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Hepatopulmonary syndrome in adults: Prevalence, causes, clinical manifestations, and diagnosis

Authors
Paul A Lange, MD
James K Stoller, MD, MS
Section Editor
Jess Mandel, MD
Deputy Editor
Geraldine Finlay, MD

INTRODUCTION

Hepatopulmonary syndrome (HPS) is characterized by the triad of abnormal arterial oxygenation caused by intrapulmonary vascular dilatations (IPVDs) in the setting of liver disease, portal hypertension, or congenital portosystemic shunts [1].

The prevalence, causes, clinical manifestations, and diagnostic evaluation of HPS are reviewed here. The natural history, treatment, and outcomes of HPS are discussed separately. (See "Hepatopulmonary syndrome in adults: Natural history, treatment, and outcomes".)

PREVALENCE

Estimates of the prevalence of HPS among patients with chronic liver disease range from 4 to 47 percent (on average one quarter), depending upon the diagnostic criteria, methods used, and population studied [2-13]. As examples:

In one prospective study of 111 patients with cirrhosis, HPS was reported in 24 percent when transthoracic contrast echocardiography, blood gas analysis, and pulmonary function testing were used for its detection [2].

In another prospective study of patients with liver cirrhosis, 26 percent had HPS by similar criteria [7].

                               

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Literature review current through: Nov 2016. | This topic last updated: Mon Sep 19 00:00:00 GMT+00:00 2016.
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References
Top
  1. Krowka MJ, Fallon MB, Kawut SM, et al. International Liver Transplant Society Practice Guidelines: Diagnosis and Management of Hepatopulmonary Syndrome and Portopulmonary Hypertension. Transplantation 2016; 100:1440.
  2. Schenk P, Schöniger-Hekele M, Fuhrmann V, et al. Prognostic significance of the hepatopulmonary syndrome in patients with cirrhosis. Gastroenterology 2003; 125:1042.
  3. Krowka MJ, Tajik AJ, Dickson ER, et al. Intrapulmonary vascular dilatations (IPVD) in liver transplant candidates. Screening by two-dimensional contrast-enhanced echocardiography. Chest 1990; 97:1165.
  4. Stoller JK, Lange PA, Westveer MK, et al. Prevalence and reversibility of the hepatopulmonary syndrome after liver transplantation. The Cleveland Clinic experience. West J Med 1995; 163:133.
  5. Hopkins WE, Waggoner AD, Barzilai B. Frequency and significance of intrapulmonary right-to-left shunting in end-stage hepatic disease. Am J Cardiol 1992; 70:516.
  6. Arguedas MR, Singh H, Faulk DK, Fallon MB. Utility of pulse oximetry screening for hepatopulmonary syndrome. Clin Gastroenterol Hepatol 2007; 5:749.
  7. Younis I, Sarwar S, Butt Z, et al. Clinical characteristics, predictors, and survival among patients with hepatopulmonary syndrome. Ann Hepatol 2015; 14:354.
  8. Ferreira PP, Camara EJ, Paula RL, et al. Prevalence of hepatopulmonary syndrome in patients with decompensated chronic liver disease and its impact on short-term survival. Arq Gastroenterol 2008; 45:34.
  9. Schenk P, Fuhrmann V, Madl C, et al. Hepatopulmonary syndrome: prevalence and predictive value of various cut offs for arterial oxygenation and their clinical consequences. Gut 2002; 51:853.
  10. De BK, Sen S, Biswas PK, et al. Hepatopulmonary syndrome in inferior vena cava obstruction responding to cavoplasty. Gastroenterology 2000; 118:192.
  11. Gupta D, Vijaya DR, Gupta R, et al. Prevalence of hepatopulmonary syndrome in cirrhosis and extrahepatic portal venous obstruction. Am J Gastroenterol 2001; 96:3395.
  12. Abrams GA, Jaffe CC, Hoffer PB, et al. Diagnostic utility of contrast echocardiography and lung perfusion scan in patients with hepatopulmonary syndrome. Gastroenterology 1995; 109:1283.
  13. Kim BJ, Lee SC, Park SW, et al. Characteristics and prevalence of intrapulmonary shunt detected by contrast echocardiography with harmonic imaging in liver transplant candidates. Am J Cardiol 2004; 94:525.
  14. Vachiéry F, Moreau R, Hadengue A, et al. Hypoxemia in patients with cirrhosis: relationship with liver failure and hemodynamic alterations. J Hepatol 1997; 27:492.
  15. Krowka MJ, Dickson ER, Cortese DA. Hepatopulmonary syndrome. Clinical observations and lack of therapeutic response to somatostatin analogue. Chest 1993; 104:515.
  16. Krowka MJ, Wiseman GA, Burnett OL, et al. Hepatopulmonary syndrome: a prospective study of relationships between severity of liver disease, PaO(2) response to 100% oxygen, and brain uptake after (99m)Tc MAA lung scanning. Chest 2000; 118:615.
  17. Rodríguez-Roisin R, Krowka MJ. Hepatopulmonary syndrome--a liver-induced lung vascular disorder. N Engl J Med 2008; 358:2378.
  18. Kaymakoglu S, Kahraman T, Kudat H, et al. Hepatopulmonary syndrome in noncirrhotic portal hypertensive patients. Dig Dis Sci 2003; 48:556.
  19. Gorgy AI, Jonassaint NL, Stanley SE, et al. Hepatopulmonary syndrome is a frequent cause of dyspnea in the short telomere disorders. Chest 2015; 148:1019.
  20. Fuhrmann V, Madl C, Mueller C, et al. Hepatopulmonary syndrome in patients with hypoxic hepatitis. Gastroenterology 2006; 131:69.
  21. Trilok G, Qing YC, Li-Jun X. Hypoxic hepatitis: a challenging diagnosis. Hepatol Int 2012; 6:663.
  22. El-Shabrawi MH, Omran S, Wageeh S, et al. (99m)Technetium-macroaggregated albumin perfusion lung scan versus contrast enhanced echocardiography in the diagnosis of the hepatopulmonary syndrome in children with chronic liver disease. Eur J Gastroenterol Hepatol 2010; 22:1006.
  23. Regev A, Yeshurun M, Rodriguez M, et al. Transient hepatopulmonary syndrome in a patient with acute hepatitis A. J Viral Hepat 2001; 8:83.
  24. Fussner LA, Iyer VN, Cartin-Ceba R, et al. Intrapulmonary vascular dilatations are common in portopulmonary hypertension and may be associated with decreased survival. Liver Transpl 2015; 21:1355.
  25. Nunes H, Lebrec D, Mazmanian M, et al. Role of nitric oxide in hepatopulmonary syndrome in cirrhotic rats. Am J Respir Crit Care Med 2001; 164:879.
  26. Carter EP, Hartsfield CL, Miyazono M, et al. Regulation of heme oxygenase-1 by nitric oxide during hepatopulmonary syndrome. Am J Physiol Lung Cell Mol Physiol 2002; 283:L346.
  27. Zhang HY, Han DW, Wang XG, et al. Experimental study on the role of endotoxin in the development of hepatopulmonary syndrome. World J Gastroenterol 2005; 11:567.
  28. Zhang HY, Han DW, Zhao ZF, et al. Multiple pathogenic factor-induced complications of cirrhosis in rats: a new model of hepatopulmonary syndrome with intestinal endotoxemia. World J Gastroenterol 2007; 13:3500.
  29. Grace JA, Angus PW. Hepatopulmonary syndrome: update on recent advances in pathophysiology, investigation, and treatment. J Gastroenterol Hepatol 2013; 28:213.
  30. Koch DG, Bogatkevich G, Ramshesh V, et al. Elevated levels of endothelin-1 in hepatic venous blood are associated with intrapulmonary vasodilatation in humans. Dig Dis Sci 2012; 57:516.
  31. Rolla G, Brussino L, Colagrande P, et al. Exhaled nitric oxide and impaired oxygenation in cirrhotic patients before and after liver transplantation. Ann Intern Med 1998; 129:375.
  32. Schroeder RA, Ewing CA, Sitzmann JV, Kuo PC. Pulmonary expression of iNOS and HO-1 protein is upregulated in a rat model of prehepatic portal hypertension. Dig Dis Sci 2000; 45:2405.
  33. Fallon MB, Abrams GA, Luo B, et al. The role of endothelial nitric oxide synthase in the pathogenesis of a rat model of hepatopulmonary syndrome. Gastroenterology 1997; 113:606.
  34. Tang L, Luo B, Patel RP, et al. Modulation of pulmonary endothelial endothelin B receptor expression and signaling: implications for experimental hepatopulmonary syndrome. Am J Physiol Lung Cell Mol Physiol 2007; 292:L1467.
  35. Thenappan T, Goel A, Marsboom G, et al. A central role for CD68(+) macrophages in hepatopulmonary syndrome. Reversal by macrophage depletion. Am J Respir Crit Care Med 2011; 183:1080.
  36. Cremona G, Higenbottam TW, Mayoral V, et al. Elevated exhaled nitric oxide in patients with hepatopulmonary syndrome. Eur Respir J 1995; 8:1883.
  37. Rolla G, Brussino L, Colagrande P, et al. Exhaled nitric oxide and oxygenation abnormalities in hepatic cirrhosis. Hepatology 1997; 26:842.
  38. Carter EP, Sato K, Morio Y, McMurtry IF. Inhibition of K(Ca) channels restores blunted hypoxic pulmonary vasoconstriction in rats with cirrhosis. Am J Physiol Lung Cell Mol Physiol 2000; 279:L903.
  39. Schenk P, Madl C, Rezaie-Majd S, et al. Methylene blue improves the hepatopulmonary syndrome. Ann Intern Med 2000; 133:701.
  40. Tumgor G, Berdeli A, Arikan C, et al. Mcp-1, eNOS, tPA and PAI-1 gene polymorphism and correlation of genotypes and phenotypes in hepatopulmonary syndrome. Dig Dis Sci 2008; 53:1345.
  41. Roberts KE, Kawut SM, Krowka MJ, et al. Genetic risk factors for hepatopulmonary syndrome in patients with advanced liver disease. Gastroenterology 2010; 139:130.
  42. Tumgor G. Cirrhosis and hepatopulmonary syndrome. World J Gastroenterol 2014; 20:2586.
  43. Andrivet P, Cadranel J, Housset B, et al. Mechanisms of impaired arterial oxygenation in patients with liver cirrhosis and severe respiratory insufficiency. Effects of indomethacin. Chest 1993; 103:500.
  44. Agusti AG, Roca J, Rodriguez-Roisin R, et al. Pulmonary hemodynamics and gas exchange during exercise in liver cirrhosis. Am Rev Respir Dis 1989; 139:485.
  45. Rodríguez-Roisin R, Agustí AG, Roca J. The hepatopulmonary syndrome: new name, old complexities. Thorax 1992; 47:897.
  46. Hedenstierna G, Söderman C, Eriksson LS, Wahren J. Ventilation-perfusion inequality in patients with non-alcoholic liver cirrhosis. Eur Respir J 1991; 4:711.
  47. Genovesi MG, Tierney DF, Taplin GV, Eisenberg H. An intravenous radionuclide method to evaluate hypoxemia caused by abnormal alveolar vessels. Limitation of conventional techniques. Am Rev Respir Dis 1976; 114:59.
  48. Davis HH 2nd, Schwartz DJ, Lefrak SS, et al. Alveolar-capillary oxygen disequilibrium in hepatic cirrhosis. Chest 1978; 73:507.
  49. Fritz JS, Fallon MB, Kawut SM. Pulmonary vascular complications of liver disease. Am J Respir Crit Care Med 2013; 187:133.
  50. Rodriguez-Roisin R, Roca J, Agusti AG, et al. Gas exchange and pulmonary vascular reactivity in patients with liver cirrhosis. Am Rev Respir Dis 1987; 135:1085.
  51. Cheng TO. Mechanisms of platypnea-orthodeoxia: what causes water to flow uphill? Circulation 2002; 105:e47.
  52. Gómez FP, Martínez-Pallí G, Barberà JA, et al. Gas exchange mechanism of orthodeoxia in hepatopulmonary syndrome. Hepatology 2004; 40:660.
  53. Krowka MJ, Cortese DA. Hepatopulmonary syndrome: an evolving perspective in the era of liver transplantation. Hepatology 1990; 11:138.
  54. Köksal D, Kaçar S, Köksal AS, et al. Evaluation of intrapulmonary vascular dilatations with high-resolution computed thorax tomography in patients with hepatopulmonary syndrome. J Clin Gastroenterol 2006; 40:77.
  55. Chen YA, Prabhudesai V, Castel H, Gupta S. CT Scan Does Not Differentiate Patients with Hepatopulmonary Syndrome from Other Patients with Liver Disease. PLoS One 2016; 11:e0158637.
  56. Suga K, Kawakami Y, Iwanaga H, et al. Findings of hepatopulmonary syndrome on breath-hold perfusion SPECT-CT fusion images. Ann Nucl Med 2009; 23:413.
  57. Lima BL, França AV, Pazin-Filho A, et al. Frequency, clinical characteristics, and respiratory parameters of hepatopulmonary syndrome. Mayo Clin Proc 2004; 79:42.
  58. Gupta S, Nayyar D, Pomier-Layrargues G. Variability of oxygenation in possible hepatopulmonary syndrome: effects of requiring two abnormal arterial blood gas results for diagnosis. Dig Dis Sci 2015; 60:1848.
  59. Kochar R, Tanikella R, Fallon MB. Serial pulse oximetry in hepatopulmonary syndrome. Dig Dis Sci 2011; 56:1862.
  60. Abrams GA, Sanders MK, Fallon MB. Utility of pulse oximetry in the detection of arterial hypoxemia in liver transplant candidates. Liver Transpl 2002; 8:391.
  61. Rodríguez-Roisin R, Krowka MJ, Hervé P, et al. Pulmonary-Hepatic vascular Disorders (PHD). Eur Respir J 2004; 24:861.
  62. Naeije, R, Melot, C, Hallemans, R, et al. Pulmonary hemodynamics in liver cirrhosis. Semin Respir Med 1985; 7:164.
  63. Lange PA, Stoller JK. The hepatopulmonary syndrome. Ann Intern Med 1995; 122:521.
  64. Lenci I, Alvior A, Manzia TM, et al. Saline contrast echocardiography in patients with hepatopulmonary syndrome awaiting liver transplantation. J Am Soc Echocardiogr 2009; 22:89.
  65. Pouriki S, Alexopoulou A, Chrysochoou C, et al. Left ventricle enlargement and increased systolic velocity in the mitral valve are indirect markers of the hepatopulmonary syndrome. Liver Int 2011; 31:1388.
  66. Krowka MJ, Mandell MS, Ramsay MA, et al. Hepatopulmonary syndrome and portopulmonary hypertension: a report of the multicenter liver transplant database. Liver Transpl 2004; 10:174.
  67. Khabbaza JE, Krasuski RA, Tonelli AR. Intrapulmonary shunt confirmed by intracardiac echocardiography in the diagnosis of hepatopulmonary syndrome. Hepatology 2013; 58:1514.
  68. Nemec JJ, Davison MB, Marwick TH, et al. Detection and evaluation of intrapulmonary vascular shunt with "contrast Doppler" transesophageal echocardiography. J Am Soc Echocardiogr 1991; 4:79.
  69. Aller R, Moya JL, Moreira V, et al. Diagnosis of hepatopulmonary syndrome with contrast transesophageal echocardiography: advantages over contrast transthoracic echocardiography. Dig Dis Sci 1999; 44:1243.
  70. Wolfe JD, Tashkin DP, Holly FE, et al. Hypoxemia of cirrhosis: detection of abnormal small pulmonary vascular channels by a quantitative radionuclide method. Am J Med 1977; 63:746.
  71. Krowka MJ. Management of pulmonary complications in pretransplant patients. Clin Liver Dis 2011; 15:765.
  72. Seward JB, Hayes DL, Smith HC, et al. Platypnea-orthodeoxia: clinical profile, diagnostic workup, management, and report of seven cases. Mayo Clin Proc 1984; 59:221.
  73. Kinasewitz GT, Keddissi JI. Hepatic hydrothorax. Curr Opin Pulm Med 2003; 9:261.
  74. Krowka MJ, Cortese DA. Pulmonary aspects of liver disease and liver transplantation. Clin Chest Med 1989; 10:593.
  75. Ioachimescu OC, Mehta AC, Stoller JK. Hepatopulmonary syndrome following portopulmonary hypertension. Eur Respir J 2007; 29:1277.
  76. Justino H, Sanders K, McLin VA. Rapid progression from hepatopulmonary syndrome to portopulmonary hypertension in an adolescent female with hypopituitarism. J Pediatr Gastroenterol Nutr 2010; 50:334.
  77. Pham DM, Subramanian R, Parekh S. Coexisting hepatopulmonary syndrome and portopulmonary hypertension: implications for liver transplantation. J Clin Gastroenterol 2010; 44:e136.