Clinical Outcomes of Upfront Combination Therapy for Portopulmonary Hypertension

Background Limited data exists on upfront combination therapy for portopulmonary hypertension. We evaluated the clinical efficacy, long-term outcomes, and safety of upfront combination therapy in patients with portopulmonary hypertension. Methods We performed a retrospective, single-center cohort study involving a final analysis of 33 consecutive patients diagnosed with portopulmonary hypertension who were taking pulmonary arterial hypertension-specific medication. We compared hemodynamic parameters, 4-strata risk profiles, composite clinical worsening events, and safety between monotherapy (n = 23) and upfront combination therapy (n = 10). Results Twenty-seven patients (82%) were classified into the Child–Pugh A stage. The change ratios of pulmonary vascular resistance (-32% vs. -57%, P = 0.006) were significantly better with upfront combination therapy. Upfront combination therapy also showed significant improvement in risk profiles. Kaplan–Meier analysis showed that the composite event-free rate was significantly lower in patients who received upfront combination therapy than in those who received monotherapy (P = 0.016), although no statistical differences were observed in all-cause death. In the univariate Cox proportional hazards analysis, upfront combination therapy was a factor for decreasing composite clinical worsening outcomes (hazard ratio 0.190, 95% confidence interval 0.042–0.854; P = 0.030). No significant hepatic impairments were observed over 2 years of follow-up in the upfront combination group. Conclusions In patients with portopulmonary hypertension, upfront combination therapy significantly improved symptoms and short-term hemodynamics, and reduced long-term clinical worsening events without serious adverse effects. This study’s findings suggest that patients with portopulmonary hypertension presenting with mild hepatic impairment benefit from upfront combination therapy.