title: HCV genotype 3 is associated with an increased risk of cirrhosis and hepatocellular cancer in a national sample of U.S. Veterans with HCV.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinical Epidemiology and Outcomes Program, Houston VA Health Services Research and Development Center of Excellence, Center for Innovations in Quality, Effectiveness, and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX; Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX.
authors.forename: Fasiha
authors.initials: F
authors.lastname: Kanwal
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Kramer
authors.forename: Jawad
authors.initials: J
authors.lastname: Ilyas
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Duan
authors.forename: Hashem B
authors.initials: HB
authors.lastname: El-Serag
mesh_terms: D000328:Adult; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000453:epidemiology* / Q000821:virology; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000453:epidemiology* / Q000821:virology; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D014728:Veterans / Q000706:statistics & numerical data*; D047829:Vietnam Conflict