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Background and aims: Patients with chronic hepatitis C (CHC)and cirrhosis have severe impairment of health-related quality of life (HRQL)and other patient-reported outcomes (PROs). Although achieving sustained virologic response (SVR)leads to improvement in PROs, the long-term sustainability of this improvement in patients with cirrhosis has not been well established. AIM: To assess long-term changes in PRO scores in patients with cirrhosis who have achieved SVR after treatment with a direct-acting antiviral. Method(s): Patients with HCV and cirrhosis who had been treated in 14 clinical trials and had achieved SVR-12 were prospectively enrolled in a long-term registry (#NCT02292706). PROs were collected every 24 weeks for 120 weeks using Short Form-36 (SF-36), Chronic Liver Disease Questionnaire (CLDQ)-HCV, and Work Productivity and Activity Impairment (WPAI)instruments which collectively return 20 PRO domain scores. Result(s): Data was available for 785 HCV cirrhotics with SVR-12: 659 compensated (CC)and 126 decompensated cirrhosis (DCC). Their pre-treatment characteristics include age 57.6 +/- 7.3 years, 69% male, 22% with type 2 diabetes, 50% employed. Prior to their initial treatment, DCC patients had severely impaired PRO scores in comparison to CC patients (by average 5.8% to 15.6% of a PRO range size; p < 0.05 for 15/20 PRO domain scores); the most pronounced difference between DCC and CC patients was in physical health- and activity-related domains. After achieving SVR and enrollment into the registry, significant PRO improvements from their pre-treatment scores were noted in 19/20 PRO domains in CC patients (ranging from average +2.2% to +17.0% of a PRO range size)and in 10/20 PRO domains in DCC patients (from +4.4% to +20.5% of a PRO score range)(all p < 0.05). These PRO gains persisted or continued to improve over time up to 120 weeks after entering the registry in patients with both CC and DCC (Figure). In DCC patients, the presence of hepatic encephalopathy was the most important contributor to PRO impairment (up to -10.2%, p < 0.01 for 12/20 PRO scores). [Table Presented]Conclusion: Achieving SVR leads to significant and sustainable improvement of PRO scores in patients with pre-treatment cirrhosis.

INTRODUCTION/BACKGROUND:Treatment options are limited for people infected with hepatitis C virus (HCV) with decompensated liver disease. The C-SALT study assessed elbasvir (EBR) plus grazoprevir (GZR) in individuals with HCV genotype 1 infection and Child-Pugh class B (CP-B) cirrhosis. METHODS:In this 12-week, phase 2, nonrandomized, open-label study (NCT02115321; Protocol MK-5172-059), participants with CP-B cirrhosis received EBR 50 mg plus GZR 50 mg once daily, and a control group of noncirrhotic participants received EBR 50 mg plus GZR 100 mg once daily. The primary endpoint was sustained virologic response 12 weeks after the end of therapy. RESULTS:Sustained virologic response at 12 weeks after the end of therapy was achieved by 27/30 (90.0%) CP-B participants and 10/10 (100.0%) noncirrhotic participants. Two participants relapsed, and one died during follow-up after having undetectable HCV RNA at the end of treatment. Most CP-B participants had stable or improved model for end-stage liver disease and Child-Pugh scores at follow-up week 12 compared with baseline. There was no significant difference in drug exposure between groups, despite the differing GZR dose. Adverse events occurring in >10% of participants were fatigue (CP-B: 30.0%; noncirrhotic: 30.0%), arthralgia (16.7%; 20.0%), nausea (10.0%; 20.0%), and headache (10.0%; 50.0%). No serious treatment-related adverse events or hepatic events of clinical interest occurred. CONCLUSIONS:EBR 50 mg plus GZR 50 mg once daily for 12 weeks was highly effective and well tolerated in a traditionally hard-to-treat population. TRANSLATIONAL IMPACT/UNASSIGNED:Although EBR plus reduced-dose GZR is not available for people with CP-B cirrhosis, these results complement phase 2/3 trial data and real-world experience with EBR/GZR.Open Access This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Background: Chronic hepatitis C (CHC) and non-alcoholic steatohepatitis (NASH) are both associated with impairment of healthrelated quality of life (HRQL). The most profound impairment is usually seen in patients with cirrhosis.
Aim(s): To compare HRQL scores in patients with cirrhosis due to CHC to NASH.
Method(s): Patients with CHC and NASH and compensated cirrhosis completed SF-36, CLDQ, and Work Productivity and Activity questionnaires while off-treatment.
Result(s): We included 1460 patients with NASH or CHC and cirrhosis: 57.4 +/- 8.2 years, 44% male, 40% history of psychiatric disorders, 50% employed (all p>0.05 between NASH and CHC). Cirrhotic patients with NASH had higher BMI (mean 33.8 vs. 28.2) and more type 2 diabetes (77% vs. 18%) (p<0.01). Patients with NASH had lower HRQL in Physical Functioning, Bodily Pain, General Health domains, and Physical Summary of SF-36 (by 3.6-4.4 points on a 0-100 scale, all p<0.01). Despite this, patients with CHC had lower Mental Health score of SF-36 (mean 69.5 vs. 73.0) and Emotional score of CLDQ (mean 4.9 vs. 5.3 on a 1-7 scale), and higher Activity Impairment score of WPAI (0.27 vs. 0.19) (all p<0.002). In multivariate regression analysis, after adjustment for demographic and clinical parameters, having NASH was independently associated with lower physical HRQL scores (beta - 3.6 to - 4.3 for SF-36 domains) and higher mental health-related scores (beta +3.8 for Mental Health of SF-36, +0.33 for Emotional of CLDQ) (all p<0.01).
Conclusion(s): Patients with NASH and cirrhosis have more impairment of their physical health-related scores than demographically similar patients with hepatitis C

European treatment guidelines for hepatitis C virus (HCV) infection recommend that people with genotype (GT) 1a infection and baseline viral load ≤800 000 IU/mL receive elbasvir/grazoprevir (EBR/GZR) for 12 weeks, and those with baseline viral load >800 000 IU/mL receive EBR/GZR plus ribavirin for 16 weeks. This analysis was conducted to clarify whether baseline viral load can serve as an accurate, sensitive or specific stratification factor for defining EBR/GZR regimens. In this post hoc, integrated analysis, participants with GT1a infection who received EBR 50 mg/GZR 100 mg for 12 weeks were stratified according to baseline viral load. Sustained virologic response at 12 weeks post-treatment was achieved by 95.2% (911/957) of participants and was higher among participants with baseline viral load ≤800 000 IU/mL vs >800 000 IU/mL (98.5% vs 93.9%). The 800 000 IU/mL threshold had a positive predictive value of 98.5%, a negative predictive value of 6.1%, a specificity of 91.3%, a sensitivity of 28.4% and an overall accuracy of 31.5%. A baseline viral load cutpoint of 800 000 IU/mL had high positive predictive value and specificity but poor negative predictive value, sensitivity and accuracy in predicting treatment outcomes in this population. Baseline NS5A resistance-associated substitutions (RASs) were detected in 25% (1/4) of virologic failures with baseline viral load ≤800 000 IU/mL and 59.5% (25/42) of those with baseline viral load >800 000 IU/mL. Overall, these data suggest that, compared with the use of a baseline viral load cutpoint, baseline testing for NS5A RASs enables more individuals to receive the 12-week EBR/GZR regimen without compromising the opportunity for SVR.

Primary biliary cholangitis (PBC) is a chronic, cholestatic, autoimmune disease with a variable progressive course. PBC can cause debilitating symptoms including fatigue and pruritus and, if left untreated, is associated with a high risk of cirrhosis and related complications, liver failure, and death. Recent changes to the PBC landscape include a name change, updated guidelines for diagnosis and treatment as well as new treatment options that have recently become available. Practicing clinicians face many unanswered questions when managing PBC. To assist these healthcare providers in managing patients with PBC, the American College of Gastroenterology (ACG) Institute for Clinical Research & Education, in collaboration with the Chronic Liver Disease Foundation (CLDF), organized a panel of experts to evaluate and summarize the most current and relevant peer-reviewed literature regarding PBC. This, combined with the extensive experience and clinical expertise of this expert panel, led to the formation of this clinical guidance on the diagnosis and management of PBC.

BACKGROUND:While hepatitis B and C have been the main drivers of hepatocellular carcinoma (HCC), non-alcoholic steatohepatitis (NASH) has recently become an important cause of HCC. The aim of this study was to assess the causes of HCC among liver transplant (LT) candidates in the U.S. METHODS:The Scientific Registry of Transplant Recipients (2002-2016) was used to estimate the trends in prevalence of HCC in LT candidates with the most common types of chronic liver disease: alcoholic liver disease (ALD), chronic hepatitis B (CHB), chronic hepatitis C, and NASH. RESULTS:158,347 adult LT candidates were included. Of these, 26,121 (16.5%) had HCC; this proportion increased from 6.4% (2002) to 23.0% (2016) (trend p<0.0001). Over the study period, CHC remained the most common etiology for HCC (65%). The proportions of HCC accounted for by CHC and ALD remained stable (both trend p>0.10), the proportion of CHB decreased 3.1-fold (p<0.0001), while the proportion of NASH in HCC increased 7.7-fold (from 2.1% to 16.2%, p<0.0001). Furthermore, since 2002, the prevalence of HCC in LT candidates with NASH increased 11.8-fold, while this rate increased 6.0-fold in CHB, 3.4-fold in ALD and 2.3-fold in CHC (all p<0.0001); the increasing trend in NASH was steeper than that for any other etiology (p<0.0001 in a trend regression model). The proportion of LT candidates with HCC who were ultimately transplanted or died while waiting did not differ between etiologies (p>0.05). CONCLUSIONS:Non-alcoholic steatohepatitis is the most rapidly growing cause of HCC among U.S. patients listed for liver transplantation.

Type 2 diabetes mellitus (T2DM) has been identified as an extrahepatic manifestation of chronic HCV infection. Conversely, in the context of chronic HCV infection, T2DM can accelerate the course of HCV-induced liver disease leading to increased risk of fibrosis, cirrhosis and hepatocellular carcinoma. The presence of T2DM negatively impacts the efficacy of interferon-based antiviral therapy, but real-world data with high-efficacy direct-acting antiviral therapies suggest high viral clearance rates in T2DM patients. In HCV-infected individuals, viral eradication is associated with a reduced risk of de novo T2DM in non-diabetic patients and beneficial metabolic changes in patients with T2DM, highlighting the importance of antiviral treatment and physician awareness of this association.

Background: NAFLD and AFLD are overlapping liver diseases in which both metabolic syndrome (MS) and alcohol consumption contribute to progressive liver disease. Aim: To assess the impact of alcohol consumption and MS on mortality of individuals with NAFLD and AFLD. Methods: National Health and Nutrition and Examination Survey III (1988-1994)-National Death Index linked files were used to select participants with at least mild hepatic steatosis on an ultrasound. All other causes of liver disease (HBV, HCV, iron overload) were excluded. Alcohol consumption was selfreported as mean number of drinks per day for 1 year prior to data collection. Using alcohol consumption data, study cohort was divided into 5 groups: no alcohol use, minimal (<=3 and <=1.5 drinks/week for men and women), moderate (>minimal but <=2 and <=1 drinks/day for men and women), substantial (>moderate but <=3 and <=1.5 drinks/day for men and women), and excessive (>3 and 1.5 drinks/day for men and women). Association of alcohol consumption with mortality was quantified using Cox proportional hazard model while accounting for the survey design. Results: The study cohort included 4,309 individuals with hepatic steatosis: mean age 46.0 years, 51% male, 76% white, 46% with MS (ATPIII Criteria). Of the study cohort, 55.8% reported no, 18.4%-minimal, 16.7%-moderate, 3.7%-substantial, and 5.4%-excessive alcohol use. After mean follow-up of 20 years, 23% of participants died. Individuals with steatosis who reported excessive alcohol consumption were more commonly male and smokers (both p<0.05). Despite similar age (p=0.69), they had significantly higher mortality rate in comparison to those with steatosis and non-excessive alcohol use (33.0% vs. 22.5%, p=0.001), especially after 5 years of follow-up. In multivariate analysis, presence of MS [adjusted hazard ratio (aHR)=1.38 (1.09-1.76)], older age [aHR=1.094 (1.080-1.108)], smoking [aHR=2.101 (1.628-2.710)] and male gender [aHR=1.315 (1.125-1.538)] were independently associated with an increased risk of mortality in individuals with hepatic steatosis. In addition, excessive alcohol consumption was independently associated with mortality after adjustment for confounders: aHR=1.61 (1.12-2.33), p=0.01; lower average amounts of alcohol consumption were not associated with mortality (all p>0.20). In a subgroup analysis, association of excessive alcohol use with mortality was significant in individuals with MS [aHR=2.45 (1.37-4.39)] but not without MS (p=0.86). Conclusion: Excessive alcohol consumption is associated with increased mortality in the presence of MS, suggesting an important overlap between NAFLD and AFLD