Metabolic Brain Disease

, Volume 28, Issue 1, pp 7–10 | Cite as

Acute liver failure and the brain: a look through the crystal ball

  • Jennifer M. Ryan
  • Thomas Tranah
  • Ragai R. Mitry
  • Julia A. Wendon
  • Debbie L. Shawcross
Review Article

Abstract

Over the past 35 years, the outlook for a patient presenting with acute liver failure (ALF) has changed beyond all recognition. A patient presenting in 1984 had an 80 % likelihood of succumbing to intracranial hypertension. Today due to dramatic improvements in intensive care in dedicated liver transplant units, this has been reduced to just 20 %. Prompt fluid resuscitation, empirical treatment for sepsis and standardised management protocols that include early intubation and high flow hemofiltration for ammonia removal, limit the numbers of patients who die from the sequelae of cerebral edema and ALF. With the evolution and development of bedside prognostic markers that will include personalised genomic, metabonomic and immune profiling, rationalisation of grafts to those who are not predicted to survive is likely to further minimise the number of grafts utilised. Furthermore, in those patients with a dismal prognosis, the use of plasmapheresis, immunomodulatory therapies, biological liver support systems and hepatocyte transplantation offer a potential bridge until the injured liver can begin to regenerate avoiding transplantation and life-long immunosuppressant therapy.

Keywords

Acute liver failure Hepatic encephalopathy Intracranial hypertension Brain edema Personalised medicine Immune profiling 

Notes

Acknowledgement

Dr Shawcross is funded by a 5 year UK Department of Health HEFCE Clinical Senior Lectureship.

References

  1. Acharya S, Bhatia V, Sreenivas V, Khanal S, Panda S (2009) Efficacy of L-Ornithine L-Aspartate in acute liver failure: a double-blind, randomised, placebo-controlled study. Gastroenterology 136(7):2159–2168PubMedCrossRefGoogle Scholar
  2. Barba I, Chatauret N, Garcia-Dorado D, Cordoba J (2008) A 1H nuclear magnetic resonance-based metabonomic approach for grading hepatic encephalopathy and monitoring the effects of therapeutic hypothermia in rats. Liver Int 28(8):1141–1148PubMedCrossRefGoogle Scholar
  3. Bernal W, Hall C, Karvellas C, Auzinger G, Sizer E, Wendon J (2007) Arterial ammonia and clinical risk factors for encephalopathy and intracranial hypertension in acute liver failure. Hepatology 46(6):1844–1852PubMedCrossRefGoogle Scholar
  4. Bernal W, Auzinger G, Sizer E, Wendon J (2008) Intensive care management for acute liver failure. Semin Liver Dis 28(2):188–200PubMedCrossRefGoogle Scholar
  5. Bernal W, Hyyrylainen A, Gera A, Audimoolam V, Heaton N, Wendon J et al (2010) Evolution of natural history and treatment strategies in acute liver failure: lessons from a 35 year experiencein 3300 patients. [Abstract]. Hepatology 52(Supplement 4)Google Scholar
  6. Clemmesen J, Larsen F, Kondrup J, Hansen B, Ott P (1999) Cerebral herniation in patients with acute liver failure is correlated with arterial ammonia concentration. Hepatology 29:648–653PubMedCrossRefGoogle Scholar
  7. Dhawan A, Puppi J, Hughes RD, Mitry RR (2010) Hepatocyte transplantation: update and challenges ahead. Nat Rev Gastroenterol Hepatol 7(5):288–298PubMedCrossRefGoogle Scholar
  8. Ellis AJ, Wendon JA, Williams R (2000) Subclinical seizure activity and prophylactic phenytoin infusion in acute liver failure: a controlled clinical trial. Hepatology 32(3):536–541PubMedCrossRefGoogle Scholar
  9. Habibullah CM, Syed IH, Qamar A, Taher-Uz Z (1994) Human fetal hepatocyte transplantation in patients with fulminant hepatic failure. Transplant 58(8):951–952CrossRefGoogle Scholar
  10. Harrison PM, Wendon JA, Gimson AE, Alexander GJ, Williams R (1991) Improvement by N-acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. N Engl J Med 324:1852–1857PubMedCrossRefGoogle Scholar
  11. Jalan R, Olde Damink SW, Deutz NE, Hayes PC, Lee A (2004) Moderate hypothermia in patients with acute liver failure and uncontrolled intracranial hypertension. Gastroenterology 127(5):1338–1346PubMedCrossRefGoogle Scholar
  12. Kato M, Hughes R, Keays R, Williams R (1992) Electron microscopic study of brain capillaries in cerebral oedema from fulminant hepatic failure. Hepatology 15:1060–1066PubMedCrossRefGoogle Scholar
  13. Larsen FS, Adel HB, Pott F, Ejlersen E, Secher NH, Paulson OB et al (1996a) Dissociated cerebral vasoparalysis in acute liver failure. A hypothesis of gradual cerebral hyperaemia. J Hepatol 25(2):145–151PubMedCrossRefGoogle Scholar
  14. Larsen FS, Hansen BA, Ejlersen E, Secher NH, Clemmesen JO, Tygstrup N et al (1996b) Cerebral blood flow, oxygen metabolism and transcranial Doppler sonography during high-volume plasmapheresis in fulminant hepatic failure. Eur J Gastroenterol Hepatol 8(3):261–265PubMedCrossRefGoogle Scholar
  15. Larsen F, Murphy N, Bernal W, Bjerring P, Hauerberg A, Wendon J et al (2011) The prophylactic effect of mild hypothermia to prevent brain oedema in patients with acute liver failure: results of a multicentre randomised controlled trial. [Abstract]. J Hepatol 54(Supplement 1):S26CrossRefGoogle Scholar
  16. Lee WM, Hynan LS, Rossaro L et al (2009) Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology 137:856–864PubMedCrossRefGoogle Scholar
  17. Manakkat Vijay GK, Abeles RD, Ramage S, Riva A, Vergis N, Ryan J et al (2012) Neutrophil intracellular toll-like receptor (TLR9) expression serves as a biomarker that determines presence and severity of encephalopathy in acute liver failure and cirrhosis. [Abstract]. J Hepatol 56(Supplement 2):S102–S103CrossRefGoogle Scholar
  18. Martinez-Llordella M, Lozano JJ, Puig-Pey I, Orlando G, Tisone G, Lerut J et al (2008) Using transcriptional profiling to develop a diagnostic test of operational tolerance in liver transplant recipients. J Clin Invest 118(8):2845–2857PubMedGoogle Scholar
  19. Murphy N, Auzinger G, Bernel W, Wendon J (2004) The effect of hypertonic sodium chloride on intracranial pressure in patients with acute liver failure. Hepatology 39(2):464–470PubMedCrossRefGoogle Scholar
  20. Puglisi MA, Tesori V, Lattanzi W, Piscaglia AC, Gasbarrini GB, D’Ugo DM et al (2011) Therapeutic implications of mesenchymal stem cells in liver injury. J Biomed Biotechnol 2011:860578PubMedCrossRefGoogle Scholar
  21. Rolando N, Wade J, Davalos M, Wendon J, Philpott-Howard J, Williams R (2000a) The systemic inflammatory response syndrome in acute liver failure. Hepatology 32:734–739PubMedCrossRefGoogle Scholar
  22. Rolando N, Clapperton M, Wade J, Panetsos G, Mufti G, Williams R (2000b) Granulocyte colony-stimulating factor improves function of neutrophils from patients with acute liver failure. Eur J Gastroenterol Hepatol 12(10):1135–1140PubMedCrossRefGoogle Scholar
  23. Shawcross DL, Wendon JA (2011) The neurological manifestations of acute liver failure. Neurochem IntGoogle Scholar
  24. Thiel K, Proven A, Davies N, Leckie P, Frieg R, Storr M et al (2012) The development and testing of the University College London liver support device (ARSENEL): improvement in survival in paracetamol-induced acute liver failure pigs. [Abstract]. Gut 59(2)Google Scholar
  25. Vaquero J, Polson J, Chung C, Helenowski I, Schiodt FV, Reisch J et al (2003) Infection and the progression of hepatic encephalopathy in acute liver failure. Gastroenterology 125(3):755–764PubMedCrossRefGoogle Scholar
  26. Wendon JA, Harrison PM, Keays R, Williams R (1994) Cerebral blood flow and metabolism in fulminant liver failure. Hepatology 19:1407–1413PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Jennifer M. Ryan
    • 1
    • 2
  • Thomas Tranah
    • 1
  • Ragai R. Mitry
    • 1
  • Julia A. Wendon
    • 1
    • 2
  • Debbie L. Shawcross
    • 1
    • 2
  1. 1.Institute of Liver Studies, King’s College London School of Medicine at King’s College HospitalKing’s College HospitalDenmark HillUK
  2. 2.Liver Intensive Care UnitKing’s College HospitalDenmark HillUK

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