Acute and long-term effects of inhaled iloprost in portopulmonary hypertension

Abstract

Portopulmonary hypertension (PoPH) is a serious condition without an established treatment. Drugs used to treat pulmonary hypertension may have detrimental effects on portal hypertension. This study was designed to assess in patients with PoPH the acute effects of inhaled iloprost (iILO) on pulmonary and hepatic hemodynamics and to evaluate the clinical outcome after 12 months of treatment. We conducted 2 separate studies. In the first one, 21 patients with PoPH were acutely tested with 2.8 lg of iILO. Pulmonary and hepatic hemodynamics were assessed at the baseline and through 60 minutes after iILO. In the second one, we retrospectively evaluated 12 patients treated with iILO (30 lg/day) for more than 1 year. The 6-minute walk distance (6MWD), functional class (FC), and echocardiogram were analyzed at the baseline and after 12 months of treatment. In the acute study, iILO rapidly reduced pulmonary artery pressure (PAP; À16% 6 8%, P < 0.001) and pulmonary vascular resistance (À18% 6 14%, P < 0.001). The cardiac output did not change initially but decreased after 30 minutes. The hepatic venous pressure gradient (HVPG) and hepatic blood flow did not vary through the study. Pulmonary vasodilation induced by iILO was inversely related to HVPG. In the long-term evaluation, iILO improved FC by 1 or more in 7 patients (P ¼ 0.04) and increased 6MWD by 67 6 59 m at 12 months (P < 0.001). No change in systolic PAP was observed. Two patients died because of hepatic complications, and 4 additional patients presented clinically significant events that were related to hepatic disease in 2 and worsening of pulmonary hypertension in 2. We conclude that in patients with PoPH, iILO produces rapid and selective pulmonary vasodilation without altering the hepatic hemodynamics. Its long-term use may provide sustained improvements in symptoms and exercise tolerance in some patients with PoPH. A randomized, controlled trial is warranted to establish its clinical role in this serious condition.

Cardiac Disease Evaluation and Management Among Kidney and Liver Transplantation Candidates

“…Patients who have an excellent response to treatment have outcomes after liver transplantation comparable to those of other transplantation candidates. 276,277 …”

Portopulmonary hypertension and hepatopulmonary syndrome: a clinician-oriented overview

“…Another patient with severe POPH was successfully bridged to LTx with continuous intravenous iloprost and was without PAH after 2 yrs of follow-up [43]. Recently, MELGOSA et al [44] showed both acute and sustained haemodynamic and clinical improvement over a period of 12 months in POPH patients receiving inhaled iloprost. Generally, PAs are well tolerated with minimal adverse effects that include flushing, headaches and cough.…”

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“…8,18,[24][25][26][27] Epoprostenol binds to endothelial receptors, resulting in increased cyclic adenosine monophosphate levels in the cytosol. This leads to smooth muscle relaxation with subsequent vasodilation.…”