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Acute liver failure in children: Etiology and evaluation

Author
Robert H Squires, Jr, MD, FAAP
Section Editor
Elizabeth B Rand, MD
Deputy Editor
Alison G Hoppin, MD

INTRODUCTION

Pediatric acute liver failure (PALF) is a complex, rapidly progressive clinical syndrome that is the final common pathway for many disparate conditions, some known and others yet to be identified [1-3]. The estimated frequency of acute liver failure (ALF) in all age groups in the United States is about 17 cases per 100,000 population per year, but the frequency in children is unknown. PALF accounts for 10 to 15 percent of pediatric liver transplants performed in the United States annually.

PALF is a rapidly evolving clinical condition. There are no adequately powered studies to inform diagnostic algorithms, to assess markers of disease severity and trajectory, or to guide decisions about liver transplantation (LT). The clinician must construct an individualized diagnostic approach and management strategy. Management requires a multidisciplinary team involving the hepatologist, critical care specialist, and liver transplant surgeon.

The pressing clinical questions faced when children with PALF first present are:

Does the patient have a condition that is treatable?

What is the risk of deterioration or improvement on each day the child is alive with his or her native liver?

                               

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Literature review current through: Nov 2016. | This topic last updated: Wed Dec 02 00:00:00 GMT 2015.
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References
Top
  1. Squires RH Jr, Shneider BL, Bucuvalas J, et al. Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group. J Pediatr 2006; 148:652.
  2. Squires RH Jr. Acute liver failure in children. Semin Liver Dis 2008; 28:153.
  3. Squires RH, Alonso EM. Acute liver failure in children. In: Liver Disease in Children, 4th ed, Suchy FJ, Sokol RJ, Balistreri WF (Eds), Cambridge University Press, New York 2012.
  4. Heubi JE, Barbacci MB, Zimmerman HJ. Therapeutic misadventures with acetaminophen: hepatoxicity after multiple doses in children. J Pediatr 1998; 132:22.
  5. Watkins PB, Seeff LB. Drug-induced liver injury: summary of a single topic clinical research conference. Hepatology 2006; 43:618.
  6. Rivera-Penera T, Gugig R, Davis J, et al. Outcome of acetaminophen overdose in pediatric patients and factors contributing to hepatotoxicity. J Pediatr 1997; 130:300.
  7. Leonis MA, Alonso EM, Im K, et al. Chronic acetaminophen exposure in pediatric acute liver failure. Pediatrics 2013; 131:e740.
  8. Abboud G, Kaplowitz N. Drug-induced liver injury. Drug Saf 2007; 30:277.
  9. Reuben A, Koch DG, Lee WM, Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology 2010; 52:2065.
  10. Molleston JP, Fontana RJ, Lopez MJ, et al. Characteristics of idiosyncratic drug-induced liver injury in children: results from the DILIN prospective study. J Pediatr Gastroenterol Nutr 2011; 53:182.
  11. Stickel F, Patsenker E, Schuppan D. Herbal hepatotoxicity. J Hepatol 2005; 43:901.
  12. Narkewicz MR, Dell Olio D, Karpen SJ, et al. Pattern of diagnostic evaluation for the causes of pediatric acute liver failure: an opportunity for quality improvement. J Pediatr 2009; 155:801.
  13. Hennes EM, Zeniya M, Czaja AJ, et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology 2008; 48:169.
  14. Mileti E, Rosenthal P, Peters MG. Validation and modification of simplified diagnostic criteria for autoimmune hepatitis in children. Clin Gastroenterol Hepatol 2012; 10:417.
  15. McClain K, Gehrz R, Grierson H, et al. Virus-associated histiocytic proliferations in children. Frequent association with Epstein-Barr virus and congenital or acquired immunodeficiencies. Am J Pediatr Hematol Oncol 1988; 10:196.
  16. Parizhskaya M, Reyes J, Jaffe R. Hemophagocytic syndrome presenting as acute hepatic failure in two infants: clinical overlap with neonatal hemochromatosis. Pediatr Dev Pathol 1999; 2:360.
  17. Schwarz KB, Dell Olio D, Lobritto SJ, et al. Analysis of viral testing in nonacetaminophen pediatric acute liver failure. J Pediatr Gastroenterol Nutr 2014; 59:616.
  18. Henter JI, Horne A, Aricó M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007; 48:124.
  19. DiPaola F, Grimley M, Bucuvalas J. Pediatric acute liver failure and immune dysregulation. J Pediatr 2014; 164:407.
  20. Pan X, Kelly S, Melin-Aldana H, et al. Novel mechanism of fetal hepatocyte injury in congenital alloimmune hepatitis involves the terminal complement cascade. Hepatology 2010; 51:2061.
  21. Hanchard NA, Shchelochkov OA, Roy A, et al. Deoxyguanosine kinase deficiency presenting as neonatal hemochromatosis. Mol Genet Metab 2011; 103:262.
  22. Rand EB, Karpen SJ, Kelly S, et al. Treatment of neonatal hemochromatosis with exchange transfusion and intravenous immunoglobulin. J Pediatr 2009; 155:566.
  23. Helbling D, Buchaklian A, Wang J, et al. Reduced mitochondrial DNA content and heterozygous nuclear gene mutations in patients with acute liver failure. J Pediatr Gastroenterol Nutr 2013; 57:438.
  24. Sundaram SS, Alonso EM, Narkewicz MR, et al. Characterization and outcomes of young infants with acute liver failure. J Pediatr 2011; 159:813.
  25. Patterson M. Niemann-Pick disease type C. GeneReviews. Available at: http://www.ncbi.nlm.nih.gov/books/NBK1296/ (Accessed on April 18, 2012).
  26. Lee WS, Sokol RJ. Mitochondrial hepatopathies: advances in genetics, therapeutic approaches, and outcomes. J Pediatr 2013; 163:942.
  27. Shneider BL, Rinaldo P, Emre S, et al. Abnormal concentrations of esterified carnitine in bile: a feature of pediatric acute liver failure with poor prognosis. Hepatology 2005; 41:717.
  28. Korman JD, Volenberg I, Balko J, et al. Screening for Wilson disease in acute liver failure: a comparison of currently available diagnostic tests. Hepatology 2008; 48:1167.
  29. Moreira-Silva SF, Frauches DO, Almeida AL, et al. Acute liver failure in children: observations in Vitória, Espírito Santo State, Brazil. Rev Soc Bras Med Trop 2002; 35:483.
  30. Bartholomeusz A, Locarnini S. Hepatitis B virus mutants and fulminant hepatitis B: fitness plus phenotype. Hepatology 2001; 34:432.
  31. Farci P, Alter HJ, Shimoda A, et al. Hepatitis C virus-associated fulminant hepatic failure. N Engl J Med 1996; 335:631.
  32. Liang TJ, Jeffers L, Reddy RK, et al. Fulminant or subfulminant non-A, non-B viral hepatitis: the role of hepatitis C and E viruses. Gastroenterology 1993; 104:556.
  33. Poddar U, Thapa BR, Prasad A, Singh K. Changing spectrum of sporadic acute viral hepatitis in Indian children. J Trop Pediatr 2002; 48:210.
  34. Hamid SS, Jafri SM, Khan H, et al. Fulminant hepatic failure in pregnant women: acute fatty liver or acute viral hepatitis? J Hepatol 1996; 25:20.
  35. Khuroo MS, Teli MR, Skidmore S, et al. Incidence and severity of viral hepatitis in pregnancy. Am J Med 1981; 70:252.
  36. Verma A, Dhawan A, Zuckerman M, et al. Neonatal herpes simplex virus infection presenting as acute liver failure: prevalent role of herpes simplex virus type I. J Pediatr Gastroenterol Nutr 2006; 42:282.
  37. Härmä M, Höckerstedt K, Lautenschlager I. Human herpesvirus-6 and acute liver failure. Transplantation 2003; 76:536.
  38. Tung J, Hadzic N, Layton M, et al. Bone marrow failure in children with acute liver failure. J Pediatr Gastroenterol Nutr 2000; 31:557.
  39. Karetnyi YV, Beck PR, Markin RS, et al. Human parvovirus B19 infection in acute fulminant liver failure. Arch Virol 1999; 144:1713.
  40. Lee WM, Brown KE, Young NS, et al. Brief report: no evidence for parvovirus B19 or hepatitis E virus as a cause of acute liver failure. Dig Dis Sci 2006; 51:1712.
  41. Phillips MJ, Blendis LM, Poucell S, et al. Syncytial giant-cell hepatitis. Sporadic hepatitis with distinctive pathological features, a severe clinical course, and paramyxoviral features. N Engl J Med 1991; 324:455.
  42. Listernick R. Liver failure in a 2-day-old infant. Pediatr Ann 2004; 33:10.
  43. Lo JO, Harrison RA, Hunter AJ. Syphilitic hepatitis resulting in fulminant hepatic failure requiring liver transplantation. J Infect 2007; 54:e115.
  44. Stevens FM, McLoughlin RM. Is coeliac disease a potentially treatable cause of liver failure? Eur J Gastroenterol Hepatol 2005; 17:1015.
  45. Umemura T, Tanaka E, Ostapowicz G, et al. Investigation of SEN virus infection in patients with cryptogenic acute liver failure, hepatitis-associated aplastic anemia, or acute and chronic non-A-E hepatitis. J Infect Dis 2003; 188:1545.
  46. James LP, Alonso EM, Hynan LS, et al. Detection of acetaminophen protein adducts in children with acute liver failure of indeterminate cause. Pediatrics 2006; 118:e676.
  47. Rivera-Penera T, Moreno J, Skaff C, et al. Delayed encephalopathy in fulminant hepatic failure in the pediatric population and the role of liver transplantation. J Pediatr Gastroenterol Nutr 1997; 24:128.
  48. Lee WS, McKiernan P, Kelly DA. Etiology, outcome and prognostic indicators of childhood fulminant hepatic failure in the United kingdom. J Pediatr Gastroenterol Nutr 2005; 40:575.
  49. Stravitz RT, Lefkowitch JH, Fontana RJ, et al. Autoimmune acute liver failure: proposed clinical and histological criteria. Hepatology 2011; 53:517.