Risk of Hepatocellular Carcinoma After Spontaneous Clearance of Hepatitis C Virus and in Noncirrhosis Chronic Hepatitis C Patients With Sustained Virological Response: A Systematic Review

Abstract

In a hepatitis C virus (HCV)-controlled human infection model (CHIM), healthy volunteers are inoculated with HCV and then treated. Residual hepatocellular carcinoma (HCC) risk after viral clearance is an important consideration when evaluating the CHIM. We estimate HCC risk in spontaneously cleared HCV and in noncirrhosis after sustained virological response (SVR) to HCV treatment in a systematic review and using data from 3 cohorts: German anti-D, Taiwan, and US Veterans Affairs (VA). For noncirrhosis SVR, the overall HCC rate is 0.33 per 100 patient-years in meta-analysis. HCC rates for the German, Taiwan, and US Veterans Affairs cohorts are 0, 0.14, and 0.02 per 100 patient-years, respectively. Past hepatitis B virus exposure was not accounted for in the Taiwan cohort, while VA patients were likely tested based on liver disease/risk factors, which may confound HCC outcomes. The German cohort with no HCC after 44 years is most comparable to the CHIM participants. Although it is difficult to precisely estimate HCC risk from an HCV CHIM, the data suggest the risk to be very low or negligible.

Keywords: hepatitis C; hepatocellular carcinoma risk; noncirrhosis.

Figure 1.

Overall Hepatocellular carcinoma (HCC) Incidence in Chronic Hepatitis C Noncirrhosis Patients Who Achieve Sustained virological response (SVR). Studies that provide HCC outcomes in patients with chronic hepatitis C without cirrhosis and achieved SVR. Studies are grouped according to whether patient-year follow-up was provided or estimated. Time specifies patient-years of follow-up. “Noncirrhosis Pt Yrs” are studies where HCC incidence is calculated based on actual patient-year follow-up provided on noncirrhosis SVR patients. “Estimated, Noncirrhosis Only” are studies where patient-year follow-up is estimated by multiplying sample size of noncirrhosis SVR patients times median/mean follow-up of noncirrhosis SVR patients. “Estimated, Includes Cirrhosis Patients” are studies where patient-year follow-up is estimated by multiplying sample size of noncirrhosis SVR patients times median/mean follow-up of entire cohort (including cirrhosis SVR patients). Abbreviations: CI, confidence interval; DAA, direct-acting antiviral; IFN, interferon; N_Pts, number of patients; Pt Yrs, patient-years.

Figure 2.

Overall hepatocellular carcinoma incidence according to method of cirrhosis diagnosis. Hepatocellular carcinoma incidence grouped according to technique used to diagnose cirrhosis. “Biopsy/Elastography” are studies that diagnosed cirrhosis based on liver biopsies or transient elastography (Fibroscan). “FIB-4 or ICD codes” are studies that diagnosed cirrhosis based on FIB-4 values (>3.25 KPa) or ICD codes. Abbreviations: CI, confidence interval; DAA, direct-acting antiviral; FIB, ICD, International Classification of Diseases, Tenth Revision, Clinical Modification; FIB-4, Fibrosis-4; IFN, interferon; N_Pts, number of patients.