Bosentan therapy for portopulmonary hypertension

Abstract

The dual endothelin receptor antagonist bosentan has been approved in several countries for pulmonary arterial hypertension, and patients with portopulmonary hypertension (PPHTN) have not specifically been excluded. However, no data have been published on the efficacy and safety of bosentan in this patient population. Here, the first clinical experiences with bosentan in patients with Child A cirrhosis and severe PPHTN are reported.In total, 11 consecutive patients with cirrhosis and severe PPHTN in New York Heart Association Functional Classes III and IV were treated for .1 yr with bosentan.After 1 yr of treatment with bosentan, all patients showed improved symptoms and exercise capacity. The 6-min walking distance increased from 310¡102 m at baseline to 388¡81 m at 1 yr. Cardiopulmonary exercise testing disclosed a significant increase in peak oxygen uptake, from 12.6¡3.5 to 16.6¡2.8 mL?min -1 ?kg -1 . Pulmonary vascular resistance fell from 944¡519 to 635¡321 dynes?s?L -1. The medication was well tolerated by all patients, and there was no evidence of drug-related liver injury.In conclusion, bosentan proved to be efficacious and safe in a small number of patients with portopulmonary hypertension.

Sildenafil treatment for portopulmonary hypertension

“…In the current retrospective study, a significant clinical, functional and haemodynamic improvement was found over 3 months' treatment with oral sildenafil in patients with severe POPH. Successful treatment of POPH has been reported using prostanoids or endothelin-receptor antagonists, with observation times of 3-12 months [9][10][11][12][13]. Subcutaneous, i.v.…”

“…So far, case reports and a case series have been published showing clinical, functional and haemodynamic benefit on treatment with intravenous and inhaled prostanoids, oral bosentan or combination therapy [9][10][11][12][13].…”

Hepatopulmonary Syndrome and Portopulmonary Hypertension in the Same Patient

“…Conventional treatment consists of fluid overload with diuretics and oxygen but does not improve survival rate [15]. Inhibitors of 1-endothelin as bosentan are an effective treatment in stable hepatic illness, however there is insufficient evidence of its effectiveness in patients with altered hepatic dysfunction [16]. Furthermore, patients treated with bosentan have shown better results in hemodynamic parameters and the 6 minute-walk distance test (6MWD) compared with patients treated with inhaled iloprost [17].…”

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“…[30][31] Use of the endothelin A/B receptor antagonist bosentan currently is under investigation. Hoeper and associates showed the effectiveness of bosentan as monotherapy 32 and in combination with inhaled iloprost 33 for the treatment of POPH. Approximately 10% patients treated with bosentan develop hepatotoxicity due to intracellular bile salt accumulation.…”