February 26, 2014


Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Research Article

Fasiha Kanwal1,2,*, Jennifer R. Kramer1,3,  Jawad Ilyas2, Zhigang Duan3, Hashem B. El-Serag1,2

DOI: 10.1002/hep.27095

Copyright © 2014 American Association for the Study of Liver Diseases

Publication History
Accepted manuscript online: 24 FEB 2014 09:44PM EST
Manuscript Accepted: 20 FEB 2014
Manuscript Revised: 4 FEB 2014
Manuscript Received: 19 NOV 2013

Keywords: Cohort;  longitudinal;  Veterans Administration;  viral factors;  association


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 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, 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, 8337 (7.5%) genotype 3, and 1082 (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% 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 pre-specified 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. (Hepatology 2014;)



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