Pilot study of pentoxifylline in hepatopulmonary syndrome
Open Access
- 30 July 2008
- journal article
- clinical trial
- Published by Ovid Technologies (Wolters Kluwer Health) in Liver Transplantation
- Vol. 14 (8), 1199-1203
- https://doi.org/10.1002/lt.21482
Abstract
Hepatopulmonary syndrome (HPS) results when chronic liver disease or portal hypertension causes intrapulmonary microvascular dilatation with hypoxemia. In experimental HPS, tumor necrosis factor alpha (TNF‐α) overproduction contributes to vasodilatation, which is improved by pentoxifylline, a TNF‐α inhibitor. The effectiveness of pentoxifylline in humans is unknown. The aim of this open‐label, single‐arm clinical trial was to assess the efficacy and tolerability of pentoxifylline in patients with cirrhosis and advanced HPS undergoing liver transplantation evaluation. Nine adults with cirrhosis and moderate to severe HPS were enrolled. All patients had an initial 2‐week titration to a target dose of pentoxifylline of 400 mg by mouth every 8 hours, which was continued for 6 weeks. Baseline and follow‐up arterial blood gases and TNF‐α levels were evaluated. Adverse effects and tolerability were assessed. The 9 patients had a mean age of 55 ± 10 years, and 67% were female. The most common causes of cirrhosis were hepatitis C virus and alcohol (55%). The mean Model for End‐Stage Liver Disease score was 11 (range, 6‐19), and patients had advanced hypoxemia [mean partial pressure of arterial oxygen (PaO2) = 54 ± 12 mm Hg, mean alveolar‐arterial oxygen gradient (A‐a PaO2) = 57 ± 15 mm Hg]. Of the 9 patients enrolled, follow‐up blood gases were done in 7. There was no significant change in PaO2 (P = 0.3) or A‐a PaO2 (P = 0.3) with treatment. Pentoxifylline was poorly tolerated. Nausea (100%) and vomiting (56%) were the predominant side effects, and only a single patient was able to complete full‐dose therapy. Treatment with pentoxifylline did not improve arterial oxygenation in advanced HPS, and tolerance was limited by gastrointestinal toxicity. Liver Transpl 14:1199–1203, 2008. © 2008 AASLD.Keywords
This publication has 15 references indexed in Scilit:
- Early switch to pentoxifylline in patients with severe alcoholic hepatitis is inefficient in non-responders to corticosteroidsJournal of Hepatology, 2008
- Prevention of hepatopulmonary syndrome and hyperdynamic state by pentoxifylline in cirrhotic rats.European Respiratory Journal, 2004
- A pilot study to investigate the use of oxpentifylline (pentoxifylline) and thalidomide in portal hypertension secondary to alcoholic cirrhosisAlimentary Pharmacology & Therapeutics, 2003
- Prevention of Gram-Negative Translocation Reduces the Severity of Hepatopulmonary SyndromeAmerican Journal of Respiratory and Critical Care Medicine, 2002
- Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: A double-blind, placebo-controlled trialGastroenterology, 2000
- The role of endothelial nitric oxide synthase in the pathogenesis of a rat model of hepatopulmonary syndromeGastroenterology, 1997
- THE HEPATOPULMONARY SYNDROME: Effect of Liver TransplantationClinics in Chest Medicine, 1996
- The Hepatopulmonary SyndromeAnnals of Internal Medicine, 1995
- Hepatopulmonary SyndromeSocial psychiatry. Sozialpsychiatrie. Psychiatrie sociale, 1993
- The hepatopulmonary syndrome: new name, old complexities.Thorax, 1992