Incidence of liver and non-liver-related outcomes in patients with HCV-cirrhosis after SVR.

BACKGROUND AND AIM As the long-term benefits of a sustained virological response (SVR) in hepatitis C virus (HCV) cirrhosis following direct-acting antivirals (DAA) remain undefined, we assessed the incidence and predictors of liver-related events (LRE), non-liver related events (NLRE) and mortality in DAA-treated cirrhotics. METHODS Consecutive SVR cirrhotics were enrolled in a longitudinal, single-center study, and divided into 3 cohorts: Cohort A (CPT-A without previous LRE), Cohort B (CPT-B or CPT-A with prior non-HCC LRE), Cohort C (previous HCC). RESULTS 636 cirrhotics (65 years-old, 58% males, 89% CPT-A) were followed for 51 (8-68) months [Cohort A n=480, Cohort B n=89, Cohort C n=67]. The 5-year estimated cumulative incidences of LRE were 10.4% in Cohort A vs. 32.0% in Cohort B [HCC 7.7% vs. 19.7%; ascites 1.4% vs. 8.6%; variceal bleeding 1.3% vs. 7.8%; encephalopathy 0 vs. 2.5%] vs. 71% in Cohort C [HCC only] (p<0.0001). The corresponding figures for NLRE were 11.7% in Cohort A vs. 17.9% in Cohort B vs. 17.5% in Cohort C (p=0.32). The 5-year estimated probabilities of liver-related vs. non-liver related deaths were 0.5% vs. 4.5% in Cohort A, 16.2% vs. 8.8% in Cohort B and 12.1% vs. 7.7% in Cohort C. All-cause mortality rate in Cohort A was similar to the rate expected for the general population stratified by age, gender and calendar year according to the Human Mortality Database, while it was significantly higher in Cohort B. CONCLUSIONS Cirrhotic patients with an SVR to DAA face risks of liver-related and non-liver related events and mortality; however, their incidence is strongly influenced by pre-DAA patient history. LAY SUMMARY • In this large single-center study enrolling HCV cirrhotic patients cured by direct-acting antivirals, pre-treatment liver disease history strongly influenced long-term outcomes. • In HCV cirrhotic patients, hepatocellular carcinoma accounted for the most frequent liver-related complication after viral cure. • Due to improved long-term outcomes, cirrhotic patients after HCV cure are exposed to a significant proportion of non-liver related events and mortality.