Long Term Clinical Outcomes in Chronic Hepatitis C Patients Who Achieved SVR Following DAAs: A Decade Long Prospective Study

Abstract

The long-term impact of direct-acting antivirals (DAAs) in chronic hepatitis C virus (HCV) patients remains debated. This study evaluates all-cause mortality, hepatocellular carcinoma (HCC), and decompensated cirrhosis in DAAs-treated patients enrolled in the ‘Educate, Test, and Treat’ programme. This prospective observational study included HCV patients treated at the Egyptian Liver Research Institute and Hospital (ELRIAH) from 2015 to 2018. Participants were recruited from 12 villages and followed until the end of 2024. Exclusions included decompensated liver disease, hepatitis B virus (HBV)/human immunodeficiency virus (HIV) co-infection, prior HCC, or severe comorbidities. Follow-up included clinical, biochemical, ultrasound, and liver stiffness measurements (LSM). Primary outcomes were all-cause mortality, HCC, and decompensated cirrhosis. Kaplan–Meier curves and Cox models analyse data. Of 3328 eligible patients, follow-up data were available for 3017 (53% male, mean follow-up: 84.5 ± 28.9 months). Advanced fibrosis (F3–F4) was present in 1125 (37.3%). The study recorded 593 deaths (2.58/100 person-years), 271 HCC cases (1.24/100 person-years), and 281 decompensated cirrhosis cases (1.30/100 person-years). Advanced fibrosis was associated with increased mortality (HR: 1.72, 95% CI: 1.46–2.03, p < 0.001) and decompensation (HR: 2.23, 95% CI: 1.74–2.85, p < 0.001) but not HCC (HR: 1.17, 95% CI: 0.92–1.49, p = 0.192). Fibrosis reversed in 11.9%, improved in 17.8%, remained stable in 50.5%, and progressed in 19.8%. This decade-long study confirms DAAs improve liver function, reduce mortality, and slow disease progression, reinforcing their role in preventing long-term complications.