Factor V Leiden polymorphism and the rate of fibrosis development in chronic hepatitis C virus infection.
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.
Wright
M
M
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
Goldin
R
R
Hellier
S
S
Knapp
S
S
Frodsham
A
A
Hennig
B
B
Hill
A
A
Apple
R
R
Cheng
S
S
Thomas
H
H
Thursz
M
M
D000328:Adult; D018450:Disease Progression; D005165:Factor V / Q000235:genetics*; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics*; D008297:Male; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic / Q000235:genetics*; D012680:Sensitivity and Specificity
C095381:factor V Leiden; D005165:Factor V