Post-treatment fibrotic modifications overwhelm pretreatment liver fibrosis in predicting HCC in CHC patients with curative antivirals

Abstract

Background/aims: Liver fibrosis determined hepatocellular carcinoma (HCC) occurrence in chronic hepatitis C patients with sustained virological response (SVR). We aimed to determine whether post-treatment fibrotic modification overwhelmed pretreatment fibrotic status in terms of long-term HCC prediction.

Methods: 265 SVR patients with paired biopsies before and after antiviral therapy were enrolled for analysis of the association of fibrotic changes with HCC.

Results: Eighteen (6.8%) of the 265 patients developed HCC over 1931 person-years. Cox regression analysis without post-treatment fibrosis as a covariant revealed that factors predicted HCC included age (hazard ratio [HR]/confidence intervals [CI] 1.07/1.01-1.13, p = 0.01), male gender (HR/CI 4.57/1.45-14.36, p = 0.009), diabetes (HR/CI 3.60/1.32-9.85, p = 0.01) and pretreatment advanced fibrosis (HR/CI 2.73/1.05-7.07, p = 0.039). Advanced fibrosis in post-treatment status replaced pretreatment fibrosis as the most critical determinant of HCC when it was included for analysis (HR/CI 3.53/1.34-9.30, p = 0.01). The incidences of HCC among patients with fibrotic modification from F0-2 to F0-2, F34 to F0-2, F0-2 to F34 and F34 to F34 were 0.41%, 0.84%, 1.68%, and 3.05%, respectively (p = 0.004). Compared to patients whose fibrotic stage remained at F0-2 before and after treatment, the HCC risk decreased and did not differ among those whose fibrotic stage improved from F34 to F0-2. However, HCC risk increased significantly and gradually in patients whose fibrotic stages changed from F0-2 to F34 (HR/CI 4.13/1.11-15.36, p = 0.035) and whose fibrotic stages remained at F34 before and after treatment (HR/CI 7.47/2.37-23.55, p = 0.001) (trend p = 0.003).

Conclusions: Post-treatment fibrotic modifications overwhelmed pretreatment fibrotic statuses in predicting HCC.

Keywords: Fibrosis; HCC; HCV; Post-treatment; SVR.