Pharmacological Treatment for Hepatopulmonary Syndrome

Abstract

Aim. Hepatopulmonary syndrome is a pulmonary dysfunction in the context of liver cirrhosis characterized by arterial deoxygenation. Affected patients have increased morbidity and mortality, and many of them expire before undergoing liver transplantation. Therefore, finding medical therapy as a bridge to transplantation or as a final treatment is necessary. In this study, we aimed to review the current literature about pharmacological options available for treatment of hepatopulmonary syndrome. Methods. A PubMED and Scopus search was conducted in January 2013 on the English literature published in any time period to find human and animal studies reporting pharmacological therapy of hepatopulmonary syndrome. Results. Out of 451 studies, 29 relevant articles were included. The number of patients, type, dose, duration, and mechanism of drugs in these studies was extracted and summarized separately. Most of pharmacologic agents act through inhibition of nitric oxide synthase and reduction in nitric oxide production, inactivation of endothelin-1, and treatment of bacterial translocation and pulmonary angiogenesis. Conclusion. Several drugs have been applied for the treatment of HPS with conflicting results. However, no large randomized trial has been conducted probably due to low number of patients. Multicentered clinical trials are necessary to investigate these drugs.

Potential Clinical Targets in Hepatopulmonary Syndrome: Lessons From Experimental Models

“…Small human studies reporting on the use of L‐NAME, norfloxacin, and pentoxifylline, agents that have been proven effective in experimental HPS, had contradictory results (Table ) . Other drugs, including mycophenolate mofetil, paroxetine, iloprost, somatostatin, almitrine, and cyclooxygenase inhibitors, have been empirically tried in small studies and did not show a clear benefit . Improvement of gas exchange was documented in three studies in which HPS patients were treated with garlic, which has been reported to have antiangiogenic activity and is known to alter the gut microbiome, two components that are implicated in experimental HPS pathogenesis .…”

“…(63)(64)(65)(66)(67)(68)(69)(70) Other drugs, including mycophenolate mofetil, paroxetine, iloprost, somatostatin, almitrine, and cyclooxygenase inhibitors, have been empirically tried in small studies and did not show a clear benefit. (71) Improvement of gas exchange was documented in three studies in which HPS patients were treated with garlic, which has been reported to have antiangiogenic activity and is known to alter the gut microbiome, two components that are implicated in experimental HPS pathogenesis. (72)(73)(74) However, it is difficult to draw clinical conclusions from the small number of included patients.…”

Extracorporeal membrane oxygenation for post-transplant hypoxaemia following very severe hepatopulmonary syndrome

“…Vasodilatory strategies including inhaled nitric oxide, intravenous prostacyclin and inhaled prostaglandin4 5 were considered, but none of these were available to us at this time. Intravenous methylene blue is reportedly useful by its inhibition of nitric oxide synthase effect and inhibition of pulmonary angiogenesis6 but was not available to us. The oxygenation decreased further, and for want of other measures, a salvage ECMO was considered as a life-saving measure.…”

Hepatopulmonary Syndrome: A Brief Review

“…A number of methods have been tested to halt the progression of HPS. Nitric oxide inhalation, low consumption of L-arginine using methylene blue, aspirin, antibiotic usage to reduce intestines bacterial translocation, somatostatin, indomethacin, garlic, and transjugular intrahepatic portosystemic shunt (TIPS) have not shown any particular benefit as long-term treatment of HPS [1,2,21,22]. According to theory, the use of TIPS could reduce portal hypertension and improve oxygenation.…”