Vasomodulators and liver transplantation for portopulmonary hypertension: evidence from a systematic review and meta-analysis.

Untreated portopulmonary hypertension (PoPH) carries poor prognosis. Previous reports have described vasomodulator therapy (VM) and liver transplantation (LT) as treatment options. However, no study has systematically summarized the reported effects on pulmonary hemodynamics and survival. We aimed to provide summary estimates on these endpoints in patients with PoPH, treated with different modalities. We performed a systematic review with meta-analysis of mainly observational and case-control studies describing no treatment, VM, LT or VM+LT in patients with PoPH. Twenty-six studies (1019 patients) were included. Both VM and VM+LT improve pulmonary hemodynamics. A substantial proportion of patients treated with VM becomes eligible for LT (44%, 95%CI:31-58). Pooled estimates for 1-, and 3-year post-diagnosis survival in patients treated with VM were 86% (95%CI:81-90) and 69% (95%CI:50-84), versus 82% (95%CI:52-95) and 67% (95%CI:53-78) in patients treated with VM+LT. Of note, studies reporting on the effect of VM mainly included Child-Pugh A/B patients, while studies reporting on VM+LT mainly included Child-Pugh B/C. Seven studies (238 patients) included both patients who received VM only and patients who received VM+LT. The risk of death in VM-only-treated patients was significantly higher than in patients who could be transplanted too (odds ratio 3.5; 95%CI:1.4-8.8), however, importantly, patients who proceeded to transplant had been selected very strictly. In 50% of patients, VM can be discontinued post-LT (95%CI:38-62). Conclusion: VM and VM+LT both improve pulmonary hemodynamics and prognosis in PoPH. In a strictly selected subpopulation of cases where LT is indicated based on severe liver disease and where LT is considered safe and feasible, treatment with VM+LT confers better prognosis. Considering successful VM, 44% can proceed to LT, with half of them being able to postoperatively stop medication.