Sustained HCV Clearance by Interferon-Based Therapy Reduces Hepatocellular Carcinoma in Hepatitis B and C Dually-Infected Patients

Abstract

Background

Recent studies have indicated that interferon (IFN) or pegylated interferon (PEG-IFN) plus ribavirin therapy can achieve sustained virological response (SVR) against HCV equally in dual HBV–HCV infection and in HCV monoinfection. Whether these therapies can reduce hepatocellular carcinoma (HCC) development in dual HBV–HCV infection remains unclear.

Methods

A total of 135 dually-infected patients with active hepatitis C receiving IFN or PEG-IFN plus ribavirin therapy were enrolled. The cumulative incidence of HCC was compared to that in 1,470 HCV-monoinfected patients.

Results

Based on the Cox proportional hazards model, dual infection was an independent factor for HCC development in all 1,605 chronic hepatitis C patients with or without positive hepatitis B surface antigen receiving IFN or PEG-IFN plus ribavirin (hazard ratio (HR)=1.864, 95% CI 1.052–3.303; P=0.033). In dually-infected patients, HCC developed in 4 of 96 with HCV SVR and 11 of 39 without HCV SVR (P<0.001) after a median follow-up of 4.6 years. Age (HR=1.175, 95% CI 1.070–1.291; P=0.001) and non-HCV-SVR (HR=7.874, 95% CI 2.375–26.32; P=0.001) were independent factors for HCC development. Subgroup analysis showed that HCC occurrence was lower in patients with HCV SVR and HBV DNA levels <2,000 IU/ml at the end of treatment or follow-up compared to those with HCV SVR and HBV DNA levels ≥2,000 IU/ml (P=0.034) and those without HCV SVR (P<0.001).

Conclusions

Sustained HCV clearance by IFN or PEG-IFN plus ribavirin therapy may significantly reduce HCC in HBV–HCV dually-infected patients, whereas persistence or reactivation of HBV decreases the benefit of HCV SVR.