Pilot study of pentoxifylline in hepatopulmonary syndrome.

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-alpha) overproduction contributes to vasodilatation, which is improved by pentoxifylline, a TNF-alpha 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-alpha 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 (PaO(2)) = 54 +/- 12 mm Hg, mean alveolar-arterial oxygen gradient (A-a PaO(2)) = 57 +/- 15 mm Hg]. Of the 9 patients enrolled, follow-up blood gases were done in 7. There was no significant change in PaO(2) (P = 0.3) or A-a PaO(2) (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.

Utility of pulse oximetry screening for hepatopulmonary syndrome.

BACKGROUND & AIMS: Hepatopulmonary syndrome is characterized by oxygenation abnormalities caused by intrapulmonary vasodilatation in the setting of liver disease and/or portal hypertension. This syndrome occurs in approximately 15%-30% of cirrhotic patients and influences mortality and transplant candidacy. However, no specific screening guidelines are established. We evaluated pulse oximetry with contrast echocardiography in detecting hepatopulmonary syndrome in a cohort of patients undergoing evaluation for liver transplantation. METHODS: One hundred twenty-seven consecutive patients referred for liver transplantation evaluation were prospectively enrolled and underwent pulse oximetry, contrast echocardiography, and arterial blood gas measurements on room air. Demographic, clinical, and laboratory data were recorded and analyzed. RESULTS: Forty-one (32%) patients were found to have hepatopulmonary syndrome. There were no significant differences in demographic or clinical features compared with patients without hepatopulmonary syndrome, with the exception of pulse oximetry and oxygenation abnormalities. With a threshold value of <96%, pulse oximetry had a sensitivity and specificity of 100% and 88%, respectively, for detecting patients with a partial pressure of oxygen <60 mm Hg. Receiver operator characteristic analysis revealed that a pulse oximetry value of < or =94% detected all patients with a partial pressure of oxygen <60 mm Hg with an increased specificity of 93%. In addition, higher pulse oximetry thresholds reliably identified HPS patients with less severe hypoxemia, albeit with lower specificity. CONCLUSIONS: Pulse oximetry is a simple, low cost, and widely available technique that reliably predicts the presence and severity of hypoxemia in patients with hepatopulmonary syndrome. Institution of pulse oximetry screening might enhance detection and improve management of hepatopulmonary syndrome in cirrhosis.