Risk of HCC in patients with advanced fibrosis/cirrhosis successfully treated with DAA within the Georgian national hepatitis C elimination program

Abstract

Direct-acting antiviral (DAA) therapy has revolutionized the treatment of hepatitis C virus (HCV) infection, with very high rates of sustained virologic response (SVR) and an excellent safety profile. As a result, the morbidity and mortality associated with HCV has dramatically decreased. However, data on the impact of DAA therapy on the natural history and development of HCC are limited especially in patients with advanced fibrosis/cirrhosis. The aim of the study was to explore the occurrence of HCC in chronic hepatitis C patients with advanced fibrosis/cirrhosis who were successfully treated with DAA within Georgian national hepatitis C elimination program. 

Methods: This longitudinal study included 469 patients with advanced liver fibrosis/cirrhosis (defined by FIB-4 score and transient elsatography), who achieved SVR in 2015-2022 and who were followed through June 2024. We estimated cumulative and annual risks of incident HCC by period of follow-up. All patients included in the study underwent the following investigations: abdominal ultrasound, AFP, liver function tests and transient elastography every 6 months. The diagnosis of HCC was confirmed by MRI and/or liver biopsy (in case of necessity). These patients had neither HCC nor decompensated cirrhosis prior to study

Results: Among the 469 patients with SVR, 36 incident cases of HCC were diagnosed during the mean  5.5 years of follow‐up. Among 36 patients with incident HCC 21 were men and 6 women. Mean age at the time of HCC diagnosis was 49 years. The cumulative 1, 2, 3, 4 and 5- year risks of HCC were 0.4%, 1.5% 3.0%, 4..9% and 7.7% respectively. While annual risk estimates were 0.4%, 1.1%, 1.7%, 2.4% and 4.1% for years 1, 2, 3, 4 and 5 respectively. All patients with incident HCC had liver cirrhosis. Among 36 patients with HCC: 8 patients abused alcohol. 11 patients had HCV genotype 3, 7 patients had Non-alcoholic fatty liver disease (NAFLD), 13 patients had type 2 diabetes, 1 patient had Hodgkin’s lymphoma and no significant comorbidity was documented in 4 patients.

Conclusion: The patients with advanced liver fibrosis/cirrhosis remain at increased risk of developing HCC even after SVR. Therefore all patients with advanced fibrosis/cirrhosis require close surveillance for HCC regardless of SVR. Whether age, NAFLD, diabetes, alcohol abuse or other comorbidities increase the risk of HCC need to be further explored.