The risk of hepatocellular carcinoma in cirrhotic patients with hepatitis C and sustained viral response: role of the treatment regimen

Hamish A. Innes (Lead / Corresponding author), Stephen T. Barclay, Peter C. Hayes, Andrew Fraser, John F. Dillon, Adrian J. Stanley, Andy Bathgate, Scott A. McDonald, David Goldberg, Heather Valerio, Ray Fox, Nick Kennedy, Pete Bramley, Sharon J. Hutchinson

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    Background: Previous studies have reported a high frequency of hepatocellular carcinoma (HCC) occurrence in patients with advanced liver disease, after receipt of interferon(IFN)-free therapy for hepatitis C virus (HCV) infection. Our objective was to verify and account for this phenomenon using data from the Scottish HCV Clinical Database.

    Methods: We identified HCC-naïve individuals with liver cirrhosis receiving a course of antiviral therapy in Scotland from 1997-2016 resulting in a SVR. Patients were followed-up from their treatment start date to the earliest of: date of death, date of HCC occurrence, or Jan 2017. We used Cox regression to compare the risk of HCC occurrence according to treatment regimen after adjusting for relevant co-factors (including: demographic factors; baseline liver disease stage; comorbidities/health behaviours, virology, and previous treatment experience). HCC occurrence was ascertained through the both the HCV clinical database and medical chart review. For our main analysis, treatment regimen was defined as IFN-free versus IFN-containing.

    Results: 857 patients met the study criteria, of whom 31.7% received an IFN-free regimen. Individuals receiving IFN-free therapy were more likely to be: older; of white ethnicity, Child-Turcotte-Pugh B/C vs. Child-Turcotte-Pugh A; thrombocytopenic; non-genotype 3; and treatment experienced. HCC occurrence was observed in 46 individuals during follow-up. In univariate analysis, IFN-free receipt was associated with a significantly increased risk of HCC (HR: 2.48; P=0.021). However after multivariate adjustment for baseline factors, no significant risk attributable to IFN-free therapy persisted (aHR: 1.15, P=0.744).

    Conclusion: These findings suggest that the higher incidence of HCC following SVR with IFN-free therapy relates to baseline risk factors/patient selection, and not the use of IFN-free therapy per se.

    Lay Summary: We examined the risk of liver cancer among 857 patients with cirrhosis in Scotland who received hepatitis C antiviral therapy and achieved a cure. We compared the risk of first-time liver cancer in patients treated with the newest interferon-free regimens, to patients treated with interferon. After accounting for the different characteristics of these two treatment groups, we found no evidence that interferon-free therapy is associated with a higher risk of liver cancer.

    Original languageEnglish
    Pages (from-to)646-654
    Number of pages10
    JournalJournal of Hepatology
    Issue number4
    Early online date15 Nov 2017
    Publication statusPublished - Apr 2018


    • Hepatocellular carcinoma
    • Interferon-free therapy
    • Direct acting antivirals
    • Sustained viral response
    • Cirrhosis


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