HCV Genotype 3 Is Associated With an Increased Risk of Cirrhosis and Hepatocellular Cancer in a National Sample of US Veterans With HCV

Data show that viral genotype 1 may increase the risk of cirrhosis and hepatocellular carcinoma (HCC) compared to genotype 2 in patients with chronic hepatitis C virus (HCV) infection. However, the effect of HCV genotype 3 on cirrhosis and HCC risk is uncertain. We identified patients with active HCV infection, confirmed by positive polymerase chain reaction (PCR) and a known HCV genotype, from the VA HCV Clinical Case Registry between 2000 and 2009. We examined the effect of HCV genotype on the risk of cirrhosis and HCC in a Cox proportional hazards model adjusting for patients' age, period of service (World War I/II, Vietnam era, post-Vietnam era), race, gender, human immunodeficiency virus (HIV) infection, alcohol use, diabetes, body mass index, and antiviral treatment receipt. Of the 110,484 patients with active HCV viremia, 88,348 (79.9%) had genotype 1, 13,077 (11.8%) genotype 2, 8,337 (7.5%) genotype 3, and 1,082 (0.9%) patients had genotype 4 infection. Despite being younger, patients with genotype 3 had a higher risk of developing cirrhosis (unadjusted hazard ratio [HR] = 1.40, 95% confidence interval [CI] = 1.32-1.50) and HCC (unadjusted HR = 1.66, 95% CI = 1.48-1.85) than HCV genotype 1 patients. After adjustment for prespecified demographic, clinical, and antiviral treatment factors, the risk of cirrhosis and HCC was 31% (adjusted HR = 1.31, 95% CI = 1.22-1.39) and 80% (adjusted HR = 1.80, 95% CI = 1.61-2.03) higher in patients with genotype 3 compared to genotype 1 infected patients. Conclusion: HCV genotype 3 is associated with a significantly increased risk of developing cirrhosis and HCC compared to HCV genotype 1. This association is independent of patients' age, diabetes, body mass index, or antiviral treatment.