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. 2003 Aug;52(8):1206-10.
doi: 10.1136/gut.52.8.1206.

Factor V Leiden polymorphism and the rate of fibrosis development in chronic hepatitis C virus infection

M Wright  1 , R Goldin, S Hellier, S Knapp, A Frodsham, B Hennig, A Hill, R Apple, S Cheng, H Thomas, M Thursz
Affiliations

Factor V Leiden polymorphism and the rate of fibrosis development in chronic hepatitis C virus infection

M Wright et al. Gut. 2003 Aug.

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.

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Figures

Figure 1
Figure 1
Rate of fibrosis by genotype: 95% confidence intervals for loge rate of fibrosis by factor V Leiden genotype (ANOVA, p=0.004).
Figure 2
Figure 2
Stage of fibrosis according to factor V genotype: 95% confidence intervals for stage of fibrosis by factor V Leiden genotype (ANOVA, p=0.01).
See this image and copyright information in PMC

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