LIVER TRANSPLANTATION 20:724–727, 2014
ORIGINAL ARTICLE
Long-Term Follow-Up of Portopulmonary Hypertension Patients After Liver Transplantation Saira Khaderi,1 Rashid Khan,2 Zeenath Safdar,1 Rise Stribling,1 John M. Vierling,1 John A. Goss,1 and Norman L. Sussman1 1 Baylor College of Medicine, Houston, TX; and 2Department of Gastroenterology, University of Texas Medical Branch at Galveston, Galveston, TX
Portopulmonary hypertension (POPH) occurs in 5.3% to 8.5% of patients with advanced liver disease. The rate of survival in the absence of orthotopic liver transplantation (OLT) is reportedly 38% at 3 years and 28% at 5 years. Moderate to severe POPH [mean pulmonary artery pressure (MPAP) 35 mm Hg] is associated with a perioperative mortality rate of 50%. Single-center series have demonstrated the feasibility and short-term efficacy of OLT after POPH is controlled with vasodilators, but long-term outcomes have not been reported. Our aim was to determine graft and patient survival rates and the effects of OLT on pulmonary hypertension (PHT) in patients undergoing transplantation for POPH at our center. Four hundred eighty-eight adult patients underwent transplantation between June 2004 and January 2011, and 7 underwent transplantation for POPH after their MPAP was reduced to 35 mm Hg with vasodilators. These 7 patients included 3 men and 4 women with ages ranging from 39 to 54 years at the time of OLT. All patients received IV EPO or inhaled EPO during the perioperative period, and all were weaned off EPO over the course of 3 days to 8 months. Both the graft and patient survival rates were 85.7% after a median follow-up of 7.8 years. One patient had recurrent hepatitis C virus cirrhosis and recurrent POPH and died from multiorgan failure unrelated to PHT. Four of the remaining 6 patients required oral vasodilator therapy for persistent PHT. Only 2 of the 7 patients (4.4 and 8.5 years after OLT) did not have PHT. In conclusion, patients with POPH responsive to vasodilator therapy may have excellent long-term graft and patient survival after OLT. Despite the alleviation of portal hypertension by OLT, most patients have persistent or recurrent PHT that can be controlled C 2014 AASLD. with oral vasodilators. Liver Transpl 20:724-727, 2014. V Received December 24, 2013; accepted March 7, 2014.
See Editorial on Page 635 Portopulmonary hypertension (POPH) is a syndrome of elevated pulmonary artery pressure in the setting of portal hypertension. POPH is defined hemodynamically as a mean pulmonary artery pressure (MPAP) 25 mm Hg, a pulmonary vascular resistance (PVR) 240 dynescm25, and a pulmonary occlusion (wedge) pressure 15 mm Hg,1 and it has been reported in 5.3% to 8.5% of patients with advanced
liver disease.2-4 Moderate POPH and severe POPH, defined as an MPAP 35 mm Hg and an MPAP 45 mm Hg, respectively, are less common, but they are more important as clinical entities. Survival for patients with moderate or severe POPH without orthotopic liver transplantation (OLT) is reportedly 38% at 3 years5 and 28% at 5 years,6 and the prognosis is worse than that for patients with uncomplicated cirrhosis or idiopathic pulmonary hypertension (PHT).5 POPH also affects survival after liver transplantation. Historical studies showed that mild POPH
Abbreviations: EPO, epoprostenol; IV, intravenous; MELD, Model for End-Stage Liver Disease; MPAP, mean pulmonary artery pressure; NYHA, New York Heart Association; OLT, orthotopic liver transplantation; PHT, pulmonary hypertension; POPH, portopulmonary hypertension; PVR, pulmonary vascular resistance. See Editorial on Page 635 Address reprint requests to Saira Khaderi, M.D., M.P.H., Division of Abdominal Transplantation, Baylor College of Medicine, 6620 Main Street, Suite 1450, Houston, TX 77030. Telephone: 832-355-1400; FAX: 713-610-2479; E-mail: [email protected] DOI 10.1002/lt.23870 View this article online at wileyonlinelibrary.com. LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
C 2014 American Association for the Study of Liver Diseases. V
LIVER TRANSPLANTATION, Vol. 20, No. 6, 2014
posed no additional mortality risk after OLT, but moderate disease was associated with a 50% perioperative mortality rate, and severe disease was universally fatal.7 Medical treatment for POPH improves survival in the absence of OLT, but the best outcomes are seen when medical treatment is followed by liver transplantation.8 We first reported successful liver transplantation after the medical management of moderate to severe POPH with intravenous (IV) epoprostenol (EPO) in 2006.9 MPAP was decreased to 50 mm Hg on an echocardiogram. These patients subsequently underwent right heart catheterization to confirm the diagnosis of POPH before the initiation of vasodilator therapy. The criteria for vasodilator therapy were an MPAP 35 mm Hg and a pulmonary capillary wedge pressure 15 mm Hg measured at the time of right heart catheterization. Other etiologies of PHT were excluded on the basis of a patient’s history, laboratory findings, and imaging. The study started in 2004 when prostanoids were the first-line therapy for POPH and the focus of therapy was entirely the MPAP. Over the course of the study, we have seen the introduction of a number of oral agents, and the focus of therapy has shifted from the MPAP to the transpulmonary pressure gradient and right ventricular function. All the patients in this study required EPO during the preoperative period, and all received inhaled and/or IV EPO during surgery and the immediate postoperative period. Pretransplant patients were seen regularly at a clinic for serial echocardiography, 6-minute walk tests, and confirmatory right heart catheterization when the echocardiogram showed an improved pulmonary artery pressure. EPO was titrated on the basis of the estimated pulmonary
KHADERI ET AL. 725
artery systolic pressure (echocardiogram) or the MPAP (right heart catheterization). We performed 488 adult liver transplants at our center between June 2004 and January 2011. Only 7 of these transplants (1.4%) were for patients with moderate to severe POPH. This study includes all 7 transplant patients. In all cases, OLT was performed after MPAP was decreased to 35 mm Hg with vasodilator therapy. Intraoperative transesophageal echocardiography was used in some cases to assist in the management of hemodynamics and cardiac function during surgery. Vasodilator therapy was tapered after transplantation; the New York Heart Association (NYHA) functional class, 6-minute walk tests, and echocardiogram estimates of the pulmonary artery systolic pressure were taken into account. Oral vasodilators were added while EPO was tapered in most cases. Patients underwent an echocardiogram and a 6-minute walk test every 3 to 6 months in the first year after transplantation.
RESULTS Seven patients with POPH received liver transplants at our center between 2004 and 2011 (Table 1). The patients included 3 men and 4 women with a mean age of 45 (range 5 39-54 years) at the time of OLT. Cirrhosis was secondary to hepatitis C in 3 patients, secondary to alcohol in 2 patients, and cryptogenic in 2 patients. Five patients had moderate POPH with MPAP values ranging from 37.7 to 43.3 mm Hg, and 2 had severe POPH with MPAP values of 50 and 55 mm Hg. Six patients received only IV EPO before transplantation, and 1 patient was managed with oral sildenafil. The IV EPO doses varied from 8 to 22 ng/kg/ minute, and the sildenafil doses varied from 20 to 40 mg every 8 hours. MPAP was 35 mm Hg for all patients at the time of liver transplantation. The duration of the pretransplant treatment ranged from 1 to 21 months. Each patient received automatic Model for End-Stage Liver Disease (MELD) exception points at the time of listing. The MELD score increased every 3 months as long as MPAP remained 35 mm Hg and PVR remained
ORIGINAL ARTICLE
Long-Term Follow-Up of Portopulmonary Hypertension Patients After Liver Transplantation Saira Khaderi,1 Rashid Khan,2 Zeenath Safdar,1 Rise Stribling,1 John M. Vierling,1 John A. Goss,1 and Norman L. Sussman1 1 Baylor College of Medicine, Houston, TX; and 2Department of Gastroenterology, University of Texas Medical Branch at Galveston, Galveston, TX
Portopulmonary hypertension (POPH) occurs in 5.3% to 8.5% of patients with advanced liver disease. The rate of survival in the absence of orthotopic liver transplantation (OLT) is reportedly 38% at 3 years and 28% at 5 years. Moderate to severe POPH [mean pulmonary artery pressure (MPAP) 35 mm Hg] is associated with a perioperative mortality rate of 50%. Single-center series have demonstrated the feasibility and short-term efficacy of OLT after POPH is controlled with vasodilators, but long-term outcomes have not been reported. Our aim was to determine graft and patient survival rates and the effects of OLT on pulmonary hypertension (PHT) in patients undergoing transplantation for POPH at our center. Four hundred eighty-eight adult patients underwent transplantation between June 2004 and January 2011, and 7 underwent transplantation for POPH after their MPAP was reduced to 35 mm Hg with vasodilators. These 7 patients included 3 men and 4 women with ages ranging from 39 to 54 years at the time of OLT. All patients received IV EPO or inhaled EPO during the perioperative period, and all were weaned off EPO over the course of 3 days to 8 months. Both the graft and patient survival rates were 85.7% after a median follow-up of 7.8 years. One patient had recurrent hepatitis C virus cirrhosis and recurrent POPH and died from multiorgan failure unrelated to PHT. Four of the remaining 6 patients required oral vasodilator therapy for persistent PHT. Only 2 of the 7 patients (4.4 and 8.5 years after OLT) did not have PHT. In conclusion, patients with POPH responsive to vasodilator therapy may have excellent long-term graft and patient survival after OLT. Despite the alleviation of portal hypertension by OLT, most patients have persistent or recurrent PHT that can be controlled C 2014 AASLD. with oral vasodilators. Liver Transpl 20:724-727, 2014. V Received December 24, 2013; accepted March 7, 2014.
See Editorial on Page 635 Portopulmonary hypertension (POPH) is a syndrome of elevated pulmonary artery pressure in the setting of portal hypertension. POPH is defined hemodynamically as a mean pulmonary artery pressure (MPAP) 25 mm Hg, a pulmonary vascular resistance (PVR) 240 dynescm25, and a pulmonary occlusion (wedge) pressure 15 mm Hg,1 and it has been reported in 5.3% to 8.5% of patients with advanced
liver disease.2-4 Moderate POPH and severe POPH, defined as an MPAP 35 mm Hg and an MPAP 45 mm Hg, respectively, are less common, but they are more important as clinical entities. Survival for patients with moderate or severe POPH without orthotopic liver transplantation (OLT) is reportedly 38% at 3 years5 and 28% at 5 years,6 and the prognosis is worse than that for patients with uncomplicated cirrhosis or idiopathic pulmonary hypertension (PHT).5 POPH also affects survival after liver transplantation. Historical studies showed that mild POPH
Abbreviations: EPO, epoprostenol; IV, intravenous; MELD, Model for End-Stage Liver Disease; MPAP, mean pulmonary artery pressure; NYHA, New York Heart Association; OLT, orthotopic liver transplantation; PHT, pulmonary hypertension; POPH, portopulmonary hypertension; PVR, pulmonary vascular resistance. See Editorial on Page 635 Address reprint requests to Saira Khaderi, M.D., M.P.H., Division of Abdominal Transplantation, Baylor College of Medicine, 6620 Main Street, Suite 1450, Houston, TX 77030. Telephone: 832-355-1400; FAX: 713-610-2479; E-mail: [email protected] DOI 10.1002/lt.23870 View this article online at wileyonlinelibrary.com. LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
C 2014 American Association for the Study of Liver Diseases. V
LIVER TRANSPLANTATION, Vol. 20, No. 6, 2014
posed no additional mortality risk after OLT, but moderate disease was associated with a 50% perioperative mortality rate, and severe disease was universally fatal.7 Medical treatment for POPH improves survival in the absence of OLT, but the best outcomes are seen when medical treatment is followed by liver transplantation.8 We first reported successful liver transplantation after the medical management of moderate to severe POPH with intravenous (IV) epoprostenol (EPO) in 2006.9 MPAP was decreased to 50 mm Hg on an echocardiogram. These patients subsequently underwent right heart catheterization to confirm the diagnosis of POPH before the initiation of vasodilator therapy. The criteria for vasodilator therapy were an MPAP 35 mm Hg and a pulmonary capillary wedge pressure 15 mm Hg measured at the time of right heart catheterization. Other etiologies of PHT were excluded on the basis of a patient’s history, laboratory findings, and imaging. The study started in 2004 when prostanoids were the first-line therapy for POPH and the focus of therapy was entirely the MPAP. Over the course of the study, we have seen the introduction of a number of oral agents, and the focus of therapy has shifted from the MPAP to the transpulmonary pressure gradient and right ventricular function. All the patients in this study required EPO during the preoperative period, and all received inhaled and/or IV EPO during surgery and the immediate postoperative period. Pretransplant patients were seen regularly at a clinic for serial echocardiography, 6-minute walk tests, and confirmatory right heart catheterization when the echocardiogram showed an improved pulmonary artery pressure. EPO was titrated on the basis of the estimated pulmonary
KHADERI ET AL. 725
artery systolic pressure (echocardiogram) or the MPAP (right heart catheterization). We performed 488 adult liver transplants at our center between June 2004 and January 2011. Only 7 of these transplants (1.4%) were for patients with moderate to severe POPH. This study includes all 7 transplant patients. In all cases, OLT was performed after MPAP was decreased to 35 mm Hg with vasodilator therapy. Intraoperative transesophageal echocardiography was used in some cases to assist in the management of hemodynamics and cardiac function during surgery. Vasodilator therapy was tapered after transplantation; the New York Heart Association (NYHA) functional class, 6-minute walk tests, and echocardiogram estimates of the pulmonary artery systolic pressure were taken into account. Oral vasodilators were added while EPO was tapered in most cases. Patients underwent an echocardiogram and a 6-minute walk test every 3 to 6 months in the first year after transplantation.
RESULTS Seven patients with POPH received liver transplants at our center between 2004 and 2011 (Table 1). The patients included 3 men and 4 women with a mean age of 45 (range 5 39-54 years) at the time of OLT. Cirrhosis was secondary to hepatitis C in 3 patients, secondary to alcohol in 2 patients, and cryptogenic in 2 patients. Five patients had moderate POPH with MPAP values ranging from 37.7 to 43.3 mm Hg, and 2 had severe POPH with MPAP values of 50 and 55 mm Hg. Six patients received only IV EPO before transplantation, and 1 patient was managed with oral sildenafil. The IV EPO doses varied from 8 to 22 ng/kg/ minute, and the sildenafil doses varied from 20 to 40 mg every 8 hours. MPAP was 35 mm Hg for all patients at the time of liver transplantation. The duration of the pretransplant treatment ranged from 1 to 21 months. Each patient received automatic Model for End-Stage Liver Disease (MELD) exception points at the time of listing. The MELD score increased every 3 months as long as MPAP remained 35 mm Hg and PVR remained
