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

BACKGROUND:
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.

FINDINGS:

• 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.

LIMITATIONS:

• 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.

IMPLICATIONS:

• 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.

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

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.