Incidence and risk factors of hepatocellular carcinoma change over time in patients with hepatitis C virus infection who achieved sustained virologic response

Aim In patients with chronic hepatitis C, hepatocellular carcinoma (HCC) occurs at a certain frequency, even if a sustained virologic response (SVR) is achieved by antiviral treatment. Old age, liver fibrosis, and high post‐treatment α‐fetoprotein (AFP) level are typical risk factors of post‐SVR HCC. We examined whether the frequencies and factors of HCC in patients with an SVR achieved from interferon treatment changed. Methods Among patients prospectively registered for pegylated interferon and ribavirin treatment, 2021 with an SVR without HCC development during the treatment period were followed up. The mean observation period was 49.5 ± 26.2 months. Results The multivariable Cox regression analysis showed that older age, diabetes mellitus, advanced liver disease, and higher post‐treatment AFP level were the independent risk factors throughout the observation period. The annual occurrence rate of HCC was 0.74% in the third year, 0.54% in the fourth year, and 0.40% in the fifth year; it gradually decreased from the third year. Because the time course hazards for HCC changed at 48 months, we separately analyzed its risk factors before and after this change point. The multivariable Cox regression analysis showed that the four above‐mentioned factors were significantly related to HCC development within 4 years. Conversely, the univariable Cox regression analysis only identified diabetes mellitus as a significant factor for HCC development after 4 years. Conclusion The frequency of HCC in hepatitis C patients who achieved an SVR from interferon treatment decreased during the observation period, and its risk factors changed between the early and late periods.