iloprost and Liver-Cirrhosis

Portopulmonary hypertension (PPHTN) is associated with poor prognosis and high perioperative mortality after orthotopic liver transplantation. This study documents the first case of a patient with PPHTN who was successfully bridged to orthotopic liver transplantation with i.v. iloprost, a stable prostacyclin analogue. The PPHTN had resolved completely 4 months after successful transplantation. In conclusion, portopulmonary hypertension is a relative contraindication to orthotopic liver transplantation, which should be attempted only if pulmonary haemodynamics improve with prostanoids. In this context, iloprost may be a valuable alternative to epoprostenol.

Topics: Alcoholism; Carcinoma, Hepatocellular; Hepatitis C, Chronic; Humans; Hypertension, Portal; Hypertension, Pulmonary; Iloprost; Infusions, Intravenous; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Middle Aged; Preoperative Care; Vasodilator Agents

We report the case of a 43-year-old male with liver cirrhosis based on a chronically active hepatitis C.. Before liver transplantation right-ventricular pressure values of 36 mmHg (+ central venous pressure) were measured whereas, after transplantation, he developed severe pulmonary hypertension with pressure values up to 90 mmHg. These elevated pressure values correlated inversely with graft function. Given the diagnosis of portopulmonary hypertension, we initiated treatment with intravenous epoprostenol and inhalative iloprost but both treatments were not tolerated because of systemic side effects. A combined heart-lung transplantation was considered but the patient died from insufficient cardiac function.. The case report discusses the present diagnostic and therapeutic state of the art in portopulmonary hypertension and reveals basic problems of the present screening strategy.

Topics: Adult; Antihypertensive Agents; Drug Combinations; Epoprostenol; Fatal Outcome; Hepatitis C; Humans; Hypertension, Pulmonary; Iloprost; Liver Cirrhosis; Liver Transplantation; Male; Treatment Failure; Vasodilator Agents

Topics: Adult; Antihypertensive Agents; Drug Combinations; Epoprostenol; Hepatitis C; Humans; Hypertension, Pulmonary; Iloprost; Liver Cirrhosis; Liver Transplantation; Male; Treatment Failure; Vasodilator Agents

Portopulmonary hypertension (PPHTN) is a rare complication of liver cirrhosis. Prostanoids have been shown to be effective in the treatment of PPHTN and have been used as a bridge to orthotopic liver transplantation. However, inhibition of platelet aggregation might be a limitation of prostacyclin therapy in patients with end-stage liver disease having an increased risk of bleeding from esophageal varices. The effect of oral bosentan, a dual endothelin-receptor antagonist in the reversal of PPHTN, is still unclear. We report a case of PPHTN (mean pulmonary artery pressure [mPAP] of 51 mmHg) that was successfully switched from inhalative iloprost to oral bosentan therapy. Hemodynamic and symptomatic improvements were maintained after a 12-month long-term treatment with inhalative iloprost as well as after single oral bosentan therapy. This is the first reported case of a successful switch from therapy with an inhalative prostacyclin analogue to oral bosentan in a patient suffering from PPHTN. Thus, oral bosentan therapy might be a promising new option for patients suffering from PPHTN.

Topics: Administration, Inhalation; Administration, Oral; Antihypertensive Agents; Bosentan; Drug Therapy, Combination; Female; Follow-Up Studies; Hemodynamics; Humans; Hypertension, Portal; Hypertension, Pulmonary; Iloprost; Liver Cirrhosis; Liver Transplantation; Middle Aged; Platelet Aggregation Inhibitors; Sulfonamides; Time Factors

In the present experiment the pharmacokinetics of iloprost was studied in eight hospitalized patients suffering from liver cirrhosis (mean age: 56 years, 3 females, 5 males, child-classification: A [n = 1], B [n = 5], C [n = 2]/mean 14C-aminopyrine breath test: 3.9% dose/2 h). Iloprost was administered as a 1 h-i.v. infusion with 1 ng/kg/min to all the test subjects. Steady state plasma levels of 93 +/- 31 pg/ml were observed at the end of infusion. The terminal half-life of iloprost was 28 +/- 24 min. From AUC values of 126 +/- 60 pg.h/ml a total clearance of 10 +/- 5 ml/min/kg was calculated. The study demonstrated that iloprost clearance was reduced by a factor of 2 in patients suffering from hepatic dysfunction compared with healthy subjects. Individual dose titration is the recommended dose regimen for iloprost therapy in all patients. Therefore, apart from a reduction of the starting dose (of approximately 50%) for titration, special recommendations are not necessary for patients with impaired liver function.

Topics: Adult; Aged; Breath Tests; Female; Half-Life; Humans; Iloprost; Infusions, Intravenous; Liver Cirrhosis; Male; Metabolic Clearance Rate; Middle Aged; Time Factors