Case report 1117 Efficiency and safety of bosentan in child C cirrhosis with portopulmonary hypertension and renal insufficiency Florian Barth a , Peter J. Gerber a , Ju ¨ rg Reichen b , Jean-Franc ¸ ois Dufour b and Laurent P. Nicod a Bosentan has lately been described as a successful therapeutic agent for portopulmonary hypertension consecutive to child A cirrhosis. This is the first report of the effect of this substance with advanced liver cirrhosis (child C) and renal insufficiency. Low doses of bosentan (initially twice 31.25 mg/day and then 62.5 mg/day) increased cardiac output and allowed correction of renal insufficiency; it allowed one to stop the requirement of oxygen and not only improved the 6-min walking test by more than 400 m, but also decreased the severity of the liver cirrhosis to child B stadium. This suggests that patients, who would be excluded from a liver transplantation program because of their portopulmonary hypertension, could profit from a careful therapy with bosentan. Eur J Gastroenterol Hepatol 18:1117–1119  c 2006 Lippincott Williams & Wilkins. European Journal of Gastroenterology & Hepatology 2006, 18:1117–1119 Keywords: bosentan, cirrhosis, portopulmonary hypertension, renal insuffi- ciency a Clinic and Policlinic of Pneumology, Inselspital and b Institut of Clinical Pathology of the Bern University, Bern, Switzerland Correspondence and requests for reprints to Professor Laurent P. Nicod, Clinic and Policlinic of Pneumology, Inselspital, CH, 3010 Bern, Switzerland Tel: + 41 31 632 34 90; fax: + 41 31 632 98 33; e-mail: laurent.nicod@insel.ch Received 13 March 2006 Accepted 6 May 2006 Introduction Portopulmonary hypertension (PPHTN) is defined as pulmonary artery hypertension (mPAP > 25 mmHg, pulmonary capillary wedge pressure > 15 mmHg and pulmonary vascular resistance > 240 dyn/s/cm 5 [1]) in the presence of portal hypertension and is a severe complication in patients suffering from liver cirrhosis [2,3]. The principle is shear stress from increased pulmonary blood flow, leading to dysfunction of the pulmonary vessel endothelial cells with consecutive proliferation, smooth muscle hypertrophy and vasocon- striction [4]. Elevated endothelin (ET)-1 plasma levels were measured in experimental cirrhosis [5] and in patients with PPHTN [6]. These plasma levels are related on one hand to the severity of the pulmonary disease and on the other hand to the portal pressures [7,8]. Portal hypertension can trigger pulmonary hyper- tension [3]. Clinical trials with bosentan, an endothelin antagonist on both A and B endothelin-1 receptors, have shown promising results in patients with idiopathic pulmonary hypertension and lately in patients with child A cirrhosis and secondary PPHTN [9,10]. The efficiency has also been proven in experimental settings in which bosentan decreased pulmonary and portal pressure [5,11]. Serum aminotransferase levels become elevated in about 10% of patients treated with 125 mg bosentan twice daily [9]. The use of hepatotoxic drugs in child C cirrhosis is critical, because there is no compensatory capacity left for further damage. In this report we describe bosentan treatment of a patient with severe PPHTN, hepatorenal syndrome and child C cirrhosis. Case report A 41-year-old man with liver cirrhosis child C (child-Pugh score 11 points) due to chronic hepatitis C and history of alcohol abuse (abstinent since 2004 for 10 months) was admitted to hospital, complaining of dyspnoea, scored by the American Thoracic Society as ATS III–IV and hepatic encephalopathy. The patient had a 20-year history of smoking ( > 1 pack/day). On physical examination, he was a jaundiced but not wasted patient (body mass index 25.2) with severe ascites and peripheral oedema. Blood pressure was 110/70 mmHg. Auscultation of the lungs and the heart was unremarkable. Lung function testing showed mild to moderate obstruction only (with a forced escipatory volume in 1 s: 53% of predicted volume). Echocardiography and laboratory values were indicative of PPHTN and renal insufficiency. The patient was not able to perform a 6-min walking distance test. Laboratory values included brain natriuretic peptide (BNP) 483 pg/ ml (normal, 4–40 ng/ml [12]), total bilirubin 600 mmol/l, AST 175 U/l, ALT 54 U/l, gGT 124 U/l, alkaline phospha- tase 296 U/l, albumin 16 g/l and creatinine 215 mmol/l. Paracentesis revealed the presence of spontaneous bacterial peritonitis ( > 9000 neutrophils/ml). Therapeutic course and trials Spontaneous bacterial peritonitis was treated with ceftriaxone and encephalopathy was successfully con- trolled with lactulose. The renal function slowly im- proved with hydration. A moderate to severe dyspnoea remained related to the above-mentioned PPHTN. A right cardiac catheterization, showing a systolic 0954-691X  c 2006 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.