The Impact of Thrombophilic Factors on Disease Progression in Children with Biliary Atresia—A Single-Centre Cohort Study

Abstract

Epidemiological evidence suggests that thrombophilic factors, including male sex, non-O blood type, MTHFRnt677TT mutation, factor V Leiden G1691A mutation, and prothrombin G20210A polymorphism, may contribute to the progression of fibrosis and occurrence of portal vein thrombosis in liver disease. We retrospectively investigated the effect of potentially thrombophilic factors on native liver survival as a patient-relevant endpoint of disease progression in a cohort of 142 children being followed up for biliary atresia at Hannover Medical School from April 2017 to October 2019. No significant association could be determined. There was no evidence for relevant differences in native liver survival for the Factor V Leiden G1691A mutation (hazard ratio [HR] = 0.86, 95% confidence interval [CI] 0.38–1.98, p = 0.73), prothrombin G20210A polymorphism (HR = 0.96, 95%CI 0.24–3.65, p = 0.96), non-O blood type (HR = 0.79, 95%CI 0.51–1.21, p = 0.28) or MTHFRnt677TT mutation (HR = 1.24, 95%CI 0.60–2.56, p = 0.56). A certain, albeit not strong, evidence of reduced native liver survival in male patients after Kasai hepatoportoenterostomy, particularly during the first 2000 days (42%; HR = 1.41, 95%CI 0.92–2.18, p = 0.11) was found. All children with pre-transplant portal vein thrombosis (n = 7) had non-O blood types. Larger multi-centre studies are necessary to show if the male sex or other thrombophilic factors could be potentially associated with reduced native liver survival.