Portopulmonary Hypertension

Abstract

Portopulmonary hypertension (POPH) refers to the presence of pulmonary arterial hypertension (PAH) in patients with portal hypertension. Pulmonary hypertension in patients with liver disease or portal hypertension can be due to multiple mechanisms, including hyperdynamic (high-flow) state, increased pulmonary venous congestion, and vascular constriction or obstruction of the pulmonary arterial bed. Vascular obstruction to pulmonary arterial flow, reflected by increased pulmonary vascular resistance (PVR), is a key parameter that defines POPH. Among patients with portal hypertension, reported incidence rates of POPH range from 2 to 9%. Long-term survival in cases of POPH is poor. Favorable responses to pulmonary vasodilator/vasomodulatory therapy have been observed, but prospective, randomized trials are lacking. Severe POPH with right ventricular failure despite vasodilator therapy is associated with poor outcomes in the setting of liver transplantation (LT) and is considered a contraindication to LT. The post-LT course of patients with moderate POPH is unpredictable, but most patients can be weaned from PAH-specific therapy over time.

Keywords

portopulmonary hypertension - pulmonary hypertension - portal hypertension - liver transplant

• References

• 1 Rodríguez-Roisin R, Krowka MJ, Hervé P, Fallon MB ; ERS Task Force Pulmonary-Hepatic Vascular Disorders (PHD) Scientific Committee. Pulmonary-hepatic vascular disorders (PHD). Eur Respir J 2004; 24 (5) 861-880
• 2 Stauber RE, Olschewski H. Portopulmonary hypertension: short review. Eur J Gastroenterol Hepatol 2010; 22 (4) 385-390
• 3 Simonneau G, Robbins IM, Beghetti M , et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2009; 54 (1, Suppl) S43-S54
• 4 Krowka MJ, Swanson KL, Frantz RP, McGoon MD, Wiesner RH. Portopulmonary hypertension: results from a 10-year screening algorithm. Hepatology 2006; 44 (6) 1502-1510
• 5 Hadengue A, Benhayoun MK, Lebrec D, Benhamou JP. Pulmonary hypertension complicating portal hypertension: prevalence and relation to splanchnic hemodynamics. Gastroenterology 1991; 100 (2) 520-528
• 6 Kawut SM, Krowka MJ, Trotter JF , et al; Pulmonary Vascular Complications of Liver Disease Study Group. Clinical risk factors for portopulmonary hypertension. Hepatology 2008; 48 (1) 196-203
• 7 Ramsay MAE, Simpson BR, Nguyen AT, Ramsay KJ, East C, Klintmalm GB. Severe pulmonary hypertension in liver transplant candidates. Liver Transpl Surg 1997; 3 (5) 494-500
• 8 Humbert M, Sitbon O, Chaouat A , et al. Pulmonary arterial hypertension in France: results from a national registry. Am J Respir Crit Care Med 2006; 173 (9) 1023-1030
• 9 Krowka MJ, Miller DP, Barst RJ , et al. Portopulmonary hypertension: a report from the US-based REVEAL Registry. In press
• 10 Condino AA, Ivy DD, O’Connor JA , et al. Portopulmonary hypertension in pediatric patients. J Pediatr 2005; 147 (1) 20-26
• 11 Whitworth JR, Sokol RJ. Hepato-portopulmonary disorders—not just in adults!. J Pediatr Gastroenterol Nutr 2005; 41 (4) 393-395
• 12 Talwaker JA, Swanson KL, Krowka MJ, Andrews JC, Kamath PS. Prevalence of spontaneous portosystemic shunts in patients with portopulmonary hypertension and effect on treatment. Gastroenterology 2011; 141 (5) 1673-1679
• 13 Mantz Jr FA, Craige E. Portal axis thrombosis with spontaneous portacaval shunt and resistant cor pulmonale. AMA Arch Pathol 1951; 52: 401-409
• 14 Naeye RL. “Primary” pulmonary hypertension with coexisting portal hypertension: a retrospective study of six cases. Circulation 1960; 22: 376-384
• 15 Senior RM, Britton RC, Turino GM, Wood JA, Langer GA, Fishman AP. Pulmonary hypertension associated with cirrhosis of the liver and with portacaval shunts. Circulation 1968; 37 (1) 88-96
• 16 Lebrec D, Capron JP, Dhumeaux D, Benhamou JP. Pulmonary hypertension complicating portal hypertension. Am Rev Respir Dis 1979; 120 (4) 849-856
• 17 Edwards BS, Weir EK, Edwards WD, Ludwig J, Dykoski RK, Edwards JE. Coexistent pulmonary and portal hypertension: morphologic and clinical features. J Am Coll Cardiol 1987; 10 (6) 1233-1238
• 18 Sankey EA, Crow J, Mallett SV , et al. Pulmonary platelet aggregates: possible cause of sudden perioperative death in adults undergoing liver transplantation. J Clin Pathol 1993; 46 (3) 222-227
• 19 Lockhart A. Pulmonary artery hypertension in portal hypertension. Gastroenterology 1985; 14: 123-138
• 20 Roberts KE, Fallon MB, Krowka MJ , et al; Pulmonary Vascular Complications of Liver Disease Study Group. Genetic risk factors for portopulmonary hypertension in patients with advanced liver disease. Am J Respir Crit Care Med 2009; 179 (9) 835-842
• 21 Tuder RM, Cool CD, Geraci MW , et al. Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am J Respir Crit Care Med 1999; 159 (6) 1925-1932
• 22 Benjaminov FS, Prentice M, Sniderman KW, Siu S, Liu P, Wong F. Portopulmonary hypertension in decompensated cirrhosis with refractory ascites. Gut 2003; 52 (9) 1355-1362
• 23 Pellicelli AM, Barbaro G, Puoti C , et al. Plasma cytokines and portopulmonary hypertension in patients with cirrhosis waiting for orthotopic liver transplantation. Angiology 2010; 61 (8) 802-806
• 24 Swanson KL, Wiesner RH, Nyberg SL, Rosen CB, Krowka MJ. Survival in portopulmonary hypertension: Mayo Clinic experience categorized by treatment subgroups. Am J Transplant 2008; 8 (11) 2445-2453
• 25 Robalino BD, Moodie DS. Association between primary pulmonary hypertension and portal hypertension: analysis of its pathophysiology and clinical, laboratory and hemodynamic manifestations. J Am Coll Cardiol 1991; 17 (2) 492-498
• 26 Le Pavec J, Souza R, Herve P , et al. Portopulmonary hypertension: survival and prognostic factors. Am J Respir Crit Care Med 2008; 178 (6) 637-643
• 27 Kawut SM, Taichman DB, Ahya VN , et al. Hemodynamics and survival of patients with portopulmonary hypertension. Liver Transpl 2005; 11 (9) 1107-1111
• 28 Hoeper MM, Seyfarth HJ, Hoeffken G , et al. Experience with inhaled iloprost and bosentan in portopulmonary hypertension. Eur Respir J 2007; 30 (6) 1096-1102
• 29 Cartin-Ceba R, Swanson KL, Iyer V, Wiesner RH, Krowka MJ. Safety and efficacy of ambrisentan for the treatment of portopulmonary hypertension. Chest 2011; 139 (1) 109-114
• 30 Reichenberger F, Voswinckel R, Steveling E , et al. Sildenafil treatment for portopulmonary hypertension. Eur Respir J 2006; 28 (3) 563-567
• 31 Hemmes AR, Robbins IM. Sildenafil monotherapy in portopulmonary hypertension can facilitate liver transplantation. Liver Transpl 2009; 15 (1) 15-19
• 32 Gough MS, White RJ. Sildenafil therapy is associated with improved hemodynamics in liver transplantation candidates with pulmonary arterial hypertension. Liver Transpl 2009; 15 (1) 30-36
• 33 Kuo PC, Johnson LB, Plotkin JS, Howell CD, Bartlett ST, Rubin LJ. Continuous intravenous infusion of epoprostenol for the treatment of portopulmonary hypertension. Transplantation 1997; 63 (4) 604-606
• 34 Krowka MJ, Frantz RP, McGoon MD, Severson C, Plevak DJ, Wiesner RH. Improvement in pulmonary hemodynamics during intravenous epoprostenol (prostacyclin): a study of 15 patients with moderate to severe portopulmonary hypertension. Hepatology 1999; 30 (3) 641-648
• 35 Sussman N, Kaza V, Barshes N , et al. Successful liver transplantation following medical management of portopulmonary hypertension: a single-center series. Am J Transplant 2006; 6 (9) 2177-2182
• 36 Ashfaq M, Chinnakotla S, Rogers L , et al. The impact of treatment of portopulmonary hypertension on survival following liver transplantation. Am J Transplant 2007; 7 (5) 1258-1264
• 37 Fix OK, Bass NM, De Marco T, Merriman RB. Long-term follow-up of portopulmonary hypertension: effect of treatment with epoprostenol. Liver Transpl 2007; 13 (6) 875-885
• 38 Sakai T, Planinsic RM, Mathier MA, de Vera ME, Venkataramanan R. Initial experience using continuous intravenous treprostinil to manage pulmonary arterial hypertension in patients with end-stage liver disease. Transpl Int 2009; 22 (5) 554-561
• 39 Melgosa MT, Ricci GL, García-Pagan JC , et al. Acute and long-term effects of inhaled iloprost in portopulmonary hypertension. Liver Transpl 2010; 16 (3) 348-356
• 40 Krowka MJ, Plevak DJ, Findlay JY, Rosen CB, Wiesner RH, Krom RA. Pulmonary hemodynamics and perioperative cardiopulmonary-related mortality in patients with portopulmonary hypertension undergoing liver transplantation. Liver Transpl 2000; 6 (4) 443-450
• 41 Krowka MJ, Mandell MS, Ramsay MA , et al. Hepatopulmonary syndrome and portopulmonary hypertension: a report of the multicenter liver transplant database. Liver Transpl 2004; 10 (2) 174-182
• 42 Murray KF, Carithers Jr RL ; AASLD. AASLD practice guidelines: evaluation of the patient for liver transplantation. Hepatology 2005; 41 (6) 1407-1432
• 43 Ramsay M. Portopulmonary hypertension and right heart failure in patients with cirrhosis. Curr Opin Anaesthesiol 2010; 23 (2) 145-150
• 44 Fukazawa K, Pretto Jr. EA. Poor outcome following aborted orthotopic liver transplantation due to severe porto-pulmonary hypertension. J Hepatobiliary Pancreat Sci 2010; 17 (4) 505-508
• 45 Castro M, Krowka MJ, Schroeder DR , et al. Frequency and clinical implications of increased pulmonary artery pressures in liver transplant patients. Mayo Clin Proc 1996; 71 (6) 543-551
• 46 DePeitri L, Montalti R, Begliomini B , et al. Pulmonary hypertension as a predictor of postoperative complications and mortality after liver transplantation. Transplant Proc 2010; 42 (4) 1188-1190
• 47 Tapper EB, Knowles D, Heffron T, Lawrence EC, Csete M. Portopulmonary hypertension: imatinib as a novel treatment and the Emory experience with this condition. Trans Proc 2009; 41 (5) 1969-1971
• 48 Krowka MJ, Fallon MB, Mulligan DC, Gish RG. Model for end-stage liver disease (MELD) exception for portopulmonary hypertension. Liver Transpl 2006; 12 (Suppl 3) S114-S116
• 49 Bandara M, Gordon FD, Sarwar A , et al. Successful outcomes following living donor liver transplantation for portopulmonary hypertension. Liver Transpl 2010; 16 (8) 983-989
• 50 Koch DG, Caplan M, Reuben A. Pulmonary hypertension after liver transplantation: case presentation and review of the literature. Liver Transpl 2009; 15 (4) 407-412