Portal de Periódicos da CAPES

Model for end-stage liver disease (MELD) exception for portopulmonary hypertension

2006; Lippincott Williams & Wilkins; Volume: 12; Issue: S3 Linguagem: Inglês

10.1002/lt.20975

1527-6473

Michael J. Krowka, Michael B. Fallon, David C. Mulligan, Robert G. Gish,

Organ Transplantation Techniques and Outcomes

Patients with liver disease are predisposed to pulmonary arterial changes indistinguishable from those seen in idiopathic pulmonary artery hypertension. The effects of this abnormal liver-lung association, portopulmonary hypertension (POPH), on liver transplant waitlist mortality and patient outcome are not well understood, causing much debate over the appropriate allocation algorithms and the need for additional model for end-stage liver disease (MELD) score points.1 Early results of liver transplantation (LT) in patients with significant POPH were poor.2 It was not until later, in small, single-center experiences, that successful cases resulted in improved pulmonary vascular parameters post-LT.3 Recently, specific transthoracic Doppler echocardiogram screening, hemodynamic diagnostic criteria, and management recommendations for POPH have been proposed by the European Respiratory Society Task Force on pulmonary-hepatic vascular disorders.4 The diagnosis of POPH is confirmed by right heart catheterization criteria that include measurements of mean pulmonary artery pressure (MPAP), pulmonary artery occlusion pressure (PAOP; also known as pulmonary capillary wedge pressure) cardiac output, and calculated pulmonary vascular resistance (PVR).4 Recent data suggest that PAOP criteria may need to be modified to allow patients with increased PAOP plus increased PVR to be diagnosed with POPH.5 In the era prior to the availability of LT and prostacyclin therapy, mean survival following diagnosis of POPH was 15 months, with half of the deaths related to pulmonary hypertension.6 In the current era, LT for POPH has resulted in intraoperative death and increased transplant hospitalization mortality.2, 3 A literature review (n = 43; 18 peer-reviewed studies)2 and a multicenter, prospective analysis (n = 66; 10 centers)3 indicated that a preoperative MPAP >35 mm Hg serves as a threshold for increased risk of death following LT. Notably, the literature review revealed that the diagnosis of POPH was initially made in the operating room in 65% of patients who underwent surgery for LT.2 Mortality was significant, with 10 of 14 deaths occurring within 21 days of LT; 3 deaths occurred intraoperatively. All deaths were associated with a MPAP >35 mm Hg pre-LT. Of 29 survivors, 15 had MPAP >35 mm Hg, but 12 had PVR 35 mm Hg). Prostacyclin therapy was given to 5 of 23 survivors (18/23 had MPAP >35 mm Hg), and 62% had PVR 35 mm Hg and PVR >400 dynes/sec/cm−5). Despite poor outcomes before and after LT, the persistence of POPH, and the de novo development of pulmonary artery hypertension after LT, there are many reports of improvement in POPH after LT.7-14 These case reports and small series suggest that pre-LT treatment and hemodynamic improvement may confer a long-term survival advantage post-LT. In the largest and most recent series (n = 22), the 5-year survival rate for patients with POPH undergoing LT was 64% (47 % had pre-LT prostacyclin). Additional experience is needed to confirm that pre-LT treatment response using prostacyclin analogues and/or other agents results in improved LT survival and pulmonary hemodynamics.15 Reported experiences have yet to address whether patients with POPH are at a higher risk of death while awaiting LT compared with other patients with the same degree of liver dysfunction. However, patients with POPH who do not undergo LT (25/66 died while on the waiting list and 41 were denied LT) have a 5-year survival rate of approximately 30%.15 Finally, it is likely that right heart function plays an important role in patient outcome. Therefore, methods and criteria pertaining to right heart function need to evolve from data collection. POPH, portopulmonary hypertension; MELD, model for end-stage liver disease; LT, liver transplantation; MPAP, mean pulmonary artery pressure; PVR, pulmonary vascular resistance. MELD scores correlate poorly with the severity of POPH.5 There is limited evidence to support additional priority for highly selected patients with POPH based on selected right heart catheterization pulmonary hemodynamic data (MPAP and PVR). The rationale for such an approach is to prevent progression of pulmonary hemodynamic abnormality and subsequent irreversible pulmonary hypertension, eventually resulting in right heart failure and death. MELD exception should be based on data that are standardized and serially collected for pre- and post-LT outcomes. Future priority will depend on analysis of such standardized data. This data collection can occur through the existing National Institutes of Health–supported framework of the study group for Pulmonary Vascular Complications of Liver Disease.16 Portal hypertension (clinical or hemodynamic diagnosis) Right heart catheterization criteria ▪ MPAP >25 mm Hg ▪ PVR >240 dynes/sec/cm−5 ▪ Transpulmonary gradient >12 mm Hg When transpulmonary gradient = MPAP-PAOP; this modified criterion4, 5 adjusts for cases in which PAOP may be increased due to excess central volume. POPH exists with severity characterized by MPAP >35 mm Hg A minimum of 12 weeks of U.S. Food and Drug Administration–approved pulmonary arterial hypertension therapy results in the following pulmonary hemodynamic profile: • MPAP <35 mm Hg and PVR <400 dynes/sec/cm−5 • Satisfactory right ventricular function exists (center-specific testing) Patients who do not undergo LT within 6 months may be granted additional MELD exception points after a review by the regional review boards. Liver transplantation outcome data will be reviewed every 12 months prior to extending MELD exception to other POPH hemodynamic profiles.