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Hepatotoxicity by bosentan in a patient with portopulmonary hypertension: a case-report and review of the literature.

Author(s): Eriksson C, Gustavsson A, Kronvall T, Tysk C

Affiliation(s): Department of Medicine, Division of Gastroenterology, Orebro University Hospital, Orebro, Sweden.

Publication date & source: 2011-03, J Gastrointestin Liver Dis., 20(1):77-80.

Publication type: Case Reports; Review

Bosentan is an endothelin receptor antagonist approved for treatment of pulmonary arterial hypertension. Mild liver reactions occur in about 10% of treated patients but severe hepatotoxicity is rare. We present clinical data and treatment outcome of a severe drug induced liver injury due to bosentan in a patient with non-cirrhotic portopulmonary hypertension. After 18 months of uncomplicated therapy with bosentan 125 mg b.i.d., the patient developed a severe mixed hepatic injury. Serum levels of bilirubin were 316 micromol/l (ref. value <20 micromol/l), AST 14 microkat/l (ref. value < 0.9 microkat/l), ALT 10 microkat/l (ref. value < 0.9 microkat/l), ALP 8 microkat/l (ref. value <1.8 microkat/l) and INR 1.8 (ref. value 0.9-1.1). Complete diagnostic work-up disclosed no other cause of hepatotoxicity. Treatment with prednisolone 40 mg/day in tapering doses was ultimately added and the patient made a full recovery. Subsequent treatment with sildenafil and ambrisentan for pulmonary arterial hypertension was well tolerated and liver function tests have remained normal during 12 months' follow-up. A review of the literature revealed three other women with severe hepatotoxicity due to bosentan. Bosentan may cause severe liver injury, even after long uneventful therapy, and current recommendations on regular monitoring of liver function tests are reinforced. Ambrisentan may be a therapeutic alternative in patients with pulmonary arterial hypertension and hepatotoxicity by bosentan.

Page last updated: 2011-12-09

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