Abstract / Summary
Abstract Background and Aims The contribution of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC) has changed with advances in vaccination and antiviral therapy. We aimed to quantify their global contribution and evaluate geographic and temporal variations. Methods We performed a systematic review and meta-analysis of observational studies reporting HBV or HCV infection among HCC patients. PubMed, Embase, Web of Science, and Cochrane databases were searched from inception to February 19, 2026. Random-effects models were used to estimate pooled proportions. Global estimates were generated by weighting country-specific estimates according to HCC incidence from GLOBOCAN 2022. Temporal trends were assessed using nonlinear meta-regression with restricted cubic splines. Results A total of 344 studies including 878,083 HCC patients were included. HBV infection was identified in 50.4% of patients and HCV infection in 25.8%. HBV was the predominant viral etiology in East Asia, Southeast Asia, and sub-Saharan Africa, whereas HCV contribution was highest in North Africa and the Middle East, Central Asia, and high-income North America. Temporal analyses showed a decline in HBV-associated HCC during earlier decades followed by an increase after approximately 2010. HCV-associated HCC demonstrated a nonlinear pattern, increasing in earlier decades and declining after a peak around 2005. HBV&HCV co-infection accounted for 4.4% of HCC cases globally. Conclusions The viral etiology of HCC is changing worldwide despite advances in hepatitis prevention and treatment. Continued identification and surveillance of individuals with chronic HBV or HCV infection remain essential for reducing the global burden of HCC.