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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-␣) overproduction contributes to vasodilatation, which is improved by pentoxifylline, a TNF-␣ 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-␣ levels were evaluated. Adverse effects and tolerability were assessed. The 9 patients had a mean age of 55 Ϯ 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 ) ϭ 54 Ϯ 12 mm Hg, mean alveolar-arterial oxygen gradient (A-a PaO 2 ) ϭ 57 Ϯ 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 ϭ 0.3) or A-a PaO 2 (P ϭ 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][1200][1201][1202][1203] 2008 Hepatopulmonary syndrome (HPS) results from intrapulmonary microvascular dilatation that impairs arterial oxygenation in the setting of cirrhosis or portal hypertension. 1 As many as 10%-20% of patients with cirrhosis being evaluated for orthotopic liver transplantation (OLT) have advanced HPS, 2 and mortality is greater in those with HPS than in those without HPS. 3 Currently, OLT is the only effective treatment, although postoperative mortality in HPS is increased with respect to patients with cirrhosis without HPS, with a 1-year survival of 68% to 80%. 4 Therefore, effective medical therapy for advanced HPS could improve both preoperative and postoperative mortality.Recent work in experimental models of HPS has revealed that both nitric oxide synthase-derived nitric oxide and heme oxygenase-derived carbon monoxide cause intrapulmonary vasodilatation. These alterations appear to be driven in part by tumor necrosis factor alpha (TNF-␣) modulation of pulmonary blood flow and intravascular monocyte accumulation. 5-7 PentoxifyllineAbbreviations: A-a PaO 2 , alveolar-arterial oxygen gradient; ALT, alanine aminotransferase; AST, aspartate aminotransferase; HCV, hepatitis C virus; HPS, hepatopulmonary syndrome; INR, internat...

Chronic obstructive pulmonary disease (COPD) may cause significant symptoms and have an impact on survival. Smoking is an important risk factor for COPD and is common in candidates for liver transplantation; however, the risk factors for and outcomes of COPD in this population are unknown. We performed a prospective cohort study of 373 patients being evaluated for liver transplantation at 7 academic centers in the United States. COPD was characterized by expiratory airflow obstruction and defined as follows: prebronchodilator forced expiratory volume in 1 second/forced vital capacity Ͻ 0.70. Patients completed the Liver Disease Quality of Life Questionnaire 1.0, which included the Short Form-36. The mean age of the study sample was 53 Ϯ 9 years, and 234 (63%) were male. Sixty-seven patients (18%, 95% confidence interval 14%-22%) had COPD, and 224 (60%) had a history of smoking. Eighty percent of patients with airflow obstruction did not previously carry a diagnosis of COPD, and 27% were still actively smoking. Older age and any smoking (odds ratio ϭ 3.74, 95% confidence interval 1.94-7.23, P Ͻ 0.001) were independent risk factors for COPD. Patients with COPD had worse New York Heart Association functional class and lower physical component summary scores on the 36-Item Short Form but had short-term survival similar to that of patients without COPD. In conclusion, COPD is common and often undiagnosed in candidates for liver transplantation. Older age and smoking are significant risk factors of COPD, which has adverse consequences on functional status and quality of life in these patients.

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