0041-1337/03/7905-1482/0 TRANSPLANTATION Vol. 79, 1482–1489, No. 5, May 15, 2003 Copyright © 2003 by Lippincott Williams & Wilkins, Inc. Printed in U.S.A. LIVER TRANSPLANTATION FOR HEPATOPULMONARY SYNDROME: A TEN-YEAR EXPERIENCE IN PARIS, FRANCE CAMILLE TAILL ´ E, 1 JACQUES CADRANEL, 2 AGN ` ES BELLOCQ, 2 GABRIEL THABUT, 1 OLIVIER SOUBRANE, 3 FRANC ¸ OIS DURAND, 1 PHILIPPE ICHA ¨ I, 4 CHRISTOPHE DUVOUX, 5 JACQUES BELGHITI, 1 YVON CALMUS, 3 AND HERV ´ E MAL 1,6 Background. Although the possibility of reversing hepatopulmonary syndrome (HPS) after liver trans- plantation is now well established, the proportion of patients in whom reversibility is observed and the time to resolution of HPS remain uncertain. Methods. We analyzed the outcome of all adult pa- tients with HPS who underwent orthotopic liver transplantation in all the liver transplant centers in Paris, during a 10-year period. Results. Twenty-three adult patients (median age, 47 years; range, 14 – 64) underwent transplantation in four institutions. Median PaO 2 was 52 (range, 32– 67) mm Hg and median alveolar-arterial oxygen gradient was 66 mm Hg. When patients were breathing 100% O 2 , median PaO 2 was 310 (range, 74 – 663) mm Hg. Median isotopic shunt ratio was 33% (range, 0 – 80%). The over- all mortality during the study period was 30.5% (7/23). Perioperative mortality was 8.5%, whereas late mor- tality was 22%. None of the preoperative characteris- tics of HPS (isotopic shunt ratio, PaO 2 on room air or on 100% oxygen) was associated with overall postop- erative mortality. Of the 21 patients surviving the perioperative period (median follow-up, 17 months; range, 0.5–72), a decrease in alveolar-arterial oxygen gradient of at least 5 mm Hg and at least 10 mm Hg was observed in 21 of 21 and in 18 of 21 patients, respec- tively, with great variations in the time of improve- ment. The threshold of 70 mm Hg was reached in 15 patients. The lower the preoperative PaO 2 , the longer the time to reach this point. Conclusion. Our data strongly support the role of orthotopic liver transplantation in adult patients with HPS, regardless of its severity. Hepatopulmonary syndrome (HPS) is defined as a triad of liver disease, increased alveolar-arterial oxygen gradient [P(A-a)O 2 ] on room air (RA), and evidence of intrapulmonary vascular dilatation (1). This complication was initially con- sidered a contraindication for liver transplantation when severe debilitating hypoxemia was present because of an expected increase in early postoperative mortality and un- certainties concerning long-term outcome. However, several case reports have subsequently demonstrated that even in severe cases, hypoxemia could reverse after transplantation. As a result, most centers currently consider that HPS repre- sents an indication for liver transplantation per se, whatever the severity of the underlying liver disease (2). However, data on the proportion of patients in whom HPS reversibility is observed and on the resolution delay, especially in patients with severe preoperative hypoxemia, remain poorly defined. Moreover, predictors of mortality and reversibility have been proposed (3) but have not been confirmed. The aim of this retrospective multicenter study was to address these issues by analyzing the outcome of all adult patients with HPS who underwent orthotopic liver transplantation (OLT) in all Pa- risian transplant centers during a 10-year period, with spe- cial emphasis on morbidity and mortality of OLT in this setting, prevalence of reversal of HPS, and time to improve- ment of gas exchange. PATIENTS AND METHODS In December 2000, the medical director of each of the six adult liver transplantation centers of the “Assistance Publique–Ho ˆpitaux de Paris,” was contacted to collect all cases of patients with HPS who underwent OLT from January 1991 to December 2000. Diagnostic of HPS was established in patients with chronic liver disease present- ing with PaO 2 less than 70 mm Hg or P(A-a)O 2 more than 20 mm Hg on RA and with delayed (more than three cardiac cycles) positive contrast-enhanced echocardiography (4). The medical charts of all patients who fulfilled the selection criteria were analyzed retrospec- tively by one of us (C.T.). No patient was excluded from analysis. Collection of Preoperative HPS Characteristics We collected preoperative values of arterial blood gases (ABG) at rest and in a supine position on RA and in response to 100% O 2 . P(A-a)O 2 was calculated using the measured PaO 2 and PaCO 2 and alveolar oxygen tension calculated from the alveolar gas equation assuming a standard respiratory exchange ratio of 0.8. Oximetric shunt ratio (OSR) was estimated during 100% O 2 breathing and was based on an assumed arteriovenous oxygen content difference of 5 mL/dL (5). Isotopic shunt ratio (ISR) was also assessed by 99m Tc-macroaggre- gated albumin perfusion lung scan in 19 patients. The amount of radioactivity was measured over the lungs and, according to the centers, over kidneys, brain, or the whole body using a scintillation camera. The ratio of systemic to total body activity (lungs and sys- temic) is an estimate of the magnitude of the shunt fraction. Shunt fraction was considered significant if greater than 6%, regardless of the technique (6). ISR was calculated from the radioactivity mea- sured over the brain, kidneys, or brain and kidneys in 11, 1, and 7 patients, respectively, assuming that the cerebral and renal circula- tion receive approximately 13% and 25% of the cardiac output in the resting state, respectively (6,7). 1 Service de Pneumologie et de R ´ eanimation Respiratoire et IN- SERM U408, Service d’H ´ epatologie, Service de Chirurgie Digestive, Ho ˆpital Beaujon, Clichy, France. 2 Service de Pneumologie et de R ´ eanimation Respiratoire, Service d’Explorations Fonctionnelles, Ho ˆpital Tenon, Paris, France. 3 Service de Chirurgie Digestive, Ho ˆpital Cochin, Paris, France. 4 Centre H ´ epato-Biliaire, Ho ˆpital Paul Brousse, Villejuif, France. 5 Service d’H ´ epatologie, Ho ˆpital Henri Mondor, Cr ´ eteil, France. 6 Address correspondence to: Herv ´ e Mal, M.D., Service de Pneumologie et de R ´ eanimation Respiratoire, Ho ˆpital Beaujon, 100 avenue du G ´ en ´ eral Leclerc, 92110, Clichy, France. E-mail: herve.mal@bjn.ap-hop-paris.fr. Received 14 June 2002. Revision Requested 17 July 2002. Accepted 8 January 2003. 1482 DOI: 10.1097/01.TP.0000061612.78954.6C