NIV Congres

Background and aims Microthrombus formation in the microvascular supply of the biliary tree during ischemia intervals throughout the transplantation procedure are thought to be the cause of non-anastomotic biliary strictures (NAS) after liver transplantation. In the Budd-Chiari syndrome (BCS), thrombosis develops in the hepatic venous outflow tract in patients with an underlying thrombotic diathesis and hypofibrinolysis. Compelling data shows that the coagulation and complement systems are co-regulated and highly integrated. Mannose-binding lectin-associated protease (MASP)-2 is a liver-derived essential component of the lectin complement activation pathway and activates pro-urokinase plasminogen activator. About 5% of the Caucasian population is heterozygous for an inherited deficiency of MASP-2. We therefore hypothesized that deficiency of MASP-2 might decrease fibrinolytic potential. Patients and methods: We explored the impact of the MASP2 D120G mutation on the development of NAS in a cohort of 147 liver transplantations. The risk of NAS was assessed by multivariate Cox regression analysis. The analysis was replicated in a validation cohort involving 167 liver transplantations. The risk of BCS was explored in all patients combined.

Results In the discovery study the MASP2 mutation in the donor was accompanied by a significantly increased risk of NAS (adjusted hazard ratio, 6.4; 95% CI, 2.2-19.0; P=0.008), adjusted for factors with p< 0.15 in univariate analysis: recipient age, primary liver disease and ischemia time. In the validation study the MASP2 mutation also increased the risk of NAS (adjusted hazard ratio, 3.0; 95% CI, 1.0-8.9; P< 0.05). Three out of the four patients (75%) with BCS as indication for liver transplantation were heterozygous for MASP2 D120G compared to 4% in patients with other indications for OLT (P=0.0004). In addition, after transplantation two out of three patients who developed BCS received a donor liver heterozygous for the minor G-allele of MASP2 compared to only 5% in patients with other complications after OLT (P=0.009).

Conclusion This study revealed a strong association between the MASP2 D120G mutation and the development of BCS and NAS post-liver transplantation. Based on our findings, there is evidence that BCS and NAS share a similar MASP2-associated pathophysiological mechanism which causes disordered coagulation or fibrinolysis.