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LIVER |
1 Hepatology Section, Division of Medicine A, Imperial College School of Medicine at St Mary’s Hospital, Praed St, London W2 1NY, UK
2 The Wellcome Trust Centre for Human Genetics, University of Oxford, UK
3 Department of Human Genetics, Roche Molecular Systems, Inc, Alameda California 94501, USA
Correspondence to:
Correspondence to:
Dr M Wright, Department of Medicine, Imperial College of Science, Technology and Medicine, St Mary’s Hospital (QEQM Wing), South Wharf Rd, London W2 1NY, UK;
mark.wright{at}ic.ac.uk
ABSTRACT
Background: The rate of progression to cirrhosis varies among individuals chronically infected with the hepatitis C virus (HCV). Coagulation pathway activation in models of hepatic fibrosis suggests variation in coagulation pathway components may influence the rate of fibrosis. We hypothesised that polymorphisms of the coagulation factors II and V affect the rate of progression to cirrhosis in HCV infected subjects.
Methods: We studied the relationship between rate of fibrosis (calculated by dividing the fibrosis stage by duration of infection) and genotypes of specific coagulation pathway genes in 352 White European patients infected with HCV. Genotyping was performed using reverse line blot hybridisation.
Results: The rate of fibrosis was significantly higher in patients with the factor V Leiden genotype (Arg560Gln) (ANOVA, p=0.004). In disease association studies, a significant association was seen (Fisher’s exact test, p=0.029; odds ratio 3.28 for fast progression to cirrhosis (expected to reach cirrhosis in less than 30 years) if heterozygous for factor V Leiden). No associations were seen between factor II genotype and fibrosis rate.
Conclusions: Possession of the factor V Leiden polymorphism significantly increases the risk of rapid disease progression in HCV, suggesting a role for the coagulation system in the pathogenesis of fibrotic liver disease.
Keywords: hepatitis C; fibrosis; rate; factor V Leiden; polymorphism
Abbreviations: HCV, hepatitis C virus; PCR, polymerase chain reaction; ANOVA, analysis of variance; ANCOVA, analysis of covariance
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