Prothrombotic genetic risk factors are associated with an increased risk of liver fibrosis in the general population: The Rotterdam Study

Background & Aims The coagulation system is known to be involved in fibrogenesis in patients with liver disease. We investigated whether common genetic prothrombotic risk factors are associated with an increased risk of fibrosis in the general population. Methods This investigation was part of the Rotterdam Study, an ongoing, population-based cohort study. Liver stiffness (LS) was measured using transient elastography (Fibroscan®) and associated with single nucleotide polymorphisms determining blood group type and presence of the Factor V Leiden (FVL) mutation or prothrombin G20210A gene variant. Results Reliable LS measurements and genetic data were obtained from 1055 Caucasian participants. LS ≥8.0 kPa, suggestive of clinically relevant fibrosis, was observed in 101 subjects (9.6%). Presence of FVL or prothrombin G20210A was independently associated with an increased risk of LS ≥8.0 kPa (OR 2.09, 95%CI 1.07-4.07, p = 0.03). Combination of blood group type non-O and the FVL mutation or prothrombin G20210A variant resulted in an even higher risk of LS ≥8.0 kPa (OR 3.36, 95%CI 1.50-7.56, p = 0.003). Presence of the FVL mutation or prothrombin G20210A variant in participants with blood group non-O was associated with a predicted probability of 14.3% (7.7-23.8) of LS ≥8.0 kPa. Conclusions Participants carrying the FVL mutation or prothrombin G20210A variant have an increased risk of clinically relevant liver fibrosis, which is even higher in blood group type non-O carriers. The fact that genetic prothrombotic risk factors are associated with an increased risk of liver fibrosis suggests that coagulation plays an important role in fibrogenesis in the general population.

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