Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
J Gastrointestin Liver Dis. 2011 Mar;20(1):77-80.
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 µmol/l (ref. value <20 micromol/l), AST 14 µkat/l (ref. value < 0.9 µkat/l), ALT 10 µkat/l (ref. value < 0.9 µkat/l), ALP 8 µkat/l (ref. value <1.8 µkat/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.
波生坦是一种内皮素受体拮抗剂，已被批准用于治疗肺动脉高压。约 10%的治疗患者会出现轻度肝反应，但严重肝毒性很少见。我们报告了一位非肝硬化门肺高压患者因波生坦引起的严重药物性肝损伤的临床数据和治疗结果。在接受波生坦 125mg 每日两次治疗 18 个月后，患者出现严重混合性肝损伤。血清胆红素水平为 316µmol/l（参考值<20µmol/l），AST 14µkat/l（参考值<0.9µkat/l），ALT 10µkat/l（参考值<0.9µkat/l），ALP 8µkat/l（参考值<1.8µkat/l）和 INR 1.8（参考值 0.9-1.1）。全面的诊断检查未发现其他肝毒性原因。最终加用泼尼松龙 40mg/天逐渐减量治疗，患者完全康复。随后因肺动脉高压改用西地那非和安立生坦治疗，耐受性良好，12 个月随访期间肝功能检查均正常。文献复习显示，另有 3 名女性因波生坦引起严重肝毒性。波生坦甚至在长期无并发症治疗后也可能引起严重肝损伤，因此加强了定期监测肝功能检查的建议。对于因波生坦引起肝毒性的肺动脉高压患者，安立生坦可能是一种治疗选择。
