Clinical outcomes following DAA therapy in patients with HCV-related cirrhosis depend on disease severity

Background & Aims: HCV-infected patients with cirrhosis achieve high sustained virological response (SVR) rates with direct-acting antivirals (DAAs) even after hepatic decompensation. We aimed to assess the clinical outcome following DAAs among patients with compensated and decompensated cirrhosis in relation to SVR and changes in model for end-stage liver disease (MELD) score. Methods: Consecutive DAA-treated chronic HCV-infected patients with cirrhosis from 4 hepatology clinics were included. The primary endpoint in survival analyses was clinical disease progression, defined as liver failure, hepatocellular carcinoma, liver transplantation or death. Results: In total, 868 patients were included with a median age of 59 (IQR 54–65) years; 719 (83%) with Child-Pugh A cirrhosis and 149 (17%) with Child-Pugh B/C cirrhosis. SVR was attained by 647 (90%) Child-Pugh A patients and 120 (81%) Child-Pugh B/C patients. During a median follow-up of 28 (IQR 20–36) months, 102 (14%) Child-Pugh A patients and 96 (64%) Child-Pugh B/C patients experienced clinical disease progression. SVR was independently associated with an improved event-free survival in patients with Child-Pugh A cirrhosis (adjusted hazard ratio [HR] 0.47; 95% CI 0.27–0.82, p = 0.007), but not in patients with Child-Pugh B/C cirrhosis (adjusted HR 1.23; 95% CI 0.67–2.26; p = 0.51). Twelve weeks post-DAAs, 28 (19%) patients with Child-Pugh B/C cirrhosis had ≥2-point MELD decline, but their 2-year event-free survival did not differ from those with a stable MELD (47.9%; 95% CI 28.7–67.1 vs. 48.9%; 95% CI 38.1–59.7, respectively, p = 0.99). Conclusions: Among patients with chronic HCV infection, DAA-induced SVR was associated with a reduced risk of clinical disease progression in patients with Child-Pugh A cirrhosis but not in patients with Child-Pugh B/C cirrhosis. In Child-Pugh B/C cirrhosis, a ≥2-point MELD decline did not translate into improved clinical outcome. Lay summary: Chronic HCV infection can be cured with antiviral therapy. In this study, we evaluated the long-term effects of antiviral therapy on liver-related complications in patients with cirrhosis. Our results suggest that patients with compensated cirrhosis who were cured of their HCV infection have a lower rate of complications. In contrast, the rate of complications was not related to virological cure among those with decompensated cirrhosis. While these patients seem to remain in need of liver transplantation, antiviral therapy may lower their priority on the liver transplantation waiting list

Progression of the FIB-4 index among patients with chronic HCV infection and early liver disease

Background and aims Historical paired liver biopsy studies are likely to underestimate current progression of disease in patients with chronic hepatitis C virus (HCV) infection. We aimed to assess liver disease progression according to the non-invasive Fibrosis-4 (FIB-4) index in patients with chronic HCV and early disease.Methods and results Patients diagnosed with chronic HCV and FIB-4 <3.25 from four international liver clinics were included in a retrospective cohort study. Follow-up ended at start of antiviral therapy resulting in sustained virological response, at time of liver transplantation or death. Primary outcome of advanced liver disease was defined as FIB-4 >3.25 during follow-up. Survival analyses were used to assess time to FIB-4 >3.25.In total, 4286 patients were followed for a median of 5.0 (IQR 1.7–9.4) years, during which 41 071 FIB-4 measurements were collected. At baseline, median age was 47 (IQR 39–55) years, 2529 (59.0%) were male, and 2787 (65.0%) patients had a FIB-4 <1.45. Advanced liver disease developed in 821 patients. Overall, 10-year cumulative incidence of advanced disease was 32.1% (95% CI 29.9% to 34.3%). Patients who developed advanced disease showed an exponential FIB-4 increase. Among patients with a presumed date of HCV infection, cumulative incidence of advanced disease increased 7.7-fold from 20 to 40 years as opposed to the first 20 years after HCV infection.Conclusions The rate of advanced liver disease is high among chronic HCV-infected patients with early disease at time of diagnosis, among whom liver disease progression accelerated over time. These results emphasise the need to overcome any limitations with respect to diagnosing and treating all patients with chronic HCV across the globe