Background and Aim:  Tissue injury leads to activation of coagulation and generation of thrombin. Inhibition of thrombin receptor protease‐activated receptor 1 (PAR‐1) has been shown to reduce liver fibrosis in animals. This study aimed to evaluate the effect of PAR‐1 gene polymorphism on rate of liver fibrosis (RF) in chronic hepatitis C.

Methods:  Polymorphisms studied: C > T transition 1426 bp upstream of translation start site (‐1426C/T), 13 bp repeat of preceding ‐506 5′‐CGGCCGCGGGAAG‐3′ sequence (‐506I/D), and A > T transversion in intervening sequence (IVS) 14 bp upstream of exon‐2 start site (IVS‐14A/T). A total of 287 European and 90 Brazilian patients were studied.

Results:  1426C/T polymorphism: There was a trend to higher RF in patients with the TT genotype (P = 0.06) and an association between genotype CC and slow fibrosis (P = 0.03) in Europeans. In males, RF was significantly higher in those with the TT genotype compared to CT (P = 0.003) and CC (P = 0.007). There was a significant association between TT and fast fibrosis (P = 0.04). This was confirmed in an independent cohort of Brazilians where RF was higher in TT than in CC (P = 0.03). Analysis of ‐506I/D showed no difference in RF and distribution of slow/fast fibrosis among different genotypes in both populations. Analysis of IVS‐14A/T showed no difference between genotypes.

Conclusion:  In conclusion, these findings suggest that PAR‐1 receptor polymorphisms influence the progression of liver fibrosis.