December 8, 2017

The short-term incidence of hepatocellular carcinoma is not increased after hepatitis C treatment with direct-acting antivirals: An ERCHIVES study


Hepatobiliary Malignancies

Darrick K. Li MD, PhD1,6, Yanjie Ren MS2, Daniel S. Fierer MD3, Stephanie Rutledge MD1, Obaid S. Shaikh MD2, Vincent Lo Re III MD, MSCE4, Tracey Simon MD1,6, Abdul-Badi Abou-Samra MD, PhD5,7, Raymond T. Chung MD1,6,* and Adeel A. Butt MD, MS2,5,7,*

DOI: 10.1002/hep.29707

© 2017 by the American Association for the Study of Liver Diseases.


Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Publication History

  1. Accepted manuscript online: 2 DEC 2017 11:21AM EST
  2. Manuscript Accepted: 20 NOV 2017
  3. Manuscript Revised: 12 NOV 2017
  4. Manuscript Received: 6 JUL 2017

Keywords: Cirrhosis; sustained virologic response; interferon; sofosbuvir; Veterans


Recent studies have reported higher rates of hepatocellular carcinoma (HCC) in individuals treated with direct-acting antivirals (DAAs). However, making definitive conclusions has been challenging due to the heterogeneous populations and methodologies of these reports. We investigated whether DAA use is associated with higher rates of incident HCC compared to treatment with interferon-based regimens. We performed a retrospective population-based cohort study using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database. In a cohort of 17,836 persons, SVR was achieved by 66.6% and 96.2% of the IFN and DAA groups, respectively. Among all treated persons, the risk of HCC was not higher in the DAA group compared to the IFN group (HR 1.07; [95% CI: 0.55, 2.08]). Among persons with cirrhosis who achieved SVR, neither the HCC incidence rate nor HCC-free survival were significantly different in the DAA group compared to the IFN group (21.2 vs. 22.8 per 1000 person years; p=0.78; and log-rank p=0.17, respectively). Untreated persons with cirrhosis had a significantly higher HCC incidence rate (45.3 per 1000 person years) compared to those treated with either IFN or DAAs (p=0.03). Both groups of treated persons had significantly lower probability of HCC development compared to untreated persons (log-rank p=0.0004).

Conclusions: DAA treatment is not associated with a higher risk of HCC in cirrhotics with chronic HCV infection in the short-term. Previously reported higher rates of HCC associated with DAA treatment may be explained by both the presence of relatively fewer baseline HCC risk factors in persons treated with IFN as well as selection bias, as DAA regimens were used to treat persons at higher risk for developing HCC. This article is protected by copyright. All rights reserved.


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