Skip to main content

Advertisement

Log in

Hypoxic hepatitis: a challenging diagnosis

  • Review Article
  • Published:
Hepatology International Aims and scope Submit manuscript

Abstract

Hypoxic hepatitis (HH), one of the most common causes of acute liver injury, has a prevalence of up to 10% of admissions in intensive care units across the world. Inadequate oxygen uptake by the hepatocytes resulting in centrilobular necrosis associated with abnormally raised levels of the serum transaminases (ALT, AST) in patients with clinical history of cardiac, respiratory, or circulatory failures is the key feature of this condition. Abstracts, reviews, case reports, and research letters from various sources such as Pubmed, Proquest, Ovid, Google Scholar, and ISI Web of Knowledge dating from 1970 to 2011 were read and analyzed thoroughly. A study of 100 patients with HH, carried out from 2009 to 2010 at Tongji Hospital of Tongji University, Shanghai, People’s Republic of China, is also documented. The contributing factors leading to HH are passive congestion, ischemia, and arterial hypoxemia of the liver. Ischemia/reperfusion injury also has a major role in HH. Some of its complications are spontaneous hypoglycemia, a high level of serum ammonia, and respiratory insufficiency due to hepatopulmonary syndrome. The therapy of HH lies mainly in the treatment of the main underlying causes, and this leads to the successful reversion of HH. The aim of this review is to present a simplified concept about the etiology, pathophysiology, mechanism, clinical manifestations, diagnosis, and treatment of HH.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Bynum T, Boitnott JK, Maddrey WC. Ischemic hepatitis. Dig Dis Sci 1979;24:129–135

    Article  PubMed  CAS  Google Scholar 

  2. Fuhrmann V, Kneidinger N, Herkner H, et al. Hypoxic hepatitis: underlying conditions and risk factors for mortality in critically ill patients. Intensive Care Med 2009;35:1397–1405

    Article  PubMed  Google Scholar 

  3. Birrer R, Takuda Y, Takara T. Hypoxic hepatopathy: pathophysiology and prognosis. Intern Med 2007;46:1063–1070

    Article  PubMed  Google Scholar 

  4. Whitehead N, Hawkes ND, Hainsworth I, et al. A prospective study of the causes of notably raised aminotransferase of liver origin. Gut 1999;45:129–133

    Article  PubMed  CAS  Google Scholar 

  5. Johnson R, O’Connor C, Kerr RM. Extreme serum elevations of aspartate aminotransferase. Am J Gastroenterol 1995;90:1244–1245.

    PubMed  CAS  Google Scholar 

  6. Henrion J, Schapira M, Luwart R, et al. Hypoxic hepatitis: clinical and hemodynamic study in 142 consecutive cases. Medicine (Baltimore) 2003;82:392–406

    Article  Google Scholar 

  7. Henrion J, Descamps O, Luwaert R, et al. Hypoxic hepatitis in patients with cardiac failure: incidence in a coronary care unit and measurement of hepatic blood flow. J Hepatol 1994;21:696–703

    Article  PubMed  CAS  Google Scholar 

  8. Pauwels A, Levy VG. Ischemic hepatitis in cirrhosis: not so rare, not always lethal. J Clin Gastroenterol 1993;17:88–89

    Article  PubMed  CAS  Google Scholar 

  9. Kamiyama T, Miyakawa H, Tajiri K, Marumo F, Sato C. Ischemic hepatitis in cirrhosis: clinical features and prognostic implications. J Clin Gastroenterol 1996;22:126–130

    Article  PubMed  CAS  Google Scholar 

  10. Rashed KA, McNabb WR, Lewis RR. Ischaemic hepatitis in the elderly. Gerontology 2002;48:245–249

    Article  PubMed  Google Scholar 

  11. Fuchs S, Bogomolski-Yahalom V, Paltiel O, Ackerman Z. Ischemic hepatitis: clinical and laboratory observations of 34 patients. J Clin Gastroenterol 1998;26:183–186

    Article  PubMed  CAS  Google Scholar 

  12. Raman JS, Kochi K, Morimatsu H, Buxton B, Bellomo R. Severe ischemic early liver injury after cardiac surgery. Ann Thorac Surg 2002;74:1601–1606

    Article  PubMed  Google Scholar 

  13. Cohen JA, Kaplan MM. Left-sided heart failure presenting as hepatitis. Gastroenterology 1978;74:583–587

    PubMed  CAS  Google Scholar 

  14. Henrion J, Schapira M, Heller FR. Ischemic hepatitis: the need for precise criteria. J Clin Gastroenterol 1996;23:305

    Article  PubMed  CAS  Google Scholar 

  15. Ucgun A, Ozakyol M, Metintas H, et al. Relationship between hypoxic hepatitis and cor pulmonale in patients treated in the respiratory ICU. Int J Clin Pract 2005;59(11):1295–1300

    Article  PubMed  CAS  Google Scholar 

  16. Blich M, Shinon E, Manshano R, Edoute Y. Ischemic hepatitis induced by severe anemia. IMAJ 2003;5:208–209

    PubMed  Google Scholar 

  17. Szypowska A, et al. Acute hypoxic hepatopathy: diabetic ketoacidosis complication in an infant newly diagnosed with type 1 diabetes mellitus. Pediatr Endocrinol Diabetes Metab 2008;14:249–251

    PubMed  Google Scholar 

  18. et de Kerguennec CD, Bernuau J, et al. Acute hypoxic hepatitis (‘liver shock’): still a frequently overlooked cardiological diagnosis. Eur J Heart Fail 2004;6:561–565

    PubMed  Google Scholar 

  19. Henrion J, Minette P, Colin L, Schapira M, Delannoy A, Heller FR. Hypoxic hepatitis caused by acute exacerbation of chronic respiratory failure: a case-controlled, hemodynamic study of 17 consecutive cases. Hepatology 1999;29:427–433

    Article  PubMed  CAS  Google Scholar 

  20. Leslie BR, Head LH, Scharfenberg JC. Ischemic hepatitis from aortic dissection. Ann Intern Med 1989;110:495

    PubMed  CAS  Google Scholar 

  21. Vivarelli M, Cucchetti A, La Barba G, et al. Ischemic arterial complications after liver transplantation in the adult: multivariate analysis of risk factors. Arch Surg 2004;139:1069–1074

    Article  PubMed  Google Scholar 

  22. Shin H, Yozu R, Sumida T, Kawada S. Acute ischemic hepatic failure resulting from intraaortic balloon pump malposition. Eur J Cardiothorac Surg 2000;17:492–494

    Article  PubMed  CAS  Google Scholar 

  23. von Glinski KS, Krettek C, Blauth M, Oldhafer K-J. Hepatic ischemia as a complication after correction of post-traumatic gibbus at the thoracolumbar junction. Spine 2000;25:1040–1044

    Article  Google Scholar 

  24. Webster GJM, Kurtovic J, Lowe SA, Riordan SM. Hepatic ischemia associated with coarctation of the aorta in pregnancy: key issues in differential diagnosis. Obstet Gynecol 2004;104:1151–1154

    Article  PubMed  Google Scholar 

  25. Shibayama Y, Hashimoto K, Nakata K. Hepatic haemodynamics and microvascular architecture after portal venular embolization in the rat. J Hepatol 1992;14:94–98

    Article  PubMed  CAS  Google Scholar 

  26. Thurman RG, Ji S, Lemasters JJ. Alcohol-induced liver injury: the role of oxygen. Recent Dev Alcohol 1984;2:103–117

    Article  PubMed  CAS  Google Scholar 

  27. French SW, Benson NC, Sun PS. Centrilobular liver necrosis induced by hypoxia in chronic ethanol-fed rats. Hepatology 1984;4:912–917

    Article  PubMed  CAS  Google Scholar 

  28. Dahn MS, Wilson RF, Lange P, Stone A, Jacobs LA. Hepatic parenchymal oxygen tension following injury and sepsis. Arch Surg 1990;125:441–443

    Article  PubMed  CAS  Google Scholar 

  29. Wiedersberg H, Pawlowski P. Anemic necrosis of the liver after umbilical vein catheterization. Helv Paediatr Acta 1979;34:53–62

    PubMed  CAS  Google Scholar 

  30. Menon KVN, Shah V, Kamath PS. The Budd–Chiari syndrome. N Engl J Med 2004;350:578–85

    Article  PubMed  CAS  Google Scholar 

  31. Han D-W. Intestinal endotoxemia as a pathogenetic mechanism in liver failure. World J Gastroenterol 2002;8:961–965

    PubMed  Google Scholar 

  32. Asaka S, Shibayama Y, Nakata K. Pathogenesis of focal and random hepatocellular necrosis in endotoxemia: microscopic observation in vivo. Liver 1996;16:183–187

    PubMed  CAS  Google Scholar 

  33. Ring A, Stremmel W. The hepatic microvascular responses to sepsis. Semin Thromb Hemost 2000;26:589–594

    Article  PubMed  CAS  Google Scholar 

  34. Shibayama Y, Urano T, Asaka S, Hashimoto K, Nakata K. Pathogenesis of centrilobular necrosis following congestion of the liver. J Gastroenterol Hepatol 1993;8:530–534

    Article  PubMed  CAS  Google Scholar 

  35. Shibayama Y. The role of hepatic venous congestion and endotoxaemia in the production of fulminant hepatic failure secondary to congestive heart failure. J Pathol 1987;151:133–138

    Article  PubMed  CAS  Google Scholar 

  36. Henrion J, Colin L, Schapira M, Heller FR. Hypoxic hepatitis caused by severe hypoxemia from obstructive sleep apnea. J Clin Gastroenterol 1997;24:245–249

    Article  PubMed  CAS  Google Scholar 

  37. Mathurin P, Durand F, Ganne N, et al. Ischemic hepatitis due to obstructive sleep apnea. Gastroenterology 1995;109:1682–1684

    Article  PubMed  CAS  Google Scholar 

  38. Omata M, Johnson CS, Tong M, Tatter D. Pathological spectrum of liver diseases in sickle cell disease. Dig Dis Sci 1986;31:247–256

    Article  PubMed  CAS  Google Scholar 

  39. Charlotte F, Bachir D, Nenert M, et al. Vascular lesions of the liver in sickle cell disease: a clinicopathological study in 26 living patients. Arch Pathol Lab Med 1995;119:46–52

    PubMed  CAS  Google Scholar 

  40. Teixeira AL, Viana MB, Roquete ML, Toppa NH. Sickle cell disease: a clinical and histopathologic study of the liver in living children. J Pediatr Hematol Oncol 2002;24:125–129

    Article  PubMed  Google Scholar 

  41. Mills LR, Mwakyusa D, Milner PF. Histopathologic features of liver biopsy specimens in sickle cell disease. Arch Pathol Lab Med 1988;112:290–294

    PubMed  CAS  Google Scholar 

  42. Bauer TW, Moore GW, Hutchins GM. The liver in sickle cell disease: a clinicopathologic study of 70 patients. Am J Med 1980;69:833–837

    Article  PubMed  CAS  Google Scholar 

  43. Banerjee S, Owen C, Chopra S. Sickle cell hepatopathy. Hepatology 2001;33:1021–1028

    Article  PubMed  CAS  Google Scholar 

  44. Sheehy TW. Sickle cell hepatopathy. South Med J 1977;70:533–538

    Article  PubMed  CAS  Google Scholar 

  45. Saltzman JR, Johnston DE. Sickle cell crisis and cocaine hepatotoxicity. Am J Gastroenterol 1992;87:1661–1664

    PubMed  CAS  Google Scholar 

  46. Friedman LS. Mechanisms of disease: mechanisms of hepatic fibrosis and therapeutic implications. Gastroenterol Hepatol 2004;1:98–105

    Google Scholar 

  47. Cesur S, et al. Acute hepatic failure in a case of acute lymphoblastic leukemia. Tur J Med Sci 2004;34:275–279

    Google Scholar 

  48. Verschuur A. Acute myelomonocytic leukemia. Orphanet Encyclopedia. May 2004

  49. Kumar V, Abbas AK, Fausto N. Cellular adaptations, cell injury, and cell death. In Kumar V, Abbas AK, Fausto N, editors. Robbins and Cotrans Pathologic Basis of Disease. 7th ed. PA: Elsevier; 2005. 3–46.

    Google Scholar 

  50. Massip-Salcedo M, Roselló-Catafau J, Prieto J, et al. The response of the hepatocyte to ischemia. Liver Int 2007;27:6–16

    Article  PubMed  CAS  Google Scholar 

  51. Jaeschke H. Reactive oxygen and ischemia/reperfusion injury of the liver. Chem Biol Interact 1991;79:115

    Article  PubMed  CAS  Google Scholar 

  52. Cursio R, Guggenheim J, Ricci J, et al. A caspase inhibitor fully protects rats against lethal normothermic liver ischaemia by inhibition of liver apoptosis. FASEB J 1999;13:253–261

    PubMed  CAS  Google Scholar 

  53. Yadav SS, Howell DN, Steeber DA, et al. P-Selectin mediates reperfusion injury through neutrophil and platelet sequestration in the warm ischemic mouse liver. Hepatology 1999;29:1494

    Article  PubMed  CAS  Google Scholar 

  54. Lentsch AB, Kato A, Yoshidome H. Inflammatory mechanisms and therapeutic strategies for warm hepatic ischemia/reperfusion injury. Hepatology 2000;32(2):169–173

    Article  PubMed  CAS  Google Scholar 

  55. Kohli V, Madden JF, Bentley RC, Clavien PA. Calpain mediates ischemic injury of the liver through modulation of apoptosis and necrosis. Gastroenterology 1999;116:168–178

    Article  PubMed  CAS  Google Scholar 

  56. Camargo CA Jr, Madden JF, Gao W. Interleukin-6 protects liver against warm ischemia/reperfusion injury and promotes hepatocyte proliferation in the rodent. Hepatology 1997;26:1513

    Article  PubMed  CAS  Google Scholar 

  57. Wang Y, Mathews WR, Guido DM, et al. Inhibition of nitric oxide synthesis aggravates reperfusion injury after hepatic ischemia and endotoxemia. Shock 1995;4(4):282–8

    Article  PubMed  CAS  Google Scholar 

  58. Fuhrmann V, Jäger B, Zubkova A, et al. Hypoxic hepatitis: epidemiology, pathophysiology and clinical management. Wien Klin Wochenschr 2010;122:129–139

    Article  PubMed  Google Scholar 

  59. Stravitz R, Kramer A, Davern T, et al. Intensive care of patients with acute liver failure: recommendations of the U.S. Acute Liver Failure Study Group. Crit Care Med 2007;35:2498–2508

    Article  PubMed  Google Scholar 

  60. De Jonghe B, Cheval C, Misset B, et al. Relationship between blood lactate and early hepatic dysfunction in acute circulatory failure. J Crit Care 1999;14:7–11

    Article  PubMed  Google Scholar 

  61. Kahn JA, Haker KM, Petrovic LM, Arnaout WS, Koobatian G, Fong TL. Radiographic findings of ischemic hepatitis in a cirrhotic patient. J Comput Assist Tomogr 2000;24:887–889

    Article  PubMed  CAS  Google Scholar 

  62. Motoyama S, Minamiya Y, Saito S, et al. Hydrogen peroxide derived from hepatocytes induces sinusoidal endothelial cell apoptosis in perfused hypoxic rat liver. Gastroenterology. 1998;114:153–163

    Article  PubMed  CAS  Google Scholar 

  63. Schenk P, Schoniger-Hekele M, Fuhrmann V, et al. Prognostic significance of the hepatopulmonary syndrome in patients with cirrhosis. Gastroenterology 2003;125:1042–1052

    Article  PubMed  Google Scholar 

  64. Fuhrmann V, Madl C, Mueller C, et al. Hepatopulmonary syndrome in patients with hypoxic hepatitis. Gastroenterology 2006;131:67–69

    Article  Google Scholar 

  65. Gitlin N, Serio K. Ischemic hepatitis: widening horizons. Am J Gastroenterol 1992;87:831–836

    PubMed  CAS  Google Scholar 

  66. Fuhrmann V, Drolz A, Kneidinger N, et al. Hyperammonemia in patients with hypoxic hepatitis. Gut 2009;58(Suppl2):P0450

    Google Scholar 

  67. Mitzner S, Stange J, Klammt S, et al. Extracorporeal detoxification using the molecular adsorbent recirculating system for critically ill patients with liver failure. J Am Soc Nephrol 2001;12:S75–S82

    PubMed  CAS  Google Scholar 

  68. Stefoni S, Coli L, Bolondi L, et al. Molecular adsorbent recirculating system (MARS) application in liver failure: clinical and hemodepurative results in 22 patients. Int J Artif Organs 2006;29:207–218

    PubMed  CAS  Google Scholar 

  69. Laleman W, Wilmer A, Evenepoel P, et al. Effect of the molecular adsorbent recirculating system and Prometheus devices in systemic haemodynamics and vasoactive agents in patients with acute-on-chronic liver failure. Crit Care 2006;10:R108

    Article  PubMed  Google Scholar 

  70. Schmidt L, Wang LP, Hansen BA, et al. Systemic hemodynamic effects of treatment with the molecular adsorbent recirculating system in patients with hyperacute liver failure: a prospective controlled trial. Liver Transpl 2003;9:290–297

    Article  PubMed  Google Scholar 

  71. Sen S, Loock J, Peszynski P, et al. Albumin dialysis reduces portal pressure acutely in patients with severe alcoholic hepatitis. J Hepatol 2005;43:142–148

    Article  PubMed  CAS  Google Scholar 

  72. Hetz H, Faybik P, Berlakovich G, et al. Molecular adsorbent recirculating system in patients with early allograft dysfunction after liver transplantation. Liver Transpl 2006;12:1357–1364

    Article  PubMed  Google Scholar 

  73. Kume M, Yamamoto Y, Yamagami K, et al. Pharmacological hepatic preconditioning: involvement of 70-kDa heat shock proteins (HSP72 and HSP73) in ischaemic tolerance after intravenous administration of doxorubicin. Br J Surg 2000;87:1168–1175

    Article  PubMed  CAS  Google Scholar 

  74. Gedik E, Girgin S, Ozturk H, Obay BD, Ozturk H, Buyukbayram H. Resveratrol attenuates oxidative stress and histological alterations induced by liver ischemia/reperfusion in rats. World J Gastroenterol 2008;14(46):7101–7106

    Article  PubMed  CAS  Google Scholar 

  75. Duchen MR. Mitochondria and calcium: from cell signalling to cell death. J Physiol 2000;529(Pt 1):57–68

    Article  PubMed  CAS  Google Scholar 

  76. Gerbes AL, Vollmar AM, Kiemer AK, Bilzer M. The guanylate cyclase-coupled natriuretic peptide receptor: a new target for prevention of cold ischemia-reperfusion damage of the rat liver. Hepatology 1998;28:1309–1317

    Article  PubMed  CAS  Google Scholar 

  77. Raddatz A, Kubulus D, Winning J, et al. Dobutamine improves liver function after hemorrhagic shock through induction of heme oxygenase-1. Am J Respir Crit Care Med 2006;174(2):198–207

    Article  PubMed  CAS  Google Scholar 

  78. Bilbao G, Contreras JL, et al. Reduction of ischemia-reperfusion injury of the liver by in vivo adenovirus-mediated gene transfer of the antiapoptotic bcl-2 gene. Ann Surg 1999;230(2):185

    Article  PubMed  CAS  Google Scholar 

  79. Jiang N, Zhang X, Zheng X, et al. Targeted gene silencing of TLR4 using liposomal nanoparticles for preventing liver ischemia reperfusion injury. Am J Transplant 2011;11(9):1835–1844

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Goolab Trilok.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Trilok, G., Qing, Y.C. & Li-Jun, X. Hypoxic hepatitis: a challenging diagnosis. Hepatol Int 6, 663–669 (2012). https://doi.org/10.1007/s12072-011-9336-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12072-011-9336-1

Keywords

Navigation