Prevalence of inherited antithrombin, protein C, and protein S deficiencies in portal vein system thrombosis and Budd-Chiari syndrome: a systematic review and meta-analysis of observational studies

Background and aim: The prevalence of inherited antithrombin (AT), protein C (PC), and protein S (PS) deficiencies in portal vein system thrombosis (PVST) and Budd-Chiari syndrome (BCS) are substantially varied in different studies. No quantitative syntheses of these studies have been performed. A systematic review and meta-analysis were conducted to examine the prevalence of inherited AT, PC, and PS deficiencies in these patients and to compare the prevalence with healthy subjects.

Methods: PubMed, EMBASE, and Cochrane Library databases were employed to identify all studies in which inherited AT, PC, and PS deficiencies in PVST and/or BCS were evaluated by family study or gene analysis. Prevalence and odds ratios of these inherited deficiencies were pooled; heterogeneity among studies was evaluated.

Results: Nine studies were included in our meta-analysis. The pooled prevalence of inherited AT, PC, and PS deficiencies were 3.9%, 5.6%, and 2.6% in PVST, and 2.3%, 3.8%, and 3.0% in BCS, respectively. Heterogeneity among studies was not significant except for the analysis of inherited PC deficiency in BCS. Three studies compared the prevalence of these inherited deficiencies between PVST patients and healthy subjects. The pooled odds ratios of inherited AT, PC, and PS deficiencies for PVST patients were 8.89 (95% confidence interval [CI] 2.34-33.72, P = 0.0011), 17.63 (95% CI 1.97-158.21, P = 0.0032), and 8.00 (95% CI 1.61-39.86, P = 0.011), respectively. Only one study demonstrated that no inherited deficiency was found in both BCS patients and healthy subjects.

Conclusions: Inherited AT, PC, and PS deficiencies are rare in PVST and BCS. These inherited deficiencies increase the risk of PVST.