Abstract

Background: Hepatocellular carcinoma (HCC) occurrence after sustained virologic response (SVR) has been observed even in hepatitis C virus (HCV) patients without advanced liver fibrosis. Identifying and stratifying factors associated with HCC occurrence in patients without advanced liver fibrosis will enable efficient post-SVR HCC surveillance. The aim of this study was to develop a scoring system to predict HCC occurrence after SVR in HCV patients without advanced liver fibrosis.

Methods: A total of 1,682 HCV patients without advanced liver fibrosis, defined as fibrosis-4 index (FIB-4 index) less than 3.25, without history of previous HCC who started direct-acting antiviral treatment between September 2014 and October 2020, and achieved SVR at 26 Japanese hospitals were included. We defined SVR as undetectable HCV-RNA at 24 weeks after the end of treatment. The start of the follow-up was set at the time of SVR determination, and patients who experienced HCC occurrence before SVR were excluded. The incidence rates and factors associated with HCC occurrence after SVR were examined.

Results: The median age was 66 years old, 44% of the patients were male, and the median FIB-4 index was 2.02. During the median follow-up of 42.5 months from SVR, HCC occurrence was observed in 28 patients. The cumulative HCC occurrence rates at 3 and 5 years were 1.8% and 2.5%, respectively in patients without advanced liver fibrosis. In the multivariate analysis, baseline age ≥65 years (hazard ratio: 3.380, p = 0.010), alanine aminotransferase (ALT) levels at SVR ≥30 U/l (hazard ratio: 5.973, p < 0.001), and alpha-fetoprotein (AFP) levels at SVR ≥5.0 ng/ml (hazard ratio: 4.060, p = 0.001) were significantly associated with HCC occurrence after SVR. We developed a scoring system to predict HCC occurrence after SVR using these three factors (1 point was added for each factor). The cumulative HCC incidence rates at 3 and 5 years were 6.0% and 7.9% in patients with score of 2 or 3, respectively, and no patients developed HCC in those with score of 0.

Conclusion: Baseline older age, higher ALT levels at SVR and higher AFP levels at SVR were significantly associated with HCC occurrence after SVR in patients without advanced liver fibrosis. We developed a new scoring system using these three factors to enclose patients who need HCC surveillance after SVR, and this score may be useful for stratification of HCC risk in patients without advanced liver fibrosis.