Talk to the Veterans Crisis Line now
U.S. flag
An official website of the United States government

VA Health Systems Research

Go to the VA ORD website
Go to the QUERI website
Publication Briefs

Hepatitis C Virus Genotype 3 Associated with Increased Risk of Cirrhosis and Hepatocellular Cancer among Veterans

Of the estimated 4 million persons in the U.S. who are chronically infected with hepatitis C virus (HCV), up to one-third will progress to advanced fibrosis and cirrhosis – a subset at high risk for subsequent complications, including hepatocellular cancer (HCC). Several published studies show that HCV genotype 1 infection, the most common genotype, may increase the risk of cirrhosis and HCC compared to genotype 2 and other HCV genotypes. Less is known about genotype 3, but some studies suggest it may be associated with accelerated disease progression. Investigators in this retrospective cohort study identified 110,484 Veterans with chronic HCV infection and an average follow-up of more than five years to examine the differences between HCV genotypes in the risk of progression to cirrhosis and HCC. Using data from VA's HCV Clinical Case Registry, which contains health information for all known HCV-infected VA patients, investigators assessed demographics, lab test results, pharmacy data, and inpatient and outpatient diagnoses for Veterans diagnosed with HCV in the VA healthcare system between FY00 and FY09. Risk factors for disease progression, including alcohol use, obesity, HIV infection, and receipt and success of antiviral treatment were also examined.


  • HCV genotype 3 (present in 8% of all cases) was associated with a significantly increased risk of developing cirrhosis and HCC compared to HCV genotype 1 (80% of cases). Veterans with HCV genotype 3 were 31% and 80% more likely to develop cirrhosis and HCC, respectively, compared to Veterans with the most common HCV genotype 1 infection. Adjusting for potential confounders did not change the magnitude or direction of the associations between genotype 3 and cirrhosis or HCC.
  • Genotype 3 has traditionally been considered easier to treat than genotype 1 infection. Investigators found that a significantly higher proportion of Veterans with genotype 3 received and subsequently responded to antiviral treatment than those with genotype 1. However, this therapeutic advantage did not counterbalance the negative impact of genotype 3 on cirrhosis and HCC.


  • Results were limited by the validity of the ICD-9 coding system, which may vary within VA facilities, as well as between VA and non-VA practitioners.
  • While investigators accounted for dispensed prescriptions, they did not have information on adherence with HCV antiviral medication and, therefore, were unable to account for differences in treatment adherence across patients with different genotypes.


  • Given the accelerated progression to advanced liver disease, patients with HCV genotype 3 may serve as a high-risk group that will need to be prioritized in the era of new antiviral treatments.

Drs. Kanwal, Kramer, and El-Serag are part of HSR&D's Center for Innovations in Quality, Effectiveness, and Safety in Houston, TX.

PubMed Logo Kanwal F, Kramer J, Ilyas J, Duan Z, and El-Serag H. HCV Genotype 3 is Associated with an Increased Risk of Cirrhosis and Hepatocellular Cancer in a National Sample of U.S. Veterans with HCV. Hepatology February 24, 2014;e-pub ahead of print.

Related Briefs

» next 15 Hepatitis C Briefs...

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.

Questions about the HSR website? Email the Web Team

Any health information on this website is strictly for informational purposes and is not intended as medical advice. It should not be used to diagnose or treat any condition.