Survival Outcomes and Impact of Targeted PAH Therapy in Portopulmonary Hypertension in the PVRI GoDeep Meta-Registry

Portopulmonary hypertension (PoPH), a type of pulmonary arterial hypertension (PAH) in patients with liver disease, is associated with high morbidity and mortality. The relationship between cardiopulmonary hemodynamics, PAH therapy, and survival in PoPH remains unclear. We performed a retrospective cohort study of PoPH patients from the international pulmonary hypertension (PH) meta-registry, PVRI GoDeep. PAH was defined by a mean pulmonary arterial pressure > 20 mmHg, pulmonary arterial wedge pressure ≤ 15 mmHg, and a pulmonary vascular resistance (PVR) > 2 Wood Units. PoPH diagnoses were assigned by each center's PH specialist based on international guidelines at the time of enrollment. 246 incident PoPH patients met eligibility criteria and were included in the analysis, equally split between males (51%) and females (49%), with a median age of 54 years. When compared to both patients with IPAH and those with other subtypes of PAH (not classified as PoPH or IPAH), those with PoPH had significantly lower 5-year survival rates (46% vs. 68% vs. 65%, log-rank p < 0.001). Amongst the PoPH patients, however, there was no significant difference in 5-year survival when dichotomized by disease severity, either by a PVR of 5 Wood Units or a CI of 2.5 L/min/m². Treatment of the PoPH patients with PAH-targeted therapies was associated with significantly higher 5-year survival rates compared to those not receiving such treatments, as shown by Kaplan–Meier analysis. This survival benefit was observed for PDE5i (50% vs. 34%, log-rank p = 0.029), ERA (58% vs. 34%, log-rank p < 0.001), and the combination of PDE5i and/or ERA (51% vs. 22%, log-rank p < 0.001), as well as any PAH-targeting treatment (50% vs. 26%, log-rank p = 0.007). Corresponding survival advantage was noted when including only PoPH patients with MELD Score ≥ 13. PoPH is a disease with significantly worse long-term survival than other PAH subtypes, but targeted PAH therapy is associated with a robust survival benefit. Survival did not differ across high-risk PVR and cardiac index thresholds, suggesting the factors that influence prognosis and survival in PoPH may be unique as compared to other PAH subtypes, and warrant further investigation.