Faculty Bibliography

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.

Abstract LBO-06 is under embargo until Saturday 13 April 2019, 07:00. This abstract has been selected to be highlighted during official EASL Press Office activities or in official EASL Press Office materials that will be made publicly available on the congress website at 07:00 (CET) on the day of their presentation at the congress. Industry must not issue press releases - even under embargo - covering the data contained in abstracts selected to be highlighted during official EASL Press Office activities or in official EASL Press Office materials until the individual embargo for each data set lifts. Media must not issue coverage of the data contained in abstracts selected to be highlighted during official EASL Press Office activities or in official EASL Press Office materials until the individual embargo for each data set lifts. Journalists, industry, investigators and/or study sponsors must abide by the embargo times set by EASL. Violation of the embargo will be taken seriously. Individuals and/or sponsors who violate EASL's embargo policy may face sanctions relating to current and future abstract submissions, presentations and visibility at EASL Congresses. The EASL Governing Board is at liberty to ban attendance and/or retract data. Copyright for abstracts (both oral and poster) on the website and as made available during The International CongressTM 2019
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Background and aims: Although improvement of PROs in CHC patients who achieve SVR with direct-acting antivirals (DAAs) has been demonstrated, PROs of CHC patients who failed to achieve SVR with new DAAs have not been documented. AIM: Compare post-treatment PRO scores between CHC patients who did and did not achieve SVR after DAA treatment.
Method(s): Patients who had completed treatment in a clinical trial were prospectively enrolled in two registries based on treatment outcomes: the SVR Registry and Non-SVR Registry. PRO scores were prospectively collected using the Short Form-36 (SF-36) every 12-24 weeks.
Result(s): There were 4, 234 patients with SVR and 242 without SVR who were enrolled in these two registries and had pre-treatment PRO data: 54 +/- 10 years old, 63% male, 83% white, 65% enrolled in the U.S., 17% with cirrhosis prior to treatment, 12% with coinfection with HIV, and 25% with history of depression. Upon registry enrollment, patients with SVR experienced significant improvement in all their PRO scores in comparison to their own pre-treatment baseline scores (all p < 0.0001) while there was no improvement in any PRO score (all one-sided p > 0.05) and, in fact, a significant decrement in General Health of SF-36 (mean -2.8 points, p = 0.008) in CHC patients without SVR. Furthermore, CHC patients without SVR experienced significant PRO decrements while followed on the registry (up to -7.0 points decrements in 4/8 SF-36 domains at registry week 12; up to -9.2 points in all 8 domains at week 24; up to -8.3 points in 5/8 domains at week 48, and up to -9.0 points in 4/8 domains at week 96 (all p < 0.05). In contrast, patients with SVR experienced sustained improvement of their PRO scores while on the registry (up to +7.0 points at registry week 24, up to +6.9 points at week 48, up to +6.1 points at week 96 (all p < 0.001) (Figure). In multivariate analysis, having achieved SVR was independently associated with superior scores in all SF-36 domains at all registry time points: beta from +4.8 to +14.9 points (all p <= 0.01). PRO scores were lower and their decrements were greater in cirrhotics without SVR than non-cirrhotic without SVR (p < 0.05).
Conclusion(s): These data clearly show the benefit of achieving SVR for patients' well-being which is contrasted to the deleterious impact of viremia (not achieving SVR). These data should inform payers and policy makers to remove any barriers to HCV treatment which could lead to the cure and reduce patients' suffering and PRO impairment. NAFLD: Diagnostics and non-invasive assessment
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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.

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.

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.

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

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.