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Chapter 4 - Acute liver failure in children

from Section I - Pathophysiology of pediatric liver disease

Published online by Cambridge University Press:  05 March 2014

Robert H. Squires
Affiliation:
Pediatric Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Pittsburgh of UPMC, and Professor of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA
Estella M. Alonso
Affiliation:
Northwestern University, Chicago; Department of Gastroenterology, Hepatology and Nutrition, Children’s Memorial Hospital, Chicago, IL, USA
Frederick J. Suchy
Affiliation:
University of Colorado Medical Center
Ronald J. Sokol
Affiliation:
University of Colorado Medical Center
William F. Balistreri
Affiliation:
University of Cincinnati College of Medicine
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Summary

Introduction

Pediatric acute liver failure (ALF) is not a single diagnosis. Rather, pediatric ALF 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 [1,2]. The estimated frequency of ALF in all age groups in the USA is about 17 cases per 100000 population per year, but the frequency in children is unknown. In the USA, ALF accounts for 10–15% of pediatric liver transplants performed annually. Management requires a multidisciplinary team involving the hepatologist, critical care specialist, and liver transplant surgeon.

Acute liver failure is a rapidly evolving clinical condition. The absence of adequately powered studies to inform diagnostic algorithms, to assess markers of disease severity and trajectory, and to guide liver transplant decisions transfers a significant burden to the clinician. Constructing a diagnostic approach and individualized management strategy that may include the decision to pursue liver transplantation is challenging. There are a number of pressing clinical questions faced when children with pediatric ALF first present. 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/her native liver? Is a living related or deceased liver transplant necessary for patient survival? Is full recovery possible without a liver transplant? Are associated morbidities recoverable or irreversible?

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Publisher: Cambridge University Press
Print publication year: 2014

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References

Squires, RH, 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;148:652–658.CrossRefGoogle ScholarPubMed
Squires, RH. Acute liver failure in children. Semin Liver Dis 2008;28:153–166.CrossRefGoogle ScholarPubMed
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;24:128–134.CrossRefGoogle ScholarPubMed
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;40:575–581.CrossRefGoogle ScholarPubMed
Heubi, JE, Barbacci, MB, Zimmerman, HJ. Therapeutic misadventures with acetaminophen: hepatoxicity after multiple doses in children. J Pediatr 1998;132:22–27.CrossRefGoogle ScholarPubMed
Watkins, PB, Seeff, LB. Drug-induced liver injury: summary of a single topic clinical research conference. Hepatology 2006;43:618–631.CrossRefGoogle ScholarPubMed
Rumack, BH. Acetaminophen overdose in children and adolescents. Pediatr Clin North Am. 1986;33:691–701.CrossRefGoogle ScholarPubMed
Rivera-Penera, T, Gugig, R, Davis, J, et al. Outcome of acetaminophen overdose in pediatric patients and factors contributing to hepatotoxicity. J Pediatr 1997;130:300–304.CrossRefGoogle ScholarPubMed
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–e681.CrossRefGoogle ScholarPubMed
Larson, AM, Polson, J, Fontana, RJ, et al. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology 2005;42:1364–1372.CrossRefGoogle ScholarPubMed
Abboud, G, Kaplowitz, N. Drug-induced liver injury. Drug Saf 2007;30:277–294.CrossRefGoogle ScholarPubMed
Reuben, A, Koch, DG, Lee, WM. Drug-induced acute liver failure: results of a US multicenter, prospective study. Hepatology 2010;52:2065–2076.CrossRefGoogle Scholar
Stickel, F, Patsenker, E, Schuppan, D. Herbal hepatotoxicity. J Hepatol 2005;43:901–910.CrossRefGoogle ScholarPubMed
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;155:801–806.CrossRefGoogle Scholar
Stravitz, RT, Lefkowitch, JH, Fontana, RJ, et al. Autoimmune acute liver failure: proposed clinical and histological criteria. Hepatology 2011;53:517–526.CrossRefGoogle ScholarPubMed
Henter, JI, Horne, A, Arico, M, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007;48:124–131.CrossRefGoogle ScholarPubMed
Pan, X, Kelly, S, Melin-Aldana, H, Malladi, P, Whitington, PF. Novel mechanism of fetal hepatocyte injury in congenital alloimmune hepatitis involves the terminal complement cascade. Hepatology 2010;51:2061–2068.CrossRefGoogle ScholarPubMed
Rand, EB, Karpen, SJ, Kelly, S, et al. Treatment of neonatal hemochromatosis with exchange transfusion and intravenous immunoglobulin. J Pediatr 2009;155:566–571.CrossRefGoogle ScholarPubMed
Sundaram, SS, Alonso, EM, Narkewicz, MR, Zhang, S, Squires, RH. Characterization and outcomes of young infants with acute liver failure. J Pediatr 2011;159:813–818.CrossRefGoogle ScholarPubMed
Sokal, EM, Sokol, R, Cormier, V, et al. Liver transplantation in mitochondrial respiratory chain disorders. Eur J Pediatr 1999;158(Suppl 2):S81–S84.CrossRefGoogle ScholarPubMed
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;41:717–721.CrossRefGoogle ScholarPubMed
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;48:1167–1174.CrossRefGoogle ScholarPubMed
Moreira-Silva, SF, Frauches, DO, Almeida, AL, Mendonca, HF, Pereira, FE. Acute liver failure in children: observations in Vitoria, Espirito Santo State, Brazil. Rev Soc Bras Med Trop 2002;35:483–486.CrossRefGoogle Scholar
Bartholomeusz, A, Locarnini, S. Hepatitis B virus mutants and fulminant hepatitis B: fitness plus phenotype. Hepatology 2001;34:432–435.CrossRefGoogle ScholarPubMed
Farci, P, Alter, HJ, Shimoda, A, et al. Hepatitis C virus-associated fulminant hepatic failure. N Engl J Med 1996;335:631–634.CrossRefGoogle ScholarPubMed
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;104:556–562.CrossRefGoogle ScholarPubMed
Poddar, U, Thapa, BR, Prasad, A, Singh, K. Changing spectrum of sporadic acute viral hepatitis in Indian children. J Trop Pediatr 2002;48:210–213.CrossRefGoogle ScholarPubMed
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;42:282–286.CrossRefGoogle ScholarPubMed
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;324:455–460.CrossRefGoogle ScholarPubMed
Stevens, FM, McLoughlin, RM. Is coeliac disease a potentially treatable cause of liver failure? Eur J Gastroenterol Hepatol 2005;17:1015–1017.CrossRefGoogle ScholarPubMed
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;188:1545–1552.CrossRefGoogle ScholarPubMed
Racanelli, V, Rehermann, B. The liver as an immunological organ. Hepatology 2006;43(Suppl 1):S54–S62.CrossRefGoogle ScholarPubMed
Gao, B, Jeong, WI, Tian, Z. Liver: an organ with predominant innate immunity. Hepatology 2008;47:729–736.CrossRefGoogle ScholarPubMed
Crispe, IN. The liver as a lymphoid organ. Annu Rev Immunol 2009;27:147–163.CrossRefGoogle ScholarPubMed
Paust, S, Senman, B, von Andrian, UH. Adaptive immune responses mediated by natural killer cells. Immunol Rev 2010;235:286–296.CrossRefGoogle ScholarPubMed
Gunawan, BK, Liu, ZX, Han, D, et al. c-Jun N-terminal kinase plays a major role in murine acetaminophen hepatotoxicity. Gastroenterology 2006;131:165–178.CrossRefGoogle Scholar
Kon, K, Kim, JS, Jaeschke, H, Lemasters, JJ. Mitochondrial permeability transition in acetaminophen-induced necrosis and apoptosis of cultured mouse hepatocytes. Hepatology 2004;40:1170–1179.CrossRefGoogle ScholarPubMed
Liu, ZX, Han, D, Gunawan, B, Kaplowitz, N. Neutrophil depletion protects against murine acetaminophen hepatotoxicity. Hepatology 2006;43:1220–1230.CrossRefGoogle ScholarPubMed
Kofman, AV, Morgan, G, Kirschenbaum, A, et al. Dose- and time-dependent oval cell reaction in acetaminophen-induced murine liver injury. Hepatology 2005;41:1252–1261.CrossRefGoogle ScholarPubMed
Begriche, K, Massart, J, Robin, MA, Borgne-Sanchez, A, Fromenty, B. Drug-induced toxicity on mitochondria and lipid metabolism: mechanistic diversity and deleterious consequences for the liver. J Hepatol 2011;54:773–794.CrossRefGoogle ScholarPubMed
Karlson-Stiber, C, Persson, H. Cytotoxic fungi: an overview. Toxicon 2003;42:339–349.CrossRefGoogle ScholarPubMed
Antoniades, CG, Berry, PA, Wendon, JA, Vergani, D. The importance of immune dysfunction in determining outcome in acute liver failure. J Hepatol 2008;49:845–861.CrossRefGoogle ScholarPubMed
Eksteen, B, Afford, SC, Wigmore, SJ, Holt, AP, Adams, DH. Immune-mediated liver injury. Semin Liver Dis 2007;27:351–366.CrossRefGoogle ScholarPubMed
Adams, DH, Ju, C, Ramaiah, SK, Uetrecht, J, Jaeschke, H. Mechanisms of immune-mediated liver injury. Toxicol Sci 2010;115:307–321.CrossRefGoogle ScholarPubMed
Mi, Q, Li, NY, Ziraldo, C, et al. Translational systems biology of inflammation: potential applications to personalized medicine. Per Med 2010;7:549–559.CrossRefGoogle ScholarPubMed
Michalopoulos, GK. Liver regeneration. J Cell Physiol 2007;213:286–300.CrossRefGoogle ScholarPubMed
Ichai, P, Roque-Afonso, AM, Sebagh, M, et al. Herpes simplex virus-associated acute liver failure: A difficult diagnosis with a poor prognosis. Liver Transplant 2005;11:1550–1555.CrossRefGoogle ScholarPubMed
Alonso, EM, Sokol, RJ, Hart, J, et al. Fulminant hepatitis associated with centrilobular hepatic necrosis in young children. J Pediatr 1995;127:888–894.CrossRefGoogle ScholarPubMed
Ussery, XT, Henar, EL, Black, DD, Berger, S, Whitington, PF. Acute liver injury after protracted seizures in children. J Pediatr Gastroenterol Nutr 1989;9:421–425.CrossRefGoogle ScholarPubMed
Whitington, PF, Alonso, AE. Fulminant hepatitis and acute liver failure. In Kelly, DA (ed.) Paediatric Liver Disease. Oxford: Blackwell, 2003, pp. 107–126.Google Scholar
Wendon, J, Lee, W. Encephalopathy and cerebral edema in the setting of acute liver failure: pathogenesis and management. Neurocrit Care 2008;9:97–102.CrossRefGoogle ScholarPubMed
Stravitz, RT, Kramer, AH, Davern, T, et al. Intensive care of patients with acute liver failure: recommendations of the US Acute Liver Failure Study Group. Crit Care Med 2007;35:2498–2508.CrossRefGoogle Scholar
Shawcross, DL, Wendon, JA. The neurological manifestations of acute liver failure. Neurochem Int 2012;60:662–671.CrossRefGoogle ScholarPubMed
Hadzic, N, Height, S, Ball, S, et al. Evolution in the management of acute liver failure-associated aplastic anaemia in children: a single centre experience. J Hepatol 2008;48:68–73.CrossRefGoogle ScholarPubMed
Liu, E, MacKenzie, T, Dobyns, EL, et al. Characterization of acute liver failure and development of a continuous risk of death staging system in children. J Hepatol 2006;44:134–141.CrossRefGoogle ScholarPubMed
Lu, BR, Zhang, S, Narkewicz, MR, et al. Evaluation of the liver injury scoring system to predict survival in a multinational study of pediatric acute liver failure. J Pediatr 2013;162:1010–1016.CrossRefGoogle Scholar
Alagoz, O, Maillart, L, Schaefer, A, Roberts, MS. Determining the acceptance of cadaveric livers using an implicit model of the waiting list. Operations Res 2007;55:24–36.CrossRefGoogle Scholar
Baliga, P, Alvarez, S, Lindblad, A, Zeng, L. Posttransplant survival in pediatric fulminant hepatic failure: the SPLIT experience. Liver Transplant 2004;10:1364–1371.CrossRefGoogle ScholarPubMed
Mack, CL, Ferrario, M, Abecassis, M, et al. Living donor liver transplantation for children with liver failure and concurrent multiple organ system failure. Liver Transplant 2001;7:890–895.CrossRefGoogle ScholarPubMed
Girlanda, R, Vilca-Melendez, H, Srinivasan, P, et al. Immunosuppression withdrawal after auxiliary liver transplantation for acute liver failure. Transplant Proc 2005;37:1720–1721.CrossRefGoogle ScholarPubMed
Soltys, KA, Soto-Gutierrez, A, Nagaya, M, et al. Barriers to the successful treatment of liver disease by hepatocyte transplantation. J Hepatol 2010;53:769–774.CrossRefGoogle ScholarPubMed
Psacharopoulos, HT, Mowat, AP, Davies, M, et al. Fulminant hepatic failure in childhood: an analysis of 31 cases. Arch Dis Child 1980;55:252–258.CrossRefGoogle ScholarPubMed
Soltys, KA, Mazariegos, GV, Squires, RH, Sindhi, RK, Anand, R. Late graft loss or death in pediatric liver transplantation: an analysis of the SPLIT database. Am J Transplant 2007;7:2165–2171.CrossRefGoogle ScholarPubMed

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  • Acute liver failure in children
    • By Robert H. Squires, Pediatric Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Pittsburgh of UPMC, and Professor of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA, Estella M. Alonso, Northwestern University, Chicago; Department of Gastroenterology, Hepatology and Nutrition, Children’s Memorial Hospital, Chicago, IL, USA
  • Edited by Frederick J. Suchy, University of Colorado Medical Center, Ronald J. Sokol, University of Colorado Medical Center, William F. Balistreri
  • Book: Liver Disease in Children
  • Online publication: 05 March 2014
  • Chapter DOI: https://doi.org/10.1017/CBO9781139012102.005
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  • Acute liver failure in children
    • By Robert H. Squires, Pediatric Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Pittsburgh of UPMC, and Professor of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA, Estella M. Alonso, Northwestern University, Chicago; Department of Gastroenterology, Hepatology and Nutrition, Children’s Memorial Hospital, Chicago, IL, USA
  • Edited by Frederick J. Suchy, University of Colorado Medical Center, Ronald J. Sokol, University of Colorado Medical Center, William F. Balistreri
  • Book: Liver Disease in Children
  • Online publication: 05 March 2014
  • Chapter DOI: https://doi.org/10.1017/CBO9781139012102.005
Available formats
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Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

  • Acute liver failure in children
    • By Robert H. Squires, Pediatric Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Pittsburgh of UPMC, and Professor of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA, Estella M. Alonso, Northwestern University, Chicago; Department of Gastroenterology, Hepatology and Nutrition, Children’s Memorial Hospital, Chicago, IL, USA
  • Edited by Frederick J. Suchy, University of Colorado Medical Center, Ronald J. Sokol, University of Colorado Medical Center, William F. Balistreri
  • Book: Liver Disease in Children
  • Online publication: 05 March 2014
  • Chapter DOI: https://doi.org/10.1017/CBO9781139012102.005
Available formats
×