Journal of Gastroenterology and Hepatology (2002) 17, S253–S255 Blackwell Science, LtdOxford, UK JGHJournal of Gastroenterology and Hepatology0815-93192002 Blackwell Publishing Asia Pty Ltd 17Suppl.September 2002 25 PPH and HPS PS Kamath 10.1046/j.0815-9319.2002.00025.x Original ArticleS253S255BEES SGML Correspondence: Dr Patrick S Kamath, Professor of Medicine, Mayo Medical School, Consultant in Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Email: kamath.patrick@mayo.edu © 2002 Blackwell Publishing Asia Pty Ltd CONFERENCE PROCEEDINGS Portopulmonary hypertension and hepatopulmonary syndrome PATRICK S KAMATH Mayo Medical School, Mayo Clinic, Rochester, Minnesota, USA INTRODUCTION The pulmonary manifestations of liver disease include hypoxia related to ascites, hepatic hydrothorax with compressive atelectasis, 1 aspiration pneumonia second- ary to altered consciousness, portopulmonary hyper- tension, and hepatopulmonary syndrome. In addition, it is recognized that there is a significant history of smoking in many patients, especially with alcoholic liver disease and hepatitis C-related cirrhosis. 2 A few patients with alpha-1-antitrypsin deficiency-related cirrhosis also have lung disease. This review focuses on the pul- monary vascular syndromes accompanying cirrhosis of the liver, namely hepatopulmonary syndrome and por- topulmonary hypertension. In hepatopulmonary syndrome, patients present with hypoxia secondary to intrapulmonary vasodilatation. In portopulmonary hypertension, there is increased pul- monary vascular resistance. The pathophysiology of these two conditions is not certain. It appears that there is an imbalance in the pulmonary circulation between vasodilators such as nitric oxide and the prostanoids, and vasoconstrictors such as endothelins. 3 In hepatop- ulmonary syndrome, there is excessive nitric oxide (NO), 4 while in hepatopulmonary syndrome there may be excessive endothelin. These vasoactive substances normally do not enter the pulmonary circulation in sig- nificant amounts since they are cleared by the normal liver. However, if there is excessive production of these vasoactive substances from the splanchnic circulation, or by the cirrhotic liver, they may find their way into the pulmonary circulation, which ultimately results in the pulmonary vascular syndromes. HEPATOPULMONARY SYNDROME Hepatopulmonary syndrome is characterized by chronic liver disease, arterial hypoxemia, and intrapul- monary vascular dilatation. 5 The vascular abnormalities within the lung include either diffuse pulmonary vasodi- latation (type I hepatopulmonary syndrome) resulting in ventilation perfusion mismatch, or macroscopic ana- tomic shunting, which is present when there are discrete arteriovenous communications (type II hepatopulmo- nary syndrome). While a Pa0 2 of < 70% is usually required to make the diagnosis while patients are breathing room air, there can be near normalization of the Pa0 2 while breathing 100% oxygen in many patients. When a patient has hypoxemia in chronic liver dis- ease, the diagnosis of hepatopulmonary syndrome can be made if pulmonary vasodilatation and, thus, func- tional shunting can be demonstrated. This can be by means of echocardiography using agitated saline injected intravenously. In the presence of intracardiac right to left shunts, bubbles are seen in the left heart within the first three cardiac cycles. In hepatopulmo- nary syndrome, the bubbles are seen in the left heart after the third heart beat, usually between the third and sixth heart beat. 99m Technetium macroaggregated albu- min (MAA) permits quantification of the degree of intrapulmonary shunting. 6 Normally, less than 5% of the isotope can be quantitated over the brain. In hepatopulmonary syndrome, there is > 6% uptake in the brain. Pulmonary angiography is carried out in patients who have a poor response to 100% oxygen, demon- strated by an increase in the Pa0 2 to < 300 mmHg. In these patients, anatomic shunting is likely to be present (type II hepatopulmonary syndrome) and coil embo- lization of the arteriovenous shunts can be carried out through interventional radiology. Medical therapy of hepatopulmonary syndrome has been disappointing. Patients are advised oxygen supple- mentation. While therapy such as garlic and nitric oxide (NO) inhalation has been suggested, they have generally been disappointing. Ligation of portosystemic shunts, as well as cavoplasty in a patient with Budd–Chiari syn- drome have resulted in reversal of hepatopulmonary syndrome. In others, liver transplantation is recom- mended. The mortality with liver transplantation is high and ranges between 15 and 30% mortality at 1 year. Mortality is highest in patients in whom the pretrans- plant Pa0 2 is < 50 mmHg, and the brain uptake on 99m Tc MAA lung perfusion scans is > 30%.