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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.

Original publication

DOI

10.1136/gut.52.8.1206

Type

Journal article

Journal

Gut

Publication Date

08/2003

Volume

52

Pages

1206 - 1210

Addresses

Hepatology Section, Division of Medicine A, Imperial College School of Medicine at St Mary's Hospital, Praed St, London W2 1NY, UK. mark.wright@ic.ac.uk

Keywords

Humans, Hepatitis C, Chronic, Liver Cirrhosis, Disease Progression, Factor V, Multivariate Analysis, Sensitivity and Specificity, Genotype, Polymorphism, Genetic, Adult, Female, Male