Risk of hepatitis C virus related hepatocellular carcinoma between subjects with spontaneous and treatment-induced viral clearance.

Chung Feng Huang ,Gilbert L’Italien,Yong Yuan,Pei‐Chien Tsai ,Hsuan-Shu Lee ,Soa Yu Chan ,Jiun-Chi Huang ,Cheng Fang Huang ,Sheng Lu ,Zu Yau Lin ,Hwai I Yang ,C.-L Jen ,Ming Lun Yeh ,Ming Yu ,Chia Yen Dai ,Lin Yang ,Li Yu Wang ,Wan‐Long Chuang ,Shinn Cherng Chen ,Chien Jen Chen

doi:10.18632/oncotarget.14937

Abstract

Background/AimsBoth spontaneous hepatitis C virus (HCV) clearance and the achievement of sustained virological response (SVR) by anti-viral therapy greatly reduce the incidence of hepatocellular carcinoma (HCC). The current study aimed to compare the risk of HCC between the two patient groupsMethodsA total of 313 subjects with spontaneous HCV clearance (SC) and 564 age- and sex-matched patients in the treatment-induced SVR group were enrolled for analysis.ResultsNineteen (2.2%) of the 877 patients developed HCC during 6,963 person-years of follow-up. Fourteen (2.5%) SVR patients and 5 (1.6%) SC patients developed HCC (P=0.004). Cox regression analysis of factors predictive of HCC included SVR (versus SC: hazard ratio [HR]/ 95% confidence interval [CI]: 5.83/1.27-26.88), diabetes (HR/CI:3.41/1.21-9.58), and age (HR/CI: 1.07/1.01-1.14). Of the 564 SVR patients, eleven (5.9%) of the 187 patients with fibrosis stage 2-4 (F2-4) and 2 (0.9%) of the 226 patients with F01 developed HCC (P=0.01). Compared to SC subjects, only SVR patients with F2-4 (P<0.001) but not F0-1(P=0.60) had a higher risk of HCC development. Cox-regression analysis using liver fibrosis as a variable demonstrated that factors associated with HCC included SVR with F2-4 (versus SC: HR/CI: 10.06/2.20-45.98), diabetes (HR/CI:3.23/1.14-9.19), and age (HR/CI: 1.08 1.02-1.15).ConclusionsCompared to subjects with spontaneous viral clearance, subjects with antiviral treatment-induced HCV viral clearance remain at high risk for HCC development, especially if they have significant hepatic fibrosis. These results may provide important information for decision-making regarding the prioritization of current direct antiviral agents in resource-limited countries.

Highlights

Spontaneous hepatitis C virus (HCV) seroclearance occurs in 20-30% of patients after acute infection [1,2,3]
Cox-regression analysis using liver fibrosis as a variable demonstrated that factors associated with hepatocellular carcinoma (HCC) included sustained virological response (SVR) with fibrosis stage 2-4 (F2-4), diabetes (HR/CI:3.23/1.14-9.19), and age (HR/CI: 1.08 1.02-1.15)
Compared to subjects with spontaneous viral clearance, subjects with antiviral treatment-induced HCV viral clearance remain at high risk for HCC development, especially if they have significant hepatic fibrosis

Summary

Introduction

Spontaneous hepatitis C virus (HCV) seroclearance occurs in 20-30% of patients after acute infection [1,2,3]. The development of successful antiviral therapy (e.g., achievement of sustained virological responses, SVR) with interferon-based therapy could attain a sustainable HCV seroclearance for years [7], significantly reducing the risk of cirrhosis and HCC development [8,9,10]. It is unclear if treatment-induced HCV seroclearance achieved by SVR could decrease the incidence of HCC to a similar rate observed in subjects with self-limited HCV infections. We addressed the issue by conducting an age and sex-matched case-control study using a clinical cohort of chronic hepatitis C (CHC) patients with successful antiviral therapy and a community cohort of patients with spontaneous HCV seroclearance

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Results

Conclusion