional precedent from human studies.

On average, bile production, portal resistance, and arterial resistance were not significantly affected by supercooling. Although portal vein resistance was 20% higher after supercooling, this compared favorably with increases of 100%-150% that have been measured in nonviable livers. Similarly, oxygen uptake increased by a mean of 17%, but this was three times lower than changes that have been observed in livers with impaired viability, at 51%.

Additional measures of hepatocellular injury, including AST and ALT, were also supportive of viability after supercooling. Histopathology confirmed these findings by showing preserved tissue architecture.

“In summary, we find that the human livers tested displayed no substantial difference in viability before and after extended subzero supercooling preservation,” the investigators wrote.

To simulate transplantation, the investigators reperfused the organs with blood at a normal temperature, including platelets, complement, and white blood cells, which are drivers of ischemia reperfusion injury. During this process, energy charge remained stable, which indicates preserved mitochondrial function. While energy charge held steady, lactate metabolism increased with bile and urea production, suggesting increased liver function. Bile pH and HCO_3– levels fell within range for viability. Although bile glucose exceeded proposed criteria, the investigators pointed out that levels still fell within parameters for research-quality livers. Lactate levels also rose within the first hour of reperfusion, but the investigators suggested that this finding should be interpreted with appropriate context.

“It should be considered that the livers in this study were initially rejected for transplantation,” they wrote, “and the confidence intervals of the lactate concentration at the end of reperfusion largely overlap with time-matched values reported by others during [normothermic machine perfusion] of rejected human livers.”

Hepatocellular injury and histology also were evaluated during and after simulated transplantation, respectively, with favorable results. Although sites of preexisting hepatic injury were aggravated by the process, and rates of apoptosis increased, the investigators considered these changes were clinically insignificant.

Looking to the future, the investigators suggested that further refinement of the process could facilitate even-lower storage temperatures while better preserving liver viability.

“The use of human livers makes this study clinically relevant and promotes the translation of subzero organ preservation to the clinic,” the investigators concluded. “However, long-term survival experiments of transplanted supercooled livers in swine or an alternative large animal model will be needed before clinical translation.”

The study was funded by the National Institutes of Health and the Department of Defense. Dr. de Vries and four other coauthors have provisional patent applications related to the study, and one coauthor disclosed a financial relationship with Organ Solutions.

SOURCE: de Vries RJ et al. Nature Biotechnol. 2019 Sep 9. doi: 10.1038/s41587-019-0223-y.

Patients with viral hepatitis may live longer after treatment with direct-acting antiviral agents (DAAs), but their risk of extrahepatic causes of death may rise as a result, according to investigators.

Importantly, this increasing rate of extrahepatic mortality shouldn’t be seen as a causal link with DAA use, cautioned lead author Donghee Kim, MD, PhD, of Stanford (Calif.) University, and colleagues. Instead, the upward trend is more likely because of successful treatment with DAAs, which can increase lifespan, and with it, time for susceptibility to extrahepatic conditions.

This was just one finding from a retrospective study that used U.S. Census and National Center for Health Statistics mortality records to evaluate almost 28 million deaths that occurred between 2007 and 2017. The investigators looked for mortality trends among patients with common chronic liver diseases, including viral hepatitis, alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD), noting that each of these conditions is associated with extrahepatic complications. The study included deaths due to extrahepatic cancer, cardiovascular disease, and diabetes.

While the efficacy of therapy for viral hepatitis has improved markedly since 2014, treatments for ALD and NAFLD have remained static, the investigators noted.

“Unfortunately, there have been no significant breakthroughs in the treatment of [ALD] over the last 2 decades, resulting in an increase in estimated global mortality to 3.8%,” the investigators wrote in Gastroenterology.

“[NAFLD] is the most common chronic liver disease in the world,” they added. “The leading cause of death in individuals with NAFLD is cardiovascular disease, followed by extrahepatic malignancies, and then liver-related mortality. However, recent trends in ALD and NAFLD-related extrahepatic complications in comparison to viral hepatitis have not been studied.”

The results of the current study supported the positive impact of DAAs, which began to see widespread use in 2014. Age-standardized mortality among patients with hepatitis C virus rose until 2014 (2.2% per year) and dropped thereafter (–6.5% per year). Mortality among those with hepatitis B virus steadily decreased over the study period (–1.2% per year).

Of note, while deaths because of HCV-related liver disease dropped from 2014 to 2017, extrahepatic causes of death didn’t follow suit. Age-standardized mortality for cardiovascular disease and diabetes increased at average annual rates of 1.9% and 3.3%, respectively, while the rate of extrahepatic cancer-related deaths held steady.

“The widespread use, higher efficacy and durable response to DAA agents in individuals with HCV infection may have resulted in a paradigm shift in the clinical progression of coexisting disease entities following response to DAA agents in the virus-free environment,” the investigators wrote. “These findings suggest assessment and identification of risk and risk factors for extrahepatic cancer, cardiovascular disease, and diabetes in individuals who have been successfully treated and cured of HCV infection.”

In sharp contrast with the viral hepatitis findings, mortality rates among patients with ALD and NAFLD increased at an accelerating rate over the 11-year study period.

Among patients with ALD, all-cause mortality increased by an average of 3.4% per year, at a higher rate in the second half of the study than the first (4.6% vs 2.1%). Liver disease–related mortality rose at a similar, accelerating rate. In the same group, deaths due to cardiovascular disease increased at an average annual rate of 2.1%, which was accelerating, while extrahepatic cancer-related deaths increased at a more constant rate of 3.6%.

For patients with NAFLD, all-cause mortality increased by 8.1% per year, accelerating from 6.1% in the first half of the study to 11.2% in the second. Deaths from liver disease increased at an average rate of 12.6% per year, while extrahepatic deaths increased significantly for all three included types: cardiovascular disease (2.0%), extrahepatic cancer (15.1%), and diabetes (9.7%).

Concerning the worsening rates of mortality among patients with ALD and NAFLD, the investigators cited a lack of progress in treatments, and suggested that “the quest for newer therapies must remain the cornerstone in our efforts.”

The investigators reported no external funding or conflicts of interest.

SOURCE: Kim D et al. Gastroenterology. 2019 Jun 25. doi: 10.1053/j.gastro.2019.06.026.

Patients with viral hepatitis may live longer after treatment with direct-acting antiviral agents (DAAs), but their risk of extrahepatic causes of death may rise as a result, according to investigators.

Importantly, this increasing rate of extrahepatic mortality shouldn’t be seen as a causal link with DAA use, cautioned lead author Donghee Kim, MD, PhD, of Stanford (Calif.) University, and colleagues. Instead, the upward trend is more likely because of successful treatment with DAAs, which can increase lifespan, and with it, time for susceptibility to extrahepatic conditions.

This was just one finding from a retrospective study that used U.S. Census and National Center for Health Statistics mortality records to evaluate almost 28 million deaths that occurred between 2007 and 2017. The investigators looked for mortality trends among patients with common chronic liver diseases, including viral hepatitis, alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD), noting that each of these conditions is associated with extrahepatic complications. The study included deaths due to extrahepatic cancer, cardiovascular disease, and diabetes.

While the efficacy of therapy for viral hepatitis has improved markedly since 2014, treatments for ALD and NAFLD have remained static, the investigators noted.

“Unfortunately, there have been no significant breakthroughs in the treatment of [ALD] over the last 2 decades, resulting in an increase in estimated global mortality to 3.8%,” the investigators wrote in Gastroenterology.

“[NAFLD] is the most common chronic liver disease in the world,” they added. “The leading cause of death in individuals with NAFLD is cardiovascular disease, followed by extrahepatic malignancies, and then liver-related mortality. However, recent trends in ALD and NAFLD-related extrahepatic complications in comparison to viral hepatitis have not been studied.”

The results of the current study supported the positive impact of DAAs, which began to see widespread use in 2014. Age-standardized mortality among patients with hepatitis C virus rose until 2014 (2.2% per year) and dropped thereafter (–6.5% per year). Mortality among those with hepatitis B virus steadily decreased over the study period (–1.2% per year).

Of note, while deaths because of HCV-related liver disease dropped from 2014 to 2017, extrahepatic causes of death didn’t follow suit. Age-standardized mortality for cardiovascular disease and diabetes increased at average annual rates of 1.9% and 3.3%, respectively, while the rate of extrahepatic cancer-related deaths held steady.

“The widespread use, higher efficacy and durable response to DAA agents in individuals with HCV infection may have resulted in a paradigm shift in the clinical progression of coexisting disease entities following response to DAA agents in the virus-free environment,” the investigators wrote. “These findings suggest assessment and identification of risk and risk factors for extrahepatic cancer, cardiovascular disease, and diabetes in individuals who have been successfully treated and cured of HCV infection.”

In sharp contrast with the viral hepatitis findings, mortality rates among patients with ALD and NAFLD increased at an accelerating rate over the 11-year study period.

Among patients with ALD, all-cause mortality increased by an average of 3.4% per year, at a higher rate in the second half of the study than the first (4.6% vs 2.1%). Liver disease–related mortality rose at a similar, accelerating rate. In the same group, deaths due to cardiovascular disease increased at an average annual rate of 2.1%, which was accelerating, while extrahepatic cancer-related deaths increased at a more constant rate of 3.6%.

For patients with NAFLD, all-cause mortality increased by 8.1% per year, accelerating from 6.1% in the first half of the study to 11.2% in the second. Deaths from liver disease increased at an average rate of 12.6% per year, while extrahepatic deaths increased significantly for all three included types: cardiovascular disease (2.0%), extrahepatic cancer (15.1%), and diabetes (9.7%).

Concerning the worsening rates of mortality among patients with ALD and NAFLD, the investigators cited a lack of progress in treatments, and suggested that “the quest for newer therapies must remain the cornerstone in our efforts.”

The investigators reported no external funding or conflicts of interest.

SOURCE: Kim D et al. Gastroenterology. 2019 Jun 25. doi: 10.1053/j.gastro.2019.06.026.

Patients with viral hepatitis may live longer after treatment with direct-acting antiviral agents (DAAs), but their risk of extrahepatic causes of death may rise as a result, according to investigators.

Importantly, this increasing rate of extrahepatic mortality shouldn’t be seen as a causal link with DAA use, cautioned lead author Donghee Kim, MD, PhD, of Stanford (Calif.) University, and colleagues. Instead, the upward trend is more likely because of successful treatment with DAAs, which can increase lifespan, and with it, time for susceptibility to extrahepatic conditions.

This was just one finding from a retrospective study that used U.S. Census and National Center for Health Statistics mortality records to evaluate almost 28 million deaths that occurred between 2007 and 2017. The investigators looked for mortality trends among patients with common chronic liver diseases, including viral hepatitis, alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD), noting that each of these conditions is associated with extrahepatic complications. The study included deaths due to extrahepatic cancer, cardiovascular disease, and diabetes.

While the efficacy of therapy for viral hepatitis has improved markedly since 2014, treatments for ALD and NAFLD have remained static, the investigators noted.

“Unfortunately, there have been no significant breakthroughs in the treatment of [ALD] over the last 2 decades, resulting in an increase in estimated global mortality to 3.8%,” the investigators wrote in Gastroenterology.

“[NAFLD] is the most common chronic liver disease in the world,” they added. “The leading cause of death in individuals with NAFLD is cardiovascular disease, followed by extrahepatic malignancies, and then liver-related mortality. However, recent trends in ALD and NAFLD-related extrahepatic complications in comparison to viral hepatitis have not been studied.”

The results of the current study supported the positive impact of DAAs, which began to see widespread use in 2014. Age-standardized mortality among patients with hepatitis C virus rose until 2014 (2.2% per year) and dropped thereafter (–6.5% per year). Mortality among those with hepatitis B virus steadily decreased over the study period (–1.2% per year).

Of note, while deaths because of HCV-related liver disease dropped from 2014 to 2017, extrahepatic causes of death didn’t follow suit. Age-standardized mortality for cardiovascular disease and diabetes increased at average annual rates of 1.9% and 3.3%, respectively, while the rate of extrahepatic cancer-related deaths held steady.

“The widespread use, higher efficacy and durable response to DAA agents in individuals with HCV infection may have resulted in a paradigm shift in the clinical progression of coexisting disease entities following response to DAA agents in the virus-free environment,” the investigators wrote. “These findings suggest assessment and identification of risk and risk factors for extrahepatic cancer, cardiovascular disease, and diabetes in individuals who have been successfully treated and cured of HCV infection.”

In sharp contrast with the viral hepatitis findings, mortality rates among patients with ALD and NAFLD increased at an accelerating rate over the 11-year study period.

Among patients with ALD, all-cause mortality increased by an average of 3.4% per year, at a higher rate in the second half of the study than the first (4.6% vs 2.1%). Liver disease–related mortality rose at a similar, accelerating rate. In the same group, deaths due to cardiovascular disease increased at an average annual rate of 2.1%, which was accelerating, while extrahepatic cancer-related deaths increased at a more constant rate of 3.6%.

For patients with NAFLD, all-cause mortality increased by 8.1% per year, accelerating from 6.1% in the first half of the study to 11.2% in the second. Deaths from liver disease increased at an average rate of 12.6% per year, while extrahepatic deaths increased significantly for all three included types: cardiovascular disease (2.0%), extrahepatic cancer (15.1%), and diabetes (9.7%).

Concerning the worsening rates of mortality among patients with ALD and NAFLD, the investigators cited a lack of progress in treatments, and suggested that “the quest for newer therapies must remain the cornerstone in our efforts.”

The investigators reported no external funding or conflicts of interest.

SOURCE: Kim D et al. Gastroenterology. 2019 Jun 25. doi: 10.1053/j.gastro.2019.06.026.

For non–status 1 patients with cirrhosis who are awaiting liver transplantation, type of renal dysfunction may be a key determinant of mortality risk, based on a retrospective analysis of more than 22,000 patients.

Risk of death was greatest for patients with acute on chronic kidney disease (AKI on CKD), followed by AKI alone, then CKD alone, reported lead author Giuseppe Cullaro, MD, of the University of California, San Francisco, and colleagues.

Although it is well known that renal dysfunction worsens outcomes among patients with liver cirrhosis, the impact of different types of kidney pathology on mortality risk has been minimally researched, the investigators wrote in Clinical Gastroenterology and Hepatology. “To date, studies evaluating the impact of renal dysfunction on prognosis in patients with cirrhosis have mostly focused on AKI.”

To learn more, the investigators performed a retrospective study involving acute, chronic, and acute on chronic kidney disease among patients with cirrhosis. They included data from 22,680 non–status 1 adults who were awaiting liver transplantation between 2007 and 2014, with at least 90 days on the wait list. Information was gathered from the Organ Procurement and Transplantation Network registry.

AKI was defined by fewer than 72 days of hemodialysis, or an increase in creatinine of at least 0.3 mg/dL or at least 50% in the last 7 days. CKD was identified by more than 72 days of hemodialysis, or an estimated glomerular filtration rate less than 60 mL/min/1.73 m² for 90 days with a final rate of at least 30 mL/min/1.73 m². Using these criteria, the researchers put patients into four possible categories: AKI on CKD, AKI, CKD, or normal renal function. The primary outcome was wait list mortality, which was defined as death, or removal from the wait list for illness. Follow-up started at the time of addition to the wait list and continued until transplant, removal from the wait list, or death.

Multivariate analysis, which accounted for final MELD-Na score and other confounders, showed that patients with AKI on CKD fared worst, with a 2.86-fold higher mortality risk (subhazard [SHR] ratio, 2.86) than that of patients with normal renal function. The mortality risk for acute on chronic kidney disease was followed closely by patients with AKI alone (SHR, 2.42), and more distantly by patients with CKD alone (SHR, 1.56). Further analysis showed that the disparity between mortality risks of each subgroup became more pronounced with increased MELD-Na score. In addition, evaluation of receiver operating characteristic curves for 6-month wait list mortality showed that the addition of renal function to MELD-Na score increased the accuracy of prognosis from an area under the curve of 0.71 to 0.80 (P less than .001).

“This suggests that incorporating the pattern of renal function could provide an opportunity to better prognosticate risk of mortality in the patients with cirrhosis who are the sickest,” the investigators concluded.

They also speculated about why outcomes may vary by type of kidney dysfunction.

“We suspect that those patients who experience AKI and AKI on CKD in our cohort likely had a triggering event – infection, bleeding, hypovolemia – that put these patients at greater risk for waitlist mortality,” the investigators wrote. “These events inherently carry more risk than stable nonliver-related elevations in serum creatinine that are seen in patients with CKD. Because of this heterogeneity of etiology in renal dysfunction in patients with cirrhosis, it is perhaps not surprising that unique renal function patterns variably impact mortality.”

The investigators noted that the findings from the study have “important implications for clinical practice,” and suggested that including type of renal dysfunction would have the most significant affect on accuracy of prognoses among patients at greatest risk of mortality.

The study was funded by a Paul B. Beeson Career Development Award and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Verna disclosed relationships with Salix, Merck, and Gilead.

SOURCE: Cullaro et al. Clin Gastroenterol Hepatol. 2019 Feb 1. doi: 10.1016/j.cgh.2019.01.043.

For non–status 1 patients with cirrhosis who are awaiting liver transplantation, type of renal dysfunction may be a key determinant of mortality risk, based on a retrospective analysis of more than 22,000 patients.

Risk of death was greatest for patients with acute on chronic kidney disease (AKI on CKD), followed by AKI alone, then CKD alone, reported lead author Giuseppe Cullaro, MD, of the University of California, San Francisco, and colleagues.

Although it is well known that renal dysfunction worsens outcomes among patients with liver cirrhosis, the impact of different types of kidney pathology on mortality risk has been minimally researched, the investigators wrote in Clinical Gastroenterology and Hepatology. “To date, studies evaluating the impact of renal dysfunction on prognosis in patients with cirrhosis have mostly focused on AKI.”

To learn more, the investigators performed a retrospective study involving acute, chronic, and acute on chronic kidney disease among patients with cirrhosis. They included data from 22,680 non–status 1 adults who were awaiting liver transplantation between 2007 and 2014, with at least 90 days on the wait list. Information was gathered from the Organ Procurement and Transplantation Network registry.

AKI was defined by fewer than 72 days of hemodialysis, or an increase in creatinine of at least 0.3 mg/dL or at least 50% in the last 7 days. CKD was identified by more than 72 days of hemodialysis, or an estimated glomerular filtration rate less than 60 mL/min/1.73 m² for 90 days with a final rate of at least 30 mL/min/1.73 m². Using these criteria, the researchers put patients into four possible categories: AKI on CKD, AKI, CKD, or normal renal function. The primary outcome was wait list mortality, which was defined as death, or removal from the wait list for illness. Follow-up started at the time of addition to the wait list and continued until transplant, removal from the wait list, or death.

Multivariate analysis, which accounted for final MELD-Na score and other confounders, showed that patients with AKI on CKD fared worst, with a 2.86-fold higher mortality risk (subhazard [SHR] ratio, 2.86) than that of patients with normal renal function. The mortality risk for acute on chronic kidney disease was followed closely by patients with AKI alone (SHR, 2.42), and more distantly by patients with CKD alone (SHR, 1.56). Further analysis showed that the disparity between mortality risks of each subgroup became more pronounced with increased MELD-Na score. In addition, evaluation of receiver operating characteristic curves for 6-month wait list mortality showed that the addition of renal function to MELD-Na score increased the accuracy of prognosis from an area under the curve of 0.71 to 0.80 (P less than .001).

“This suggests that incorporating the pattern of renal function could provide an opportunity to better prognosticate risk of mortality in the patients with cirrhosis who are the sickest,” the investigators concluded.

They also speculated about why outcomes may vary by type of kidney dysfunction.

“We suspect that those patients who experience AKI and AKI on CKD in our cohort likely had a triggering event – infection, bleeding, hypovolemia – that put these patients at greater risk for waitlist mortality,” the investigators wrote. “These events inherently carry more risk than stable nonliver-related elevations in serum creatinine that are seen in patients with CKD. Because of this heterogeneity of etiology in renal dysfunction in patients with cirrhosis, it is perhaps not surprising that unique renal function patterns variably impact mortality.”

The investigators noted that the findings from the study have “important implications for clinical practice,” and suggested that including type of renal dysfunction would have the most significant affect on accuracy of prognoses among patients at greatest risk of mortality.

The study was funded by a Paul B. Beeson Career Development Award and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Verna disclosed relationships with Salix, Merck, and Gilead.

SOURCE: Cullaro et al. Clin Gastroenterol Hepatol. 2019 Feb 1. doi: 10.1016/j.cgh.2019.01.043.

For non–status 1 patients with cirrhosis who are awaiting liver transplantation, type of renal dysfunction may be a key determinant of mortality risk, based on a retrospective analysis of more than 22,000 patients.

Risk of death was greatest for patients with acute on chronic kidney disease (AKI on CKD), followed by AKI alone, then CKD alone, reported lead author Giuseppe Cullaro, MD, of the University of California, San Francisco, and colleagues.

Although it is well known that renal dysfunction worsens outcomes among patients with liver cirrhosis, the impact of different types of kidney pathology on mortality risk has been minimally researched, the investigators wrote in Clinical Gastroenterology and Hepatology. “To date, studies evaluating the impact of renal dysfunction on prognosis in patients with cirrhosis have mostly focused on AKI.”

To learn more, the investigators performed a retrospective study involving acute, chronic, and acute on chronic kidney disease among patients with cirrhosis. They included data from 22,680 non–status 1 adults who were awaiting liver transplantation between 2007 and 2014, with at least 90 days on the wait list. Information was gathered from the Organ Procurement and Transplantation Network registry.

AKI was defined by fewer than 72 days of hemodialysis, or an increase in creatinine of at least 0.3 mg/dL or at least 50% in the last 7 days. CKD was identified by more than 72 days of hemodialysis, or an estimated glomerular filtration rate less than 60 mL/min/1.73 m² for 90 days with a final rate of at least 30 mL/min/1.73 m². Using these criteria, the researchers put patients into four possible categories: AKI on CKD, AKI, CKD, or normal renal function. The primary outcome was wait list mortality, which was defined as death, or removal from the wait list for illness. Follow-up started at the time of addition to the wait list and continued until transplant, removal from the wait list, or death.

Multivariate analysis, which accounted for final MELD-Na score and other confounders, showed that patients with AKI on CKD fared worst, with a 2.86-fold higher mortality risk (subhazard [SHR] ratio, 2.86) than that of patients with normal renal function. The mortality risk for acute on chronic kidney disease was followed closely by patients with AKI alone (SHR, 2.42), and more distantly by patients with CKD alone (SHR, 1.56). Further analysis showed that the disparity between mortality risks of each subgroup became more pronounced with increased MELD-Na score. In addition, evaluation of receiver operating characteristic curves for 6-month wait list mortality showed that the addition of renal function to MELD-Na score increased the accuracy of prognosis from an area under the curve of 0.71 to 0.80 (P less than .001).

“This suggests that incorporating the pattern of renal function could provide an opportunity to better prognosticate risk of mortality in the patients with cirrhosis who are the sickest,” the investigators concluded.

They also speculated about why outcomes may vary by type of kidney dysfunction.

“We suspect that those patients who experience AKI and AKI on CKD in our cohort likely had a triggering event – infection, bleeding, hypovolemia – that put these patients at greater risk for waitlist mortality,” the investigators wrote. “These events inherently carry more risk than stable nonliver-related elevations in serum creatinine that are seen in patients with CKD. Because of this heterogeneity of etiology in renal dysfunction in patients with cirrhosis, it is perhaps not surprising that unique renal function patterns variably impact mortality.”

The investigators noted that the findings from the study have “important implications for clinical practice,” and suggested that including type of renal dysfunction would have the most significant affect on accuracy of prognoses among patients at greatest risk of mortality.

The study was funded by a Paul B. Beeson Career Development Award and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Verna disclosed relationships with Salix, Merck, and Gilead.

SOURCE: Cullaro et al. Clin Gastroenterol Hepatol. 2019 Feb 1. doi: 10.1016/j.cgh.2019.01.043.

The Food and Drug Administration has warned that certain hepatitis C virus medications have led to rare instances of worsening liver function or liver failure.

Many of the affected patients had signs or symptoms of moderate to severe liver impairment (Child-Pugh class B or C), and given that these medications – glecaprevir/pibrentasvir (Mavyret), elbasvir/grazoprevir (Zepatier), and sofosbuvir/velpatasvir/voxilaprevir (Vosevi) – are not indicated for such patients, they should not have been prescribed in the first place, the FDA noted in the drug safety communication. Some cases had other preexisting risk factors, such as liver cancer, alcohol abuse, or serious medical illnesses associated with liver problems.

In most cases, impairment or decompensation occurred within the first 4 weeks of starting treatment, and symptoms resolved or new-onset worsening of liver function improved after stopping. These medicines have been widely used and, among patients with no or mild liver impairment, have been shown to be safe and effective.

Health care professionals should continue prescribing these medicines as indicated; they should assess patients at baseline for severity of liver disease and other risk factors and closely monitor these patients after for signs and symptoms of worsening liver function. Patients should be aware that the risk of injury is rare and continue taking prescribed medicines; if they develop fatigue, weakness, loss of appetite, nausea and vomiting, yellow eyes or skin, or light-colored stools, they should talk with their health care professional but should continue taking the medications in question until instructed to do otherwise.

The full communication is available on the FDA website and includes more facts about these drugs and information for patients and health care professionals.

[email protected]

The Food and Drug Administration has warned that certain hepatitis C virus medications have led to rare instances of worsening liver function or liver failure.

Many of the affected patients had signs or symptoms of moderate to severe liver impairment (Child-Pugh class B or C), and given that these medications – glecaprevir/pibrentasvir (Mavyret), elbasvir/grazoprevir (Zepatier), and sofosbuvir/velpatasvir/voxilaprevir (Vosevi) – are not indicated for such patients, they should not have been prescribed in the first place, the FDA noted in the drug safety communication. Some cases had other preexisting risk factors, such as liver cancer, alcohol abuse, or serious medical illnesses associated with liver problems.

In most cases, impairment or decompensation occurred within the first 4 weeks of starting treatment, and symptoms resolved or new-onset worsening of liver function improved after stopping. These medicines have been widely used and, among patients with no or mild liver impairment, have been shown to be safe and effective.

Health care professionals should continue prescribing these medicines as indicated; they should assess patients at baseline for severity of liver disease and other risk factors and closely monitor these patients after for signs and symptoms of worsening liver function. Patients should be aware that the risk of injury is rare and continue taking prescribed medicines; if they develop fatigue, weakness, loss of appetite, nausea and vomiting, yellow eyes or skin, or light-colored stools, they should talk with their health care professional but should continue taking the medications in question until instructed to do otherwise.

The full communication is available on the FDA website and includes more facts about these drugs and information for patients and health care professionals.

[email protected]

The Food and Drug Administration has warned that certain hepatitis C virus medications have led to rare instances of worsening liver function or liver failure.

Many of the affected patients had signs or symptoms of moderate to severe liver impairment (Child-Pugh class B or C), and given that these medications – glecaprevir/pibrentasvir (Mavyret), elbasvir/grazoprevir (Zepatier), and sofosbuvir/velpatasvir/voxilaprevir (Vosevi) – are not indicated for such patients, they should not have been prescribed in the first place, the FDA noted in the drug safety communication. Some cases had other preexisting risk factors, such as liver cancer, alcohol abuse, or serious medical illnesses associated with liver problems.

In most cases, impairment or decompensation occurred within the first 4 weeks of starting treatment, and symptoms resolved or new-onset worsening of liver function improved after stopping. These medicines have been widely used and, among patients with no or mild liver impairment, have been shown to be safe and effective.

Health care professionals should continue prescribing these medicines as indicated; they should assess patients at baseline for severity of liver disease and other risk factors and closely monitor these patients after for signs and symptoms of worsening liver function. Patients should be aware that the risk of injury is rare and continue taking prescribed medicines; if they develop fatigue, weakness, loss of appetite, nausea and vomiting, yellow eyes or skin, or light-colored stools, they should talk with their health care professional but should continue taking the medications in question until instructed to do otherwise.

The full communication is available on the FDA website and includes more facts about these drugs and information for patients and health care professionals.

[email protected]

The U.S. Preventive Services Task Force has issued a draft recommendation statement for screening for hepatitis C virus (HCV) infection in adolescents and adults, and now suggests that all adults aged 18-79 years receive screening.

Wikimedia Commons/BruceBlaus

This proposal represents an update and expansion of its current recommendation for screening for HCV infection. The draft recommendation incorporates new evidence and would replace the recommendation made in 2013, which calls for screening in persons at high risk for infection and one-time screening in adults born between 1945 and 1965 (Grade B).

“Today, more people are infected with hepatitis C than there were a decade ago, but there are now better treatments available. The evidence now shows more people can benefit from screening; therefore, we are recommending to screen all adults ages 18-79 for hepatitis C,” task force chair Douglas K. Owens, MD, MS, said in a bulletin issued by the USPSTF.

To update the previous recommendation, the USPSTF conducted a systematic review that included a total of 97 studies. No direct evidence was found regarding the benefits of HCV screening versus no screening or repeat versus one-time screening, and no new studies analyzed the psychological and social consequences of HCV screening.

Evidence concerning direct-acting antiviral (DAA) treatment was more compelling given that 49 trials found DAA therapy to be associated with pooled sustained virologic response (SVR) rates between 95.5% and 98.9% across genotypes. The rate of serious adverse events caused by DAA treatment was 1.9%, and the discontinuation of treatment because of adverse events was 0.4%. In seven trials involving adolescents, SVR rates after antiviral treatment were similar to those in adults.

Achieving an SVR after DAA treatment was associated with a decreased risk in those treated of all-cause mortality (hazard ratio, 0.40; 95% confidence interval, 0.28-0.56), liver mortality (HR, 0.11; 95% CI, 0.04-0.27), cirrhosis (HR, 0.36; 95% CI, 0.33-0.40), and hepatocellular carcinoma (HR, 0.29; 95% CI, 0.23-0.38), compared with those who did not respond.

Because of the evidence collected, the USPSTF issued a B recommendation for HCV screening in adults and recommended screening for all people aged 18-79 years in the draft recommendation statement. “Clinicians may want to consider screening in adolescents younger than age 18 years and in adults older than age 79 years who are at high risk [for HCV],” the proposal says.

The draft recommendation statement and evidence review is available at www.uspreventiveservicestaskforce.org. The public comment period will last until Sept. 23, 2019.

Help educate your patients about hepatitis C, their risks and treatment options using AGA patient education, which can be found in the GI Patient Center at https://www.gastro.org/practice-guidance/gi-patient-center/topic/hepatitis-c-hcv.

[email protected]

The U.S. Preventive Services Task Force has issued a draft recommendation statement for screening for hepatitis C virus (HCV) infection in adolescents and adults, and now suggests that all adults aged 18-79 years receive screening.

Wikimedia Commons/BruceBlaus

This proposal represents an update and expansion of its current recommendation for screening for HCV infection. The draft recommendation incorporates new evidence and would replace the recommendation made in 2013, which calls for screening in persons at high risk for infection and one-time screening in adults born between 1945 and 1965 (Grade B).

“Today, more people are infected with hepatitis C than there were a decade ago, but there are now better treatments available. The evidence now shows more people can benefit from screening; therefore, we are recommending to screen all adults ages 18-79 for hepatitis C,” task force chair Douglas K. Owens, MD, MS, said in a bulletin issued by the USPSTF.

To update the previous recommendation, the USPSTF conducted a systematic review that included a total of 97 studies. No direct evidence was found regarding the benefits of HCV screening versus no screening or repeat versus one-time screening, and no new studies analyzed the psychological and social consequences of HCV screening.

Evidence concerning direct-acting antiviral (DAA) treatment was more compelling given that 49 trials found DAA therapy to be associated with pooled sustained virologic response (SVR) rates between 95.5% and 98.9% across genotypes. The rate of serious adverse events caused by DAA treatment was 1.9%, and the discontinuation of treatment because of adverse events was 0.4%. In seven trials involving adolescents, SVR rates after antiviral treatment were similar to those in adults.

Achieving an SVR after DAA treatment was associated with a decreased risk in those treated of all-cause mortality (hazard ratio, 0.40; 95% confidence interval, 0.28-0.56), liver mortality (HR, 0.11; 95% CI, 0.04-0.27), cirrhosis (HR, 0.36; 95% CI, 0.33-0.40), and hepatocellular carcinoma (HR, 0.29; 95% CI, 0.23-0.38), compared with those who did not respond.

Because of the evidence collected, the USPSTF issued a B recommendation for HCV screening in adults and recommended screening for all people aged 18-79 years in the draft recommendation statement. “Clinicians may want to consider screening in adolescents younger than age 18 years and in adults older than age 79 years who are at high risk [for HCV],” the proposal says.

The draft recommendation statement and evidence review is available at www.uspreventiveservicestaskforce.org. The public comment period will last until Sept. 23, 2019.

Help educate your patients about hepatitis C, their risks and treatment options using AGA patient education, which can be found in the GI Patient Center at https://www.gastro.org/practice-guidance/gi-patient-center/topic/hepatitis-c-hcv.

[email protected]

The U.S. Preventive Services Task Force has issued a draft recommendation statement for screening for hepatitis C virus (HCV) infection in adolescents and adults, and now suggests that all adults aged 18-79 years receive screening.

Wikimedia Commons/BruceBlaus

This proposal represents an update and expansion of its current recommendation for screening for HCV infection. The draft recommendation incorporates new evidence and would replace the recommendation made in 2013, which calls for screening in persons at high risk for infection and one-time screening in adults born between 1945 and 1965 (Grade B).

“Today, more people are infected with hepatitis C than there were a decade ago, but there are now better treatments available. The evidence now shows more people can benefit from screening; therefore, we are recommending to screen all adults ages 18-79 for hepatitis C,” task force chair Douglas K. Owens, MD, MS, said in a bulletin issued by the USPSTF.

To update the previous recommendation, the USPSTF conducted a systematic review that included a total of 97 studies. No direct evidence was found regarding the benefits of HCV screening versus no screening or repeat versus one-time screening, and no new studies analyzed the psychological and social consequences of HCV screening.

Evidence concerning direct-acting antiviral (DAA) treatment was more compelling given that 49 trials found DAA therapy to be associated with pooled sustained virologic response (SVR) rates between 95.5% and 98.9% across genotypes. The rate of serious adverse events caused by DAA treatment was 1.9%, and the discontinuation of treatment because of adverse events was 0.4%. In seven trials involving adolescents, SVR rates after antiviral treatment were similar to those in adults.

Achieving an SVR after DAA treatment was associated with a decreased risk in those treated of all-cause mortality (hazard ratio, 0.40; 95% confidence interval, 0.28-0.56), liver mortality (HR, 0.11; 95% CI, 0.04-0.27), cirrhosis (HR, 0.36; 95% CI, 0.33-0.40), and hepatocellular carcinoma (HR, 0.29; 95% CI, 0.23-0.38), compared with those who did not respond.

Because of the evidence collected, the USPSTF issued a B recommendation for HCV screening in adults and recommended screening for all people aged 18-79 years in the draft recommendation statement. “Clinicians may want to consider screening in adolescents younger than age 18 years and in adults older than age 79 years who are at high risk [for HCV],” the proposal says.

The draft recommendation statement and evidence review is available at www.uspreventiveservicestaskforce.org. The public comment period will last until Sept. 23, 2019.

Help educate your patients about hepatitis C, their risks and treatment options using AGA patient education, which can be found in the GI Patient Center at https://www.gastro.org/practice-guidance/gi-patient-center/topic/hepatitis-c-hcv.

[email protected]

Use of nonselective beta-blockers to reduce portal pressure in cirrhosis improved outcomes in adults with or without ascites, based on data from a meta-analysis of more than 1,000 patients.

Wikimedia Commons/Cancer Research UK

Previous research has suggested that nonselective beta-blockers (NSBBs) might have a negative effect on patients with refractory ascites, but the effect on patients with and without ascites has not been assessed, wrote Laura Turco, MD, of the University of Modena and Reggio Emilia, Emilia-Romagna, Italy, and colleagues.

In a study published in Clinical Gastroenterology and Hepatology, the researchers analyzed 1,113 cirrhosis patients including 452 with ascites. Overall, 968 patients had received treatment with NSBBs. Response to pressure reduction was defined as a decrease of more than 20% from baseline or a decrease to less than 12 mm Hg.

A total of 329 of the 661 patients without ascites (50%) met the definition as responders. These responders had significantly lower odds than did nonresponders of a combination of clinical events including ascites, variceal hemorrhage, or encephalopathy (odds ratio, 0.35) and also had significantly lower odds than nonresponders of liver transplantation or death (OR, 0.50).

A total of 188 of the 452 patients with ascites were responders (42%). These responders had significantly lower odds than those of nonresponders (OR, 0.27) of variceal hemorrhage, refractory ascites, spontaneous bacterial peritonitis, or hepatorenal syndrome. The responders also had significantly lower odds of liver transplantation or death (OR, 0.47).

The results are important in light of concerns about the impact of NSBBs on renal function and mortality in cirrhosis patients with ascites, the researchers said.

The study findings were limited by several factors, including the use of retrospective data from prospective studies, and the incomplete collection of data on the variables of comorbidities, hepatocellular carcinoma, and other predictive scores; alcohol use or abstinence was a potential confounder as well, the researchers noted.

However, “By showing that reductions in portal pressure induced by NSBB-based pharmacologic therapy improve outcomes and decrease mortality, our study supports the use of NSBB in all clinical settings (primary or secondary prophylaxis) and in both patients with or without ascites,” they concluded. They found no heterogeneity among the studies included in the analysis.

The study was supported by multiple sources including the University of Modena and Reggio Emilia, Yale Liver Center, National Institutes of Health, and Instituto de Salud Carlos III, and was cofunded by the European Union. The researchers had no financial conflicts to disclose.

SOURCE: Turco L et al. Clin Gastroenterol Hepatol. 2019 June 5. doi: 10.1016/j.cgh.2019.05.050.

Use of nonselective beta-blockers to reduce portal pressure in cirrhosis improved outcomes in adults with or without ascites, based on data from a meta-analysis of more than 1,000 patients.

Wikimedia Commons/Cancer Research UK

Previous research has suggested that nonselective beta-blockers (NSBBs) might have a negative effect on patients with refractory ascites, but the effect on patients with and without ascites has not been assessed, wrote Laura Turco, MD, of the University of Modena and Reggio Emilia, Emilia-Romagna, Italy, and colleagues.

In a study published in Clinical Gastroenterology and Hepatology, the researchers analyzed 1,113 cirrhosis patients including 452 with ascites. Overall, 968 patients had received treatment with NSBBs. Response to pressure reduction was defined as a decrease of more than 20% from baseline or a decrease to less than 12 mm Hg.

A total of 329 of the 661 patients without ascites (50%) met the definition as responders. These responders had significantly lower odds than did nonresponders of a combination of clinical events including ascites, variceal hemorrhage, or encephalopathy (odds ratio, 0.35) and also had significantly lower odds than nonresponders of liver transplantation or death (OR, 0.50).

A total of 188 of the 452 patients with ascites were responders (42%). These responders had significantly lower odds than those of nonresponders (OR, 0.27) of variceal hemorrhage, refractory ascites, spontaneous bacterial peritonitis, or hepatorenal syndrome. The responders also had significantly lower odds of liver transplantation or death (OR, 0.47).

The results are important in light of concerns about the impact of NSBBs on renal function and mortality in cirrhosis patients with ascites, the researchers said.

The study findings were limited by several factors, including the use of retrospective data from prospective studies, and the incomplete collection of data on the variables of comorbidities, hepatocellular carcinoma, and other predictive scores; alcohol use or abstinence was a potential confounder as well, the researchers noted.

However, “By showing that reductions in portal pressure induced by NSBB-based pharmacologic therapy improve outcomes and decrease mortality, our study supports the use of NSBB in all clinical settings (primary or secondary prophylaxis) and in both patients with or without ascites,” they concluded. They found no heterogeneity among the studies included in the analysis.

The study was supported by multiple sources including the University of Modena and Reggio Emilia, Yale Liver Center, National Institutes of Health, and Instituto de Salud Carlos III, and was cofunded by the European Union. The researchers had no financial conflicts to disclose.

SOURCE: Turco L et al. Clin Gastroenterol Hepatol. 2019 June 5. doi: 10.1016/j.cgh.2019.05.050.

Use of nonselective beta-blockers to reduce portal pressure in cirrhosis improved outcomes in adults with or without ascites, based on data from a meta-analysis of more than 1,000 patients.

Wikimedia Commons/Cancer Research UK

Previous research has suggested that nonselective beta-blockers (NSBBs) might have a negative effect on patients with refractory ascites, but the effect on patients with and without ascites has not been assessed, wrote Laura Turco, MD, of the University of Modena and Reggio Emilia, Emilia-Romagna, Italy, and colleagues.

In a study published in Clinical Gastroenterology and Hepatology, the researchers analyzed 1,113 cirrhosis patients including 452 with ascites. Overall, 968 patients had received treatment with NSBBs. Response to pressure reduction was defined as a decrease of more than 20% from baseline or a decrease to less than 12 mm Hg.

A total of 329 of the 661 patients without ascites (50%) met the definition as responders. These responders had significantly lower odds than did nonresponders of a combination of clinical events including ascites, variceal hemorrhage, or encephalopathy (odds ratio, 0.35) and also had significantly lower odds than nonresponders of liver transplantation or death (OR, 0.50).

A total of 188 of the 452 patients with ascites were responders (42%). These responders had significantly lower odds than those of nonresponders (OR, 0.27) of variceal hemorrhage, refractory ascites, spontaneous bacterial peritonitis, or hepatorenal syndrome. The responders also had significantly lower odds of liver transplantation or death (OR, 0.47).

The results are important in light of concerns about the impact of NSBBs on renal function and mortality in cirrhosis patients with ascites, the researchers said.

The study findings were limited by several factors, including the use of retrospective data from prospective studies, and the incomplete collection of data on the variables of comorbidities, hepatocellular carcinoma, and other predictive scores; alcohol use or abstinence was a potential confounder as well, the researchers noted.

However, “By showing that reductions in portal pressure induced by NSBB-based pharmacologic therapy improve outcomes and decrease mortality, our study supports the use of NSBB in all clinical settings (primary or secondary prophylaxis) and in both patients with or without ascites,” they concluded. They found no heterogeneity among the studies included in the analysis.

The study was supported by multiple sources including the University of Modena and Reggio Emilia, Yale Liver Center, National Institutes of Health, and Instituto de Salud Carlos III, and was cofunded by the European Union. The researchers had no financial conflicts to disclose.

SOURCE: Turco L et al. Clin Gastroenterol Hepatol. 2019 June 5. doi: 10.1016/j.cgh.2019.05.050.