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No difference between direct-acting antivirals for hepatitis C in hepatocellular carcinoma risk

Mun, Elijah J.a; Green, Pamelac; Berry, Kristinc; Ioannou, George N.b,c

European Journal of Gastroenterology & Hepatology: January 2019 - Volume 31 - Issue 1 - p 47–52
doi: 10.1097/MEG.0000000000001242
Original Articles: Hepatology

Background and aims It is unclear whether there are differences between direct-acting antivirals (DAAs) for hepatitis C virus in risk of hepatocellular carcinoma (HCC) after antiviral therapy. We aimed to compare different DAA regimens with respect to risk of de novo HCC following antiviral therapy.

Patients and methods We identified 33 137 patients who initiated hepatitis C virus antiviral treatment in the Veterans Affair healthcare system between 6 December 2013 and 31 December 2015 with one of four DAA-only regimens (± ribavirin): paritaprevir/ritonavir/ombitasvir/dasabuvir (n=6289), sofosbuvir (n=4356), sofosbuvir+simeprevir (n=3210), and ledipasvir/sofosbuvir (n=19 282). We retrospectively followed patients until 15 June 2017 to identify incident (de novo) cases of HCC. We used propensity score-adjusted Cox proportional hazards regression to compare different DAA regimens with respect to HCC risk.

Results During a mean follow-up of 1.52 years, 741 new cases of HCC were diagnosed after antiviral treatment (annual incidence=1.47%). Patients treated with sofosbuvir+simeprevir had the highest annual HCC incidence (2.47%), followed by sofosbuvir (1.91%), ledipasvir/sofosbuvir (1.26%), and paritaprevir/ritonavir/ombitasvir/dasabuvir (0.95%). However, there were great differences between DAA-treated patients in the prevalence of cirrhosis, markers of advanced fibrosis, thrombocytopenia, and other HCC risk factors. After adjustment for baseline characteristics associated with HCC, there were no significant differences in HCC risk between the four DAA regimens.

Conclusion There are no significant differences between DAA regimens in HCC risk after antiviral treatment. This suggests that DAAs do not have direct carcinogenic effects as it would be unlikely that different DAAs would have identical carcinogenic effects.

aDepartment of Internal Medicine, University of Washington

bDivision of Gastroenterology, Department of Medicine, Veterans Affairs Puget Sound Healthcare System and University of Washington

cHealth Services Research and Development, Veterans Affairs Puget Sound Healthcare System, Seattle, Washington, USA

Correspondence to George N. Ioannou, BMBCh, MS, Division of Gastroenterology, Veterans Affairs Puget Sound Health Care System, S-111-Gastro, 1660 South Columbian Way, Seattle, WA 98108, USA Tel: +1 206 277 3136; fax: +1 206 764 2232; e-mail:

Received June 6, 2018

Accepted July 10, 2018

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.