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Hypoxic hepatitis: underlying conditions and risk factors for mortality in critically ill patients

Abstract

Purpose

Hypoxic hepatitis (HH) is a frequent cause of acute hepatocellular damage at the intensive care unit. Although mortality is reported to be high, risk factors for mortality in this population are unknown.

Methods

One-hundred and seventeen consecutive patients with HH were studied prospectively at three medical intensive care units of a university hospital.

Results

The main causes of hypoxic hepatitis were low cardiac output and septic shock, and most patients (74%) had more than one underlying factor. Peak aspartate transaminase (P = 0.02), lactate dehydrogenase (P = 0.03), INR (P < 0.001) and lactate (P < 0.01) were higher in non-survivors. Prolonged duration of HH caused higher overall mortality rate (P = 0.03). INR > 2 (P = 0.02), septic shock (P = 0.01) and SOFA score >10 (P = 0.04) were risk factors of mortality in the regression model.

Conclusions

Hypoxic hepatitis is the consequence of multiorgan injury. Outcome is influenced by the severity of liver impairment and the etiology and severity of the basic disease.

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Abbreviations

HH:

Hypoxic hepatitis

ICU:

Intensive care unit

AST:

Serum aspartate transaminase level

ALT:

Serum alanine transaminase level

LDH:

Lactate dehydrogenase level

INR:

International normalized ratio

SAPS:

Simplified acute physiology score

SOFA:

Sequential organ failure assessment

IQR:

Interquartile range

CI:

Confidence interval

References

  1. Kramer L, Jordan B, Druml W, Bauer P, Metnitz PG (2007) Incidence and prognosis of early hepatic function in critically ill patients—a prospective multicenter study. Crit Care Med 35:1099–1104

    PubMed  Article  Google Scholar 

  2. Fuhrmann V, Madl C, Mueller C, Holzinger U, Kitzberger R, Funk G, Schenk P (2006) Hepatopulmonary syndrome in patients with hypoxic hepatitis. Gastroenterology 131:69–75

    PubMed  Article  Google Scholar 

  3. American Gastroenterological Association (2002) American Gastroenterological Association medical position statement: evaluation of liver chemistry tests. Gastroenterology 123:1364–1366

    Article  CAS  Google Scholar 

  4. Henrion J, Schapira M, Luwaert R, Colin L, Delannoy A, Heller FR (2003) Hypoxic hepatitis. Clinical and hemodynamic study in 142 consecutive cases. Medicine (Baltimore) 82:392–406

    Article  Google Scholar 

  5. Whitehead MW, Hawkes ND, Hainsworth I, Kingham JG (1999) A prospective study of the causes of notably raised aspartate aminotransferase of liver origin. Gut 45:129–133

    PubMed  CAS  Article  Google Scholar 

  6. Johnson RD, O′Connor C, Kerr RM (1995) Extreme serum elevations of aspartate aminotransferase. Am J Gastroenterol 90:1244–1245

    PubMed  CAS  Google Scholar 

  7. Gibson PR, Dudely F (1984) Ischemic hepatitis: clinical features, diagnosis and prognosis. Aust N Z J Med 14:822–825

    PubMed  CAS  Google Scholar 

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

    PubMed  Article  CAS  Google Scholar 

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

    PubMed  Article  Google Scholar 

  10. Seeto RK, Fenn B, Rockey DC (2000) Ischemic hepatitis: clinical presentation and pathogenesis. Am J Med 109:109–113

    PubMed  Article  CAS  Google Scholar 

  11. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M, Early Goal-Directed Therapy Collaborative Group (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345:1368–1377

    PubMed  Article  CAS  Google Scholar 

  12. Kumar A, Roberts D, Wood KE, Light B, Parillo JE, Sharma S, Suppes S, Feinstein D, Zanotti S, Taiberg L, Gurka D, Kumar A, Cheang M (2006) Duration of hypotension prior to initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 34:1589–1596

    PubMed  Article  Google Scholar 

  13. Topalian S, Ginsberg F, Parrillo JE (2008) Cardiogenic shock. Crit Care Med 36(Suppl):S66–S74

    PubMed  Article  Google Scholar 

  14. Schneeweiss B, Pammer J, Ratheiser K, Schneider B, Madl C, Kramer L, Kranz A, Ferenci P, Druml W, Grimm G (1993) Energy metabolism in acute hepatic failure. Gastroenterology 105:1515–1521

    PubMed  CAS  Google Scholar 

  15. Hickman PE, Potter J (1990) Mortality associated with ischemic hepatitis. Aust N Z J Med 20:32–34

    PubMed  CAS  Google Scholar 

  16. Goldberg RJ, Samad N, Yarzebski J, Gurwitz J, Bigelow C, Gore JM (1999) Temporal trends in cardiogenic shock complicating acute myocardial infarction. N Engl J Med 340:1162–1168

    PubMed  Article  CAS  Google Scholar 

  17. Califf RM, Bengtson J (1994) Cardiogenic shock. N Engl J Med 330:1724–1730

    PubMed  Article  CAS  Google Scholar 

  18. American College of Chest Physicians (Society of Critical Care Medicine Consensus Conference) (1992) Definition of sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20:864–874

    Google Scholar 

  19. Van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R (2001) Intensive insulin therapy in critically ill patients. N Engl J Med 345:1359–1367

    PubMed  Article  Google Scholar 

  20. Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, Moerer O, Gruendling M, Oppert M, Grond S, Olthoff D, Jaschinski U, John S, Rossaint R, Welte T, Schaefer M, Kern P, Kuhnt E, Kiehntopf M, Hartog C, Natanson C, Loeffler M, Reinhart K, German Competence Network Sepsis (SepNet) (2008) Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 358:125–139

    PubMed  Article  CAS  Google Scholar 

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

    PubMed  Article  CAS  Google Scholar 

  22. Malinchoc M, Kamath P, Gordon FD, Peine CJ, Rank J, ter Borg PC (2000) A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology 31:864–871

    PubMed  Article  CAS  Google Scholar 

  23. Polson J, Lee WM, American Association for the Study of Liver disease (2005) AASLD position paper: the management of acute liver failure. Hepatology 41:1179–1197

    PubMed  Article  Google Scholar 

  24. Peralta C, Perales J, Bartrons R, Mitchell C, Gilgenkrantz H, Xaus C, Prats N, Fernandez N, Gelpi E, Panes J, Rosello-Catafau J (2002) The combination of ischemic preconditioning and liver Bcl-2 over expression is a suitable strategy to prevent liver and lung damage after hepatic ischemia-reperfusion. Am J Pathol 160:2111–2122

    PubMed  CAS  Google Scholar 

  25. Nielsen VG, Tan S, Baird MS, Samuelson PN, McCammon AT, Parks DA (1997) Xanthine oxidase mediates myocardial injury after hepatoenteric ischemia-reperfusion. Crit Care Med 25:1044–1050

    PubMed  Article  CAS  Google Scholar 

  26. Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, Van Wijngaerden E, Bobbaers H, Bouillon R (2006) Intensive insulin therapy in the medical ICU. N Engl J Med 354:449–461

    PubMed  Article  Google Scholar 

  27. Stravitz RT, Kramer A, Davern T, Shaikh O, Caldwell SH, Mehta RL, Blei AT, Fontana RJ, McGuire BM, Rossaro L, Smith AD, Lee WM, Acute Liver Failure Study Group (2007) Intensive care of patients with acute liver failure: Recommendations of the U.S. Acute Liver Failure Study Group. Crit Care Med 35:2498–2508

    PubMed  Article  Google Scholar 

  28. Dunn G, Hayes P, Breen KJ (1973) The liver in congestive heart failure: a review. Am J Med Sci 265:174–189

    PubMed  Article  CAS  Google Scholar 

  29. Henrion J, Descamps O, Luwaert R, Schapira M, Parfonry A, Heller F (1994) Hypoxic hepatitis in patients with cardiac failure: incidence in a coronary care unit and measurement of hepatic blood flow. J Hepatol 21:696–703

    PubMed  Article  CAS  Google Scholar 

  30. Myers R, Cerini R, Sayegh R, Moreau R, Degott C, Lebrec D, Lee SS (2003) Cardiac hepatopathy: clinical, hemodynamic, and histologic characteristics and correlations. Hepatology 37:393–400

    PubMed  Article  Google Scholar 

  31. Sakka S, von Hout N (2006) Relation between indocyanine green clearance (ICG) plasma disappearance rate and ICG blood clearance in critically ill patients. Intensive Care Med 32:766–769

    PubMed  Article  CAS  Google Scholar 

  32. Sakka S, Koeck H, Meier-Hellmann A (2004) Measurement of indocyanine green plasma disappearance rate by two different dosages. Intensive Care Med 30:506–509

    PubMed  Article  Google Scholar 

  33. Sakka S, Reinhart K, Meier-Hellmann A (2000) Comparison of invasive and noninvasive measurements of indocyanine green plasma disappearance rate in critically ill patients with mechanical ventilation and stable hemodynamics. Intensive Care Med 26:1553–1556

    PubMed  Article  CAS  Google Scholar 

  34. Kneidinger N, Fuhrmann V, Kitzberger R, Warszawska J, Holzinger U, Lindner G, Schenk P, Locker G, Heinz G, Madl C (2007) Intensive Care Med 33(2):0188

    Google Scholar 

  35. Vincent JL, Moreno R, Takala J, Willatts S, De Mendoca A, Bruining H, Reinhart CK, Suter PM, Thijs LG (1996) The SOFA (sepsis-related organ assessment) score to describe organ dysfunction/failure. Intensive Care Med 22:707–710

    PubMed  Article  CAS  Google Scholar 

  36. Aninat C, Seguin P, Descheemaeker P-N, Morel F, Malledant Y, Guillouzo A (2008) Catecholamines induce an inflammatory response in human hepatocytes. Crit Care Med 36:848–854

    PubMed  Article  CAS  Google Scholar 

  37. Carvalho F, Remiao F, Soares ME, Catarino R, Queiroz G, Bastos ML (1997) d-Amphetamine-induced hepatotoxicity: possible contribution of catecholamines and hyperthermia to the effect studied in isolated rat hepatocytes. Arch Toxicol 71:429–436

    PubMed  Article  CAS  Google Scholar 

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Acknowledgments

There was no financial support for this study.

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Corresponding author

Correspondence to Valentin Fuhrmann.

Additional information

The study was performed at the intensive care units 13H1, 13H3 and 13I2 of the Medical University of Vienna.

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Fuhrmann, V., Kneidinger, N., Herkner, H. et al. Hypoxic hepatitis: underlying conditions and risk factors for mortality in critically ill patients. Intensive Care Med 35, 1397–1405 (2009). https://doi.org/10.1007/s00134-009-1508-2

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  • DOI: https://doi.org/10.1007/s00134-009-1508-2

Keywords

  • Ischemic hepatitis
  • Shock liver
  • Risk factors
  • Hypoglycemia