Long-term follow-up of portopulmonary hypertension: Effect of treatment with epoprostenol

Abstract

Moderate to severe portopulmonary hypertension (PPHTN) increases the risks of orthotopic liver transplantation (OLT).Epoprostenol is an effective treatment of PPHTN, but long-term effects on pulmonary hemodynamics or liver function in PPHTN are poorly defined. We sought to describe the long-term effects of treatment with or without epoprostenol on pulmonary hemodynamics, liver biochemistries, and survival in patients with moderate to severe PPHTN at a single center. A large retrospective cohort was identified with moderate to severe PPHTN diagnosed before OLT. Baseline and follow-up pulmonary hemodynamics and liver biochemistries were compared and outcomes assessed. Nineteen patients were treated with epoprostenol and 17 were not treated with epoprostenol. There were significant improvements in mean pulmonary artery pressure (MPAP, 48.4-36.1 mm Hg; P Ͻ 0.0001), pulmonary vascular resistance (PVR, 632-282 dynes ⅐ s ⅐ cm Ϫ5 ; P Ͻ 0.0001), and cardiac output (5.7 to 7.7 L/min; P ϭ 0.0009) with epoprostenol after a median of 15.4 months. Liver biochemistries did not change significantly, and survival did not seem to differ between the 2 groups (hazard ratio, 0.85; P ϭ 0.77). In the epoprostenol group, patients who survived had greater absolute changes in MPAP, transpulmonary gradient, and PVR than those who died. Two patients in the epoprostenol group successfully underwent OLT. Long-term epoprostenol therapy greatly improves pulmonary hemodynamics in patients with PPHTN. Liver biochemistries are not greatly changed. Survival seemed not to differ between treatment groups. A minority of patients treated with epoprostenol will improve sufficiently to undergo OLT. Liver Transpl 13:875-885, 2007. © 2007 AASLD.Received July 11, 2006; accepted February 25, 2007. Portopulmonary hypertension (PPHTN) is an uncommon complication that affects 1-2% of patients with portal hypertension or cirrhosis and 5-10% of patients being evaluated for liver transplantation. 1 It carries a poor prognosis, with a mean survival of 15 months after diagnosis and a 6-month mortality of 50% in the absence of treatment. 2 The pathophysiology of PPHTN is incompletely understood but involves increased pulmonary vascular resistance (PVR) due to vasoconstriction and progressive pulmonary vascular remodeling. 3 The presence of moderate to severe PPHTN (often characterized by mean pulmonary artery pressures [MPAP] Ն35 mm Hg) increases the perioperative and long-term risks of liver transplantation. 4,5 Mild to moderate PPHTN (often characterized by MPAP Ͼ25 mm Hg) may be reversible after orthotopic liver transplantation (OLT), 6 and good long-term outcomes can be achieved. 7-10 However, severe PPHTN (often characterized by MPAP Ն45 mm Hg) may not be reversible and usually requires long-term therapy after OLT. 4,11 Epoprostenol (prostacyclin, prostaglandin I 2 ) is a potent pulmonary and systemic vasodilator that also reAbbreviations: PPHTN, portopulmonary hypertension; MPAP, mean pulmonary artery pressure; OLT, orthotopic liver transplantation; PCWP, ...

Pulmonary Vascular Complications of Liver Disease

“…Previous retrospective analyses have generally yielded similar estimates (89,(94)(95)(96). Neither the severity of liver disease (89,(97)(98)(99)(100) nor the degree of portal hypertension (as measured by the hepatic venous pressure gradient) (89,97) predict the presence or severity of PoPH.…”

“…Nineteen of these were treated with intravenous epoprostenol, but only five improved sufficiently to be deemed candidates for LT, of whom only two (z6%) underwent LT; both patients had persistent PoPH post-transplant (98). At the Mayo Clinic over 13 years, only 9 out of 74 PoPH cases (12%) received LT, of whom three died, all within 1 month of LT (114).…”

Portopulmonary hypertension and hepatopulmonary syndrome: a clinician-oriented overview

“…In one of the largest series, epoprostenol was shown to improve pulmonary haemodynamics and cardiac output in both the acute and long-term setting [39]. These findings have been reproduced by other authors [40,41]. Other PAs have also been evaluated in the management of POPH.…”

“…Our understanding of the impact of PAH-specific therapies that produce improvements in cardiopulmonary haemodynamics to a mean Ppa ,35 mmHg and a PVR ,250 dyn?s?cm -5 REVIEW: POPH AND HPSon post-transplant outcomes is still evolving. Patients who achieve improvements in mean Ppa and PVR to these levels on therapy should be considered potential candidates for LTx [29,30,40,41].…”

Caring for the orphan's orphan: treatment of patients with portopulmonary hypertension

“…First, this is one of the larger studies of the impact of therapy in PPHTN in the recent era [4][5][6][7][8]. While this distinction is more a testament to the relatively small number of patients with PPHTN included in epidemiological studies rather than the absolute magnitude of the current study sample, clinical researchers need to follow the lead of HOEPER et al [3] in forming multicentre national and international consortia in order to study meaningful numbers of these patients over time.…”