Portal vein thrombosis and thrombophilia in liver cirrhosis: a role for hyperhomocysteinemia ?

Background: Hyperhomocysteinemia (HHcy) is a risk factor of venous thrombosis. Liver plays a key role in homocysteine (Hcy) metabolism. Portal vein thrombosis (PVT) is a serious complication of liver cirrhosis (LC). Different prothrombotic conditions have been considered as risks factors of PVT in LC; a few data are available about HHcy. Materials and Methods: we studied consecutively 86 cirrhotic patients [33 with PVT (PVT, mean age 64±11, 13 females) and 53 without PVT (LC, mean age 66±9, 22 females), no differences in cirrhosis aetiology among groups]; disease stage (Child-Pugh score), HCC presence, smoking, natural anticoagulants (protein C, S and ATIII) and other thrombophilic factors (Factor VIIIc, LAC , FVL, PTHR A20210), plasma Hcy, Hcy-related vitamin status and MTHFR C677T mutation prevalence were assessed in all patients (table 1). Results: A progressive increase in plasma Hcy levels, an higher prevalence of HHcy with the worsening of liver function; an high prevalence of HHcy in PVT group vs. LC group (63.6% vs.28.3%, p=.002) and a significant association of HHcy with PVT [OR=3.26 (95% CI 1.3 ÷ 8.1, p=.003) were observed.PVT (n=33)CC (n=53)pFVL4 (12.1 %)6 (11.3 %).983°PTHR A2021012 (36.4%)5 (9.4%).004°MTHFR C677→T§25 [13] (75.7%)18 [4] (33.9%).013°High Factor VIIIc**19 (57.5%)19 (35.8%).048°LAC3 (9.1 %)4 (7.5%).893°HCC presence (Y/N)12 (57.1%)17 (47.2%).815°Smokers (Y/N)11 (33 %)18 (33.9%).921°Protein S (%)69.5 ± 21.572.8 ± 23.8.565*Protein C (%)54.5 ± 20.5 56.4 ± 25.1.744*AT III (%)62.8 ± 18.865.3 ± 25.2.662*Factor VIIIc (IU/dl)203 ± 59176 ± 65.062*Homocysteine (mol/L)16.4 ± 6.112.0 ± 6.1.015*§Between square brackets is indicated the prevalence of homozygosis; ** High Factor VIIIc = > 170 IU/dl *** HHcy = > 12 mol/L; °test ; *T-testConclusion: According to our data, HHcy, similarly to other thrombosis risk factors, may play a role in the pathogenesis of TVP in patients affected by liver cirrhosis. Identification of this risk group may be essential to plan clinical prevention strategies especially in patients candidates for surgery or other intervention at risk of PVT.