Long-Term Liver Morbidity and Mortality After Hepatitis C Virus Elimination by Direct-Acting Antivirals

Background and Aim: More accurate stratification of patients with chronic hepatitis C after permanent hepatitis C virus (HCV) clearance by direct-acting antivirals (DAAs) is important for improving long-term surveillance and treatment. The aim of this study was to stratify patients with chronic hepatitis C who are at risk of developing hepatocellular carcinoma (HCC) after HCV cure. Methods: This multicenter, retrospective cohort study included 3177 consecutive adult chronic hepatitis C patients without decompensated cirrhosis who were treated with all-oral DAAs. The primary study endpoints were long-term cumulative de novo HCC incidence, HCC recurrence rates, and survival. Additionally, we analyzed the development of HCC by patients without cirrhosis, stratified by age and fibrosis status according to the FIB-4 index. Results: After exclusions, data from 3024 patients were available for analysis. The overall median follow-up period was 6.5 years. None of the patients with non-cirrhosis/FIB-4 < 1.45 (n = 475) developed HCC regardless of background factors. For patients with non-cirrhosis/FIB-4 >= 3.25, older age had a greater impact on HCC incidence (log-rank test: p = 0.038). In addition, metabolic factors, including body mass index and diabetes mellitus, were not related to HCC incidence. HCC recurrence commonly occurred within 5 years after HCV cure; nevertheless, HCV cure contributed to an improvement of survival rates. Conclusions: Age is a pivotal factor in predicting de novo HCC development following HCV cure in patients with moderate to advanced fibrosis. Conversely, patients with mild fibrosis (FIB-4 < 1.45) may be eligible for discharge from specialized care after achieving HCV elimination.