Portopulmonary hypertension in non-transplanted patients: Results of the largest US single institution registry

Introduction: Portopulmonary Hypertension (PoPH) is a rare disease with poor prognosis affecting patients with liver disease. Medical therapy and, when feasible, liver transplantation (LT), improve outcomes. Clinical characteristics, risk profile and outcomes in the current era of pulmonary artery targeted therapies without LT are not well known.

Methods: From the largest US, single-institution registry of patients with PoPH, we analysed 160 patients between 1988 and 2019 who did not receive LT. Pulmonary arterial hypertension (PAH)-pertinent characteristics, hemodynamics, treatments and risk stratification were compared at baseline, first follow-up visit and at censor/death time.

Results: Median survival for the entire cohort was 27.5 months from the diagnosis of PoPH. Overall survival was 92, 89, 77, 62 and 38% at 3 and 6 months, 1, 2 and 5 years, respectively. Survival was significantly affected by the severity of liver disease (P < 0.001). Uncontrolled PAH was the most common reason for LT denial (108, 67%). The majority of patients received PAH-specific therapies (136, 85%), mostly with monotherapy (123, 77%). With treatment, significant improvements were noted in World Health Organization (WHO) functional class (P = 0.04), 6-min walk distance (P < 0.001), right ventricular function (P < 0.001), pulmonary vascular resistance (P < 0.001) and REVEAL lite-2 score (P = 0.02) univariately. Per ESC risk stratification, no patient met full criteria for low risk at baseline or at follow-up. In the multivariate regression risk model, 6-min walk distance, right atrial pressure, pulmonary capillary wedge pressure, bilirubin level and model for end-stage liver disease (MELD) ≥ 15 were associated with an increased risk of death.

Conclusion: Patients with PoPH who did not undergo LT had a poor prognosis. This persisted despite utilization of PAH-specific therapies, significant improvements in hemodynamics, echocardiography parameters of right ventricular function, 6-min walk distance and WHO functional class.