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Publication Briefs

Direct-Acting Antiviral Agents Reduce Risk of Hepatocellular Cancer among Veterans with Hepatitis C

In the United States, hepatocellular cancer (HCC) is the fastest growing cause of cancer-related deaths. Chronic infection with hepatitis C virus (HCV) is the leading risk factor for HCC; however, with the advent of highly effective and well-tolerated direct-acting antiviral agents (DAA), HCV treatment rates and the number of patients cured of HCV have increased dramatically. It is expected that within the next decade, most HCV patients seen in U.S. clinical practice will likely be in sustained virological response (SVR) [HCV not detected in the blood 24 weeks after completion of antiviral therapy]. This large cohort study examined the risk of hepatocellular cancer following SVR among 22,500 Veterans with HCV who received DAA treatment at any of 129 VA hospitals between January and December 2015. This timeframe allowed >6 months for treatment completion and SVR testing by September 30, 2016 (end of study follow-up) for all patients. The primary outcome was new cases of HCC after completing treatment with direct-acting antiviral agents. Investigators also examined several variables including demographics, cirrhosis, HCV genotype, previous HCV treatment, HIV, substance use, medical comorbidity, and healthcare use.


  • In Veterans treated with direct-acting antiviral agents, SVR was associated with a 76% reduction in the risk of developing hepatocellular cancer compared to those who did not achieve SVR. This benefit persisted even after accounting for demographic and clinical variables.
  • Patients with cirrhosis had the highest annual incidence of HCC after SVR, ranging from 1.0% to 2.2% per year based on other demographic and clinical characteristics. In contrast, the risk of HCC was low in almost all Veterans without cirrhosis, with the exception of patients with a high baseline FIB-4 that suggested the presence of advanced fibrosis.
  • There was no evidence to suggest that DAAs promote HCC either during or after treatment completion, as some previous studies have suggested.
  • African American Veterans had a lower, whereas Hispanic Veterans had a higher risk of developing HCC compared with whites, although the latter effect did not reach statistical significance.


  • Delaying treatment for HCV until patients progress to cirrhosis might be associated with substantial downstream costs incurred as part of life-long HCC surveillance and/or management of HCC.


  • Findings were limited by short average follow-up time. Risk of HCC and the protective effect of treatment might change as time from treatment elapses.

This study was supported by HSR&D. Drs. Kanwal and Kramer are part of HSR&D's Center for Innovations in Quality, Effectiveness and Safety (IQuESt) in Houston, TX, and Dr. Asch is part of HSR&D's Center for Innovation to Implementation (Ci2i) in Palo Alto, CA.

PubMed Logo Kanwal F, Kramer J, Asch S, et al. Risk of Hepatocellular Cancer in HCV Patients Treated with Direct-Acting Antiviral Agents. Gastroenterology. October 2017;153(4):996-1005.

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What are HSR Publication Briefs?

HSR requires notification by HSR-funded investigators about all articles accepted for publication. These journal articles are reviewed by HSR and publication briefs or summaries are written for a select number of articles that are then forwarded to VHA Central Office leadership to keep them informed about important findings or information. Articles to be summarized are selected by HSR based on timeliness of the findings, interest of leadership, or potential impact on the organization. Publication briefs are written for only a small number of HSR published articles. Visit the HSR citations database for a complete listing of HSR articles and presentations.

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