Pediatric Fulminant Hepatic Failure Workup
- Author: Hisham Nazer, MB, BCh, FRCP, , DTM&H; Chief Editor: Carmen Cuffari, MD more...
A range of laboratory studies is required to determine the etiology, severity, and prognosis in patients with fulminant hepatic failure (FHF). Liver biopsy is usually an essential procedure to consider in the management of FHF.
Liver Function Studies
Hepatic enzyme levels do not correlate well with the severity of the disease; they may be elevated, normal, or even decreased in patients with FHF. Levels are often markedly elevated in patients with metabolic disorders. With progressive necrosis of the liver, hepatic enzyme levels decrease.
Both direct and indirect serum bilirubin levels are usually elevated. Typically, conjugated hyperbilirubinemia is present.
Glucose level is decreased, especially in infants. Hyponatremia (see Serum Sodium), hyperkalemia (see Potassium), respiratory alkalosis, or metabolic acidosis (see Acid-Base Interpretation) may also be present.
Renal Function Studies
Prothrombin time (PT) is prolonged. However, administration of vitamin K typically has not been found to result in a satisfactory drop in prothrombin time (PT) in patients with FHF.
Tests for Viral Causes
Hepatitis A virus (HAV), hepatitis B virus (HBV; see Hepatitis B Test), hepatitis C virus (HCV; see Hepatitis C Test), hepatitis D virus (HDV), hepatitis E virus and many other viruses other than hepatitis also are recognized causes of FHF in childhood.
HBV is the most common cause of FHF in endemic areas. Presence of immunoglobulin M (IgM) antibody to HBV core antigen (IgM anti-HBcAg) in serum supports the diagnosis of acute HBV infection.
HAV infection is a recognized cause of FHF in individuals of all ages. Diagnosis of HAV infection is made by the presence of anti-HAV IgM in the patient’s serum. HCV infection is diagnosed with detection of anti-HCV antibody or HCV RNA in the serum. HDV is diagnosed by the presence of anti-HDV RNA in the serum.
Other causative viruses include Epstein-Barr virus, cytomegalovirus (CMV), herpesviruses, and adenoviruses.
Liver biopsy may contribute to the working diagnosis and subsequent therapy. However, samples should be examined with caution because results correlate poorly with prognosis. In view of the presence of coagulopathy, weigh the risk of liver biopsy against its contribution to diagnosis and management.
Two types of histology have been recognized in patients with FHF. The first type is usually observed in cases that stem from drug reactions or viral hepatitis. This type is characterized by extensive necrosis of the peripheral hepatocytes, with little or no regeneration. Hepatocyte necrosis with microvascular fat accumulation may be observed, especially in patients with FHF secondary to inborn errors of metabolism.
The second type of histology, observed in valproate toxicity, Reye syndrome, and other metabolic liver disease, is characterized by microvesicular steatosis and centrilobular necrosis.
Hackl C, Schlitt HJ, Melter M, Knoppke B, Loss M. Current developments in pediatric liver transplantation. World J Hepatol. 2015 Jun 18. 7 (11):1509-20. [Medline].
Kirnap M, Akdur A, Ozcay F, Soy E, Yildirim S, Moray G, et al. Liver Transplant for Fulminant Hepatic Failure: A Single-Center Experience. Exp Clin Transplant. 2015 May 30. [Medline].
Gotthardt D, Riediger C, Weiss KH, Encke J, Schemmer P, Schmidt J, et al. Fulminant hepatic failure: etiology and indications for liver transplantation. Nephrol Dial Transplant. 2007 Sep. 22 Suppl 8:viii5-viii8. [Medline].
Jain J, Jain M. Atypical manifestations of viral hepatitis A and E. Trop Doct. 2013 Jan. 43(1):17-8. [Medline].
Kumar KJ, Kumar HC, Manjunath VG, Anitha C, Mamatha S. Hepatitis A in children- clinical course, complications and laboratory profile. Indian J Pediatr. 2014 Jan. 81(1):15-9. [Medline].
El-Ashry R, Malek HA, Ghayaty EA, El-Gendy AA, Darwish A, Al-Tonbary Y. Treatment for hepatitis C virus-induced portal hypertension in leukemic children. Med Oncol. 2013. 30(2):559. [Medline].
Amin MD, Harpavat S, Leung DH. Drug-induced liver injury in children. Curr Opin Pediatr. 2015 Aug 13. [Medline].
Alonso EM, James LP, Zhang S, Squires RH, Pediatric Acute Liver Failure Study Group. Acetaminophen Adducts Detected in Serum of Pediatric Patients With Acute Liver Failure. J Pediatr Gastroenterol Nutr. 2015 Jul. 61 (1):102-7. [Medline].
Nazer H, Ede RJ, Mowat AP, Williams R. Wilson's disease in childhood. Variability of clinical presentation. Clin Pediatr (Phila). 1983 Nov. 22(11):755-7. [Medline].
Nazer H, Ede RJ, Mowat AP, Williams R. Wilson's disease: clinical presentation and use of prognostic index. Gut. 1986 Nov. 27(11):1377-81. [Medline].
Cochran JB, Losek JD. Acute liver failure in children. Pediatr Emerg Care. 2007 Feb. 23(2):129-35. [Medline].
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 May. 40(5):575-81. [Medline].
El-Karaksy HM, El-Shabrawi MM, Mohsen NA, El-Koofy NM, El-Akel WA, Fahmy ME. Study of predictive value of pediatric risk of mortality (PRISM) score in children with end stage liver disease and fulminant hepatic failure. Indian J Pediatr. 2011 Mar. 78(3):301-6. [Medline].
Sanchez MC, D'Agostino DE. Pediatric end-stage liver disease score in acute liver failure to assess poor prognosis. J Pediatr Gastroenterol Nutr. 2012 Feb. 54(2):193-6. [Medline].
Wlodzimirow KA, Eslami S, Abu-Hanna A, Nieuwoudt M, Chamuleau RA. A systematic review on prognostic indicators of acute on chronic liver failure and their predictive value for mortality. Liver Int. 2013 Jan. 33(1):40-52. [Medline].
Baker A, Alonso ME, Aw MM, et al. Hepatic failure and liver transplant: Working Group report of the second World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2004 Jun. 39 Suppl 2:S632-9. [Medline].
Dhawan A, Cheeseman P, Mieli-Vergani G. Approaches to acute liver failure in children. Pediatr Transplant. 2004 Dec. 8(6):584-8. [Medline].
Latif N, Mehmood K. Risk factors for fulminant hepatic failure and their relation with outcome in children. J Pak Med Assoc. 2010 Mar. 60(3):175-8. [Medline].
Alpert O, Sharma V, Cama S, Spencer S, Huang H. Liver transplant and quality of life in the pediatric population: a review update (2013-2014). Curr Opin Organ Transplant. 2015 Apr. 20 (2):216-21. [Medline].
Goss JA, Shackleton CR, Maggard M, et al. Liver transplantation for fulminant hepatic failure in the pediatric patient. Arch Surg. 1998 Aug. 133(8):839-46. [Medline].
Nakazawa A, Nakano N, Fukuda A, Sakamoto S, Imadome K, Kudo T, et al. Use of serial assessment of disease severity and liver biopsy for indication for liver transplantation in pediatric Epstein-Barr virus-induced fulminant hepatic failure. Liver Transpl. 2015 Mar. 21 (3):362-8. [Medline].
Baccarani U, Adani GL, Sainz M, et al. Human hepatocyte transplantation for acute liver failure: state of the art and analysis of cell sources. Transplant Proc. 2005 Jul-Aug. 37(6):2702-4. [Medline].
Lee HS, Choi GH, Joo DJ, Kim MS, Kim SI, Han KH, et al. Prognostic value of model for end-stage liver disease scores in patients with fulminant hepatic failure. Transplant Proc. 2013 Oct. 45(8):2992-4. [Medline].
Faraj W, Dar F, Bartlett A, Melendez HV, Marangoni G, Mukherji D, et al. Auxiliary liver transplantation for acute liver failure in children. Ann Surg. 2010 Feb. 251(2):351-6. [Medline].
Hattori H, Higuchi Y, Tsuji M, et al. Living-related liver transplantation and neurological outcome in children with fulminant hepatic failure. Transplantation. 1998 Mar 15. 65(5):686-92. [Medline].
Squires RH, Dhawan A, Alonso E, Narkewicz MR, Shneider BL, Rodriguez-Baez N, et al. Intravenous N-acetylcysteine in pediatric patients with non-acetaminophen acute liver failure: A placebo-controlled clinical trial. Hepatology. 2012 Aug 10. [Medline].