The Journal of Pediatrics
Volume 147, Issue 1 , Pages 3-4, July 2005

Many Faces of Portopulmonary Hypertension

  • Michael J. Krowka, MD

      Affiliations

    • Corresponding Author InformationReprint requests: Michael J. Krowka, MD, 200 1st Street SW, Rochester, MN 55905.

Professor of Medicine, Division of Pulmonary and Critical Care, Mayo Clinic, Rochester, MN

See related article, p 20.

Article Outline

DE, Doppler echocardiography, OLT, Orthotopic liver transplantation, POPH, Portopulmonary hypertension, RV, Right ventricle

 

Years of portal hypertension, dyspnea with exertion, a new murmur, syncopal episodes, and sudden death. These elements comprise only part of our experiences in caring for patients with the entity characterized as portopulmonary hypertension (POPH)—the evolution of pulmonary artery hypertension as a consequence of portal hypertension pathophysiology.1 Sadly, we are reminded in this issue of The Journal of Pediatrics by Condino et al2 that POPH is not an exclusive syndrome affecting only adults with liver disease and portal hypertension. These authors succinctly summarize the varied clinical courses of 7 pediatric patients with severe POPH (mean pulmonary artery pressure >50 mm Hg). Indeed, POPH is an uncommon syndrome (4% to 14.5% frequency at major liver transplantation centers), at times confusing even the best clinicians who have to deal with overlapping signs and symptoms of advanced liver disease and progressive pulmonary artery hypertension. The specific liver-lung mediators of this syndrome are not clearly identified.1 My comments focus on screening, treatment, and orthotopic liver transplantation (OLT).

Back to Article Outline

Screening 

From adult experience in the era of pre-OLT evaluation, we have learned that the diagnosis of POPH was frequently missed. In a retrospective review of 43 patients with POPH from 18 peer-reviewed studies, 65% of cases were first diagnosed in the operating room during the liver transplantation. Intraoperative death directly caused by cardiopulmonary events followed in 2 patients.3 Condino et al2 correctly point out that chest radiography and electrocardiography are insensitive screening tools if we are hoping to recognize this syndrome (or any cause of pulmonary artery hypertension for that matter) in its earliest stages. Screening transthoracic Doppler echocardiography (DE) in the setting of advanced liver disease is noninvasive, quantitative (estimate of right ventricle (RV) systolic pressure), and qualitative (assesses RV size and function). Importantly, DE provides a guide as to who should undergo right-sided heart catheterization to confirm the diagnosis of POPH.4 Currently at my institution, RV systolic pressure >50 mm Hg suggests POPH until proven otherwise and right-sided heart catheterization is advised. No doubt, most patients with portal hypertension, and up to 25% with RV systolic pressures >50 mm Hg, simply have a hyperdynamic, high flow state, documented by high cardiac output and low calculated pulmonary vascular resistance. As expected from the spectrum of disease noted in POPH (endothelial and smooth muscle proliferation, in situ thrombosis, and plexogenic lesions), an increase in pulmonary arterial resistance to flow from the right ventricle is a key hemodynamic feature of POPH.1 Right-side heart failure is the end result of unrelenting obstruction to pulmonary arterial flow.

Back to Article Outline

Treatment 

Continuous intravenous epoprostenol has been the “drug of choice” for patients with POPH considered for OLT at my institution on the basis of empiric experience.5 Acute and long-term improvement in pulmonary hemodynamics has been related to vasodilation, antiplatelet aggregating effect, inotropic effect, and presumed vascular remodeling. Published POPH treatment experiences are limited for the most part to case reports. The evolving use of intravenous prostanoids,5, 6, 7 inhaled iloprost,8, 9 endothelin receptor antagonists,10, 11, 12, 13, 14 and phosphodiesterase inhibitors15 in highly selected patients with POPH provides encouraging options. However, no randomized or open-label multicenter trials have been conducted specifically for POPH to date.

Back to Article Outline

OLT 

Intraoperative and postoperative mortality rates remain high in the setting of adult POPH, in spite of efforts to screen and deny OLT to some patients with POPH with the most severe hemodynamic situations.16 Pre-OLT use of prostanoids (or any other agent) has not been studied systematically in any age group. Which pre-OLT pulmonary vasomodulating agent to select, duration of treatment, and hemodynamic therapy goals that would favor successful OLT are topics that are evolving. Whether POPH is “cured” or simply improved with a combination of OLT and vasomodulating agents remains a question to be answered. Finally, we must be aware that pulmonary artery hypertension can occur clinically after successful OLT.17

Should we seek living-donor OLT or a higher priority for OLT if less than severe POPH exists (ie, higher pediatric end-stage liver disease score)? The answer should depend on Institutional Review Board–approved investigation that demonstrates OLT in selected subgroups of POPH can result in normalized/improved pulmonary hemodynamics and favorable long-term survival. It is time to make future POPH management decisions from more than our anecdotal case reports.

We had hoped to see very few young faces with POPH. That may not happen. So, as we have done for adults when OLT is considered, we should strive to identify an earlier face of POPH. The report of Condino et al2 clearly paints the picture of dismal outcome, despite best efforts, following the diagnosis of severe POPH. Institutional Review Board–approved studies to address screening Doppler transthoracic echocardiography, hemodynamic subgroups via right-side heart catheterization, “earlier” treatment (including a higher PELD score or living-donor OLT in selected patients?) and research-oriented patient registries make sense. Maybe then we can improve quality of life and survival rates for all age groups after the diagnosis of POPH.

Back to Article Outline

References 

  1. Blendis L, Wong F. Portopulmonary hypertension: an increasingly important complication of cirrhosis. Gastroenterology. 2003;126:622–624
  2. Condino AA, O'Connor JA, Narkawicz MR, Mengshol S, Whitworth JR, Claussen L, et al. Portopulmonary hypertension in pediatric patients. J Pedriatr. 2005;147:20–26
  3. Krowka MJ, Plevak DJ, Findlay JF, Rosen CB, Wiesner RH, Krom RAF. Pulmonary hemodynamics and perioperative cardiopulmonary related mortality in patients with portopulmonary hypertension undergoing liver transplantation. Liver Transpl. 2000;6:443–450
  4. Kim WR, Krowka MJ, Plevak DJ, Lee J, Rettke SR, Frantz RF, et al. Accuracy of Doppler echocardiography in the assessment of portopulmonary hypertension in liver transplant candidates. Liver Transpl. 2000;6:453–458
  5. Krowka MJ, Frantz RF, McGoon MD, Wiesner RH. Improvement if pulmonary hemodynamics during intravenous epoprostenol (prostacyclin): a study of 15 patients with moderate to severe portopulmonary hypertension. Hepatology. 1999;30:641–648
  6. Minder S, Fischier M, Muelhaupt B, Zalunardo MO, Jenni R, Clavien PA, et al. Intravenous iloprost bridging to orthotopic liver transplantation in portopulmonary hypertension. Eur Respir J. 2004;24:703–707
  7. Sulica E, Emre S, Poon M. Medical management of portopulmonary hypertension and right heart failure prior to living-related liver transplantation. CHF. 2004;10:192–194
  8. Halank M, Marx C, Miehlke S, Hoeftken G. Use of inhaled iloprost in the treatment of portopulmonary hypertension. J of Gastroenterology. 2004;39:1222–1223
  9. Molnar C, Alber H, Cooleselli D, Vogel W, Kahler CM. Successful switch from inhalitive iloprost to oral bosentan in portopulmonary hypertension associated with liver cirrhosis. Wien Klinis Woch. 2004;116:627–630
  10. Halank M, Miehlke S, Hoeffken G, Schmeisser A, Schulze M, Strasser RH. Use of oral endothelin-receptor antagonist bosentan in the treatment of portopulmonary hypertension. Transplantation. 2004;77:1775–1776
  11. Hinterhuber L, Graziaedi IW, Kahler CM, Jaschke W, Vogel W. Endothelin-receptor antagonist treatment of portopulmonary hypertension. Clin Gastroenterol Hepatol. 2004;2:1039–1042
  12. Kuntzen C, Gulberg V, Gerbes AL. Use of a mixed endothelin receptor antagonist in portopulmonary hypertension: a safe and effective therapy?. Gastroenterology. 2005;128:64–68
  13. Hoeper MM, Halank M, Hoeffken G, Seyfarth HJ, Schauer J, Niedermer J, et al. Bosentan for the treatment of portopulmonary hypertension. Eur Respir J. 2005;25:502–508
  14. Clift PF, Bramhall S, Isaac JL. Successful treatment of severe portopulmonary hypertension after liver transplantation by bosentan. Transplantation. 2004;77:1774–1776
  15. Makisalo H, Koivusalo A, Vakkuri A, Hockerstedt K. Sildenafil for portopulmonary hypertension in a patient undergoing liver transplantation. Liver Transpl. 2004;10:945–950
  16. Krowka MJ, Mandell SM, Ramsay MAE, Kawut SM, Fallon MB, Manzarbeitia C, et al. Hepatopulmonary syndrome and portopulmonary hypertension: a report of the multicenter liver transplant database. Liver Transpl. 2004;10:174–182
  17. Shah T, Isaac J, Adams D, Kelly D, the Liver Units . Development of hepatopulmonary syndrome and portopulmonary hypertension in a paediatric liver transplant patient. Pediatr Transpl. 2005;9:127–131

PII: S0022-3476(05)00321-5

doi:10.1016/j.jpeds.2005.04.014

The Journal of Pediatrics
Volume 147, Issue 1 , Pages 3-4, July 2005

Article Tools