Vasomodulators and Liver Transplantation for Portopulmonary Hypertension: Evidence From a Systematic Review and Meta‐Analysis

Abstract

Background and Aims Untreated portopulmonary hypertension (PoPH) carries a poor prognosis. Previous reports have described vasomodulator (VM) therapy and liver transplantation (LT) as treatment options. We aimed to provide summary estimates on the endpoints of pulmonary hemodynamics and survival in patients with PoPH, treated with different modalities. Approach and Results 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 (1,019 patients) were included. Both VM and VM + LT improve pulmonary hemodynamics. A substantial proportion of patients treated with VM become eligible for LT (44%; 95% confidence interval [CI], 31‐58). Pooled estimates for 1‐, and 3‐year postdiagnosis 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, whereas 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. Risk of death in VM‐only–treated patients was significantly higher than in patients who could be transplanted as well (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). Conclusions 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 a better prognosis. Considering successful VM, 44% can proceed to LT, with half being able to postoperatively stop medication.

The Myths and Realities of Portopulmonary Hypertension

“…According to a recent systematic review of the literature, the combination of PAHtargeted therapy and LT conferred the best prognosis in patients with POPH when LT was considered safe and feasible. (31) In summary, these recently published studies suggest that LT can be beneficial in selected patients with POPH. Reality: National experiences regarding long-term outcomes of popH have been recently described, thus providing insight into the role of lt in popH management.…”

“…In patients that survive this high-risk period, ~50% achieve a clinical and hemodynamic "cure" and are able to discontinue PAH therapy posttransplant without adverse effects. (28,31) Unfortunately, the individual response to LT, which ranges from clinical worsening to resolution of POPH, is unpredictable. According to a recent systematic review of the literature, the combination of PAHtargeted therapy and LT conferred the best prognosis in patients with POPH when LT was considered safe and feasible.…”

Association between the albumin–bilirubin (ALBI) score and severity of portopulmonary hypertension (PoPH): A data‐mining analysis

“…Portopulmonary hypertension (PoPH) is a severe complication of chronic liver disease. [1][2][3] PoPH is a progressive disease with exertional dyspnea, which is characterized by elevated pulmonary vascular resistance and subsequent right heart failure. 4 In the last decade, the treatment of PoPH has been advanced by the development of pulmonary arterial hypertension (PAH)-specific therapies including phosphodiesterase-5 inhibitors and endothelin receptor antagonists (ERAs).…”

Recent advances in the approach to hepatopulmonary syndrome and portopulmonary hypertension

“…Therefore, a logical strategy includes sequential therapy consisting of adequate control of pulmonary hemodynamics with vasomodulators followed by consideration of LT in appropriate candidates to resolve underlying liver disease. A recent metaanalysis evaluated pulmonary hemodynamics and outcomes in POPH patients receiving no treatment, treatment with vasomodulators, LT, or vasomodulators followed by LT (28). Both vasomodulator therapy and vasomodulator therapy followed by LT significantly improved pulmonary hemodynamics and prognosis.…”