Background and aim: Age at portal vein thrombosis (PVT) in liver cirrhosis (LC) carriers of the methylene tetrahydrofolate reductase (MTHFR) rs1801133 (C → T667 transition) polymorphism has never been addressed; we compared age at PVT in LC patients genotyped for the MTHFR and explored the interrelated clinical and laboratory factors predicting age at PVT.
Approach and results: Retrospective cross-sectional cohort study. PVT participants: MTHFR CC n = 36, MTHFR CT n = 53, MTHFR TT n = 19; age, sex, age at PVT, Child-Pugh score, rs1799963 PT polymorphisms (G → A 20,210 transition), plasma HC and natural anticoagulants available for all participants. Age at PVT was lower in MTHFR TT than CT and CC (56 ± 13 vs. 57 ± 13 vs. 64 ± 9 years, p = 0.001); median (IQR) plasma HC was higher in MTHFR TT than in the other groups [(17 (9.4, 23.3) vs 13 (8,14.7) vs 11 (8.9, 12.7) μmol/l, p = 0.03)]. MTHFR TT, male gender and protein C predicted age at PVT (p = 0.02, p = 0.04 and p = 0.08); MTHFR TT and Child-Pugh score predicted plasma HC (p = 0.005 and p = 0.01) as well as low plasma protein C (p < 0.0001 and p = 0.0002). Plasma HC inversely related to protein C in the MTHFR TT group (p < 0.0001). Compound MTHFR TT with PT GA had lower age at PVT compared to MTHFR TT alone (49 ± 18 vs 58 ± 12 years).
Conclusions: MTHFR TT anticipates PVT associated with LC by an average of 8 years; MTHFR TT associates with severity of liver disease and to high plasma HC; the latter may contribute to the prematurity of PVT by interfering with the anticoagulant activity of protein C.
Keywords: Child–Pugh score; Homocysteine; Protein C.
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.