S2433 Evaluating the Effectiveness of Antiviral Therapy in Reducing the Incidence of de novo Hepatocellular Carcinoma in Patients With Compensated HCV-Related Cirrhosis: A Comprehensive Systematic Review and Meta-Analysis

Introduction: Hepatitis C virus (HCV) infection is a major global health concern with Chronic hepatitis C infection being a leading cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide. The introduction of Direct-acting antiviral therapy (DAA) revolutionized management of HCV through a Sustained virologic response and a decrease in liver-related mortality. Our objective was to Evaluate the effect of DAA therapy on the incidence of de novo HCC, focusing specifically on patients with compensated HCV-related cirrhosis. Methods: A comprehensive search was performed on PubMed, Embase, and Cochrane Library for studies comparing the incidence of HCC in patients with compensated cirrhosis due to hepatitis C who received DAA therapy. The main outcomes were incidence rate of de novo HCC rate per 100 PY, cirrhosis status, DAA-treated patients. Statistical analyses were performed using Review Manager 5.4.1 (Cochrane Collaboration). The I2 test was employed for heterogeneity assessment, while the risk of bias was evaluated utilizing ROBINS-I. Results: We included 4,636 patients from 16 observational studies in this meta-analysis. In comparison, the incidence rate of de novo HCC was reduced in the treatment group with a risk ratio (RR) of 0.63 (95% CI 0.56–0.70, P < 0.00001) per 100PY. While incidence and mortality rates in DAA-treated patients were found to be statistically significant. Subgroup analyses based on factors such as sex, age, cirrhosis status (including progression, stability, or regression), Child-Pugh classification, AFP, alanine aminotransferase, and aspartate aminotransferase levels showed no statistically significant differences. Conclusion: The use of DAAs in patients with chronic hepatitis C has generated considerable debate regarding their impact on the development and recurrence of HCC. Initial observational studies and case series raised concerns about decreased rates of de novo HCC following DAA therapy, particularly in patients with advanced cirrhosis. Despite these reassuring data, the controversy persists due to heterogeneity in study populations, timing of antiviral initiation, and follow-up durations, underscoring the importance of further research to clearly delineate the interplay between antiviral therapy and hepatocarcinogenesis.