Managing Liver Failure D a Kelly

Managing Liver Failure D a Kelly

660 Postgrad Med J: first published as 10.1136/pmj.78.925.660 on 1 November 2002. Downloaded from BEST PRACTICE Managing liver failure D A Kelly ............................................................................................................................. Postgrad Med J 2002;78:660–667 Liver disease is rare in childhood, but important new Clinical presentation developments have altered the natural history and The clinical presentation depends on the aeti- ology of acute liver failure but the presentation outcome. It is important that clinicians are aware of may either be acute, within days, or prolonged to these diseases and their management. Acute liver failure 10 weeks if due to metabolic liver disease. The is most often due to viral hepatitis, paracetamol extent of jaundice and encephalopathy is variable in the early stages, but all children have coagu- overdose, or inherited metabolic liver disease. The lopathy. Encephalopathy is particularly difficult to clinical presentation includes jaundice, coagulopathy, diagnose in neonates. Vomiting and poor feeding and encephalopathy. Early diagnosis is necessary to are early signs, while irritability and reversal of day/night sleep patterns indicates more estab- prevent complications such as cerebral oedema, lished hepatic encephalopathy. In older children gastrointestinal bleeding, and renal failure. Early encephalopathy may present with aggressive supportive management, in particular intravenous behaviour or convulsions. N-acetylcysteine, may be effective but liver Neonatal acute liver failure transplantation is usually the definitive treatment and The commonest cause of acute liver failure in thus early referral to a specialist unit for liver neonates is septicaemia secondary to Escherichia coli, Staphylococcus aureus, or herpes simplex (box 1 transplantation is mandatory. Chronic liver failure may and table 1). Other causes include adenovirus, be due to unresolved neonatal liver disease, either echovirus, and Coxsackie virus. Acute liver failure secondary to hepatitis B usually presents at about inherited biliary hypoplasia or extrahepatic biliary 12 weeks of age while hepatitis A is rare in atresia, while in older children, autoimmune liver neonates. Hepatitis C does not cause acute liver disease or cystic fibrosis are the commonest causes. failure in neonates. Treatment includes specific medication, nutritional Hepatitis B support, and liver transplantation, which now has a Hepatitis B is vertically transmitted during pregnancy or delivery. The transmission rate is 90% survival with good quality life. http://pmj.bmj.com/ approximately 70% in mothers who are hepatitis .......................................................................... B surface antigen and hepatitis B e antigen posi- tive. Most infected infants will become asympto- ACUTE LIVER FAILURE matic carriers. In contrast, infants born to moth- Acute liver failure or fulminant hepatitis is rare ers who are hepatitis B e antigen negative have a in childhood, but has a mortality of 70% without high risk of developing fulminant hepatitis appropriate management and/or liver transplan- within the first 12 weeks of life due the transmis- sion of a pre-core mutant hepatitis virus from tation. Fulminant hepatic failure is defined as on September 28, 2021 by guest. Protected copyright. the development of hepatic necrosis with mother to child.23 Both the development of the encephalopathy within eight weeks of the onset carrier state and fulminant hepatitis B may be of liver disease. This definition is not useful for prevented by vaccination of all infants of hepati- paediatric acute liver failure as the clinical tis B carrier mothers, irrespective of their e presentation may be prolonged particularly if antigen status. secondary to autoimmune or metabolic liver disease.1 Neonatal haemochromatosis The acute liver damage may be secondary to a Neonatal haemochromatosis is a rare disorder, virus, drug, or toxin or immune mediated attack. which is associated with iron accumulation in The underlying mechanism is unknown but is liver, pancreas, heart, and brain. It is not known multifactorial and depends on the age, sus- whether the disease is inherited with autosomal ....................... ceptibility of the patient, and the extent of recessive inheritance or is an acquired defect of hepatic injury. The main pathological features iron handling in pregnancy. Clinical presentation Correspondence to: may be within hours or weeks of birth with jaun- include severe hepatic necrosis, loss of hepatic Professor Deirdre A Kelly, dice, hypoglycaemia, and severe coagulopathy. architecture, and absence of hepatic regenera- Liver Unit, Birmingham Encephalopathy, although present may not be Children’s Hospital NHS tion. Trust, Steelhouse Lane, The aetiology of acute liver failure varies Birmingham B4 6NH, UK; Deirdre.Kelly@ depending on the age of the child (box 1). In ................................................. bhamchildrens.wmids.nhs.uk neonates, inherited metabolic liver disease or Abbreviations: FIC, familial intrahepatic cholestasis; infection is likely while viral hepatitis, auto- Submitted 27 May 2002 NTBC, 2 (2 nitro-4-trifluoromethylbenzoyl)-1, Accepted 19 June 2002 immune liver disease, or drug induced liver 3-cyclohexenedione; TIPSS, transjugular intrahepatic ....................... failure are common in older children. portosystemic stent shunt www.postgradmedj.com Managing liver failure 661 Postgrad Med J: first published as 10.1136/pmj.78.925.660 on 1 November 2002. Downloaded from Box 1: Aetiology of acute liver failure Box 2: Supportive management of fulminant hepatitis Neonate/infant up to 6 months • No sedation except for procedures. • Infection: septicaemia, hepatitis B, adenovirus, echovirus, • Monitor: neurological observations 4–6 hourly, gastric pH Coxsackie B. (>5), blood glucose (>4 mmol/l), acid-base/electrolytes, • Metabolic: neonatal haemochromatosis, tyrosinaemia type prothrombin time, partial thromboplastin time. I, mitochondrial disorders, fatty acid oxidation defects. • Fluid balance: 75% maintenance. • Poisoning: paracetamol. Maintain circulating volume with colloid/fresh frozen • Familial haemophagocytic syndrome. plasma. Consider: frusemide infusion, haemofiltration. Children >6 months • Coagulation support (fresh frozen plasma, cryoprecipitate). • Viral hepatitis: hepatitis A/B/E/non-A-G, Epstein-Barr • Drugs: vitamin K (2–10 mg), ranitidine (3 mg/kg), virus, parvovirus B19. sucralfate (2–4 g/day), lactulose (5–20 ml/day), • Autoimmune type I or II. N-acetylcysteine (70 mg/kg/6 hour), +/- broad spectrum • Drug induced: paracetamol overdose, sodium valproate, antibiotics, fluconazole. carbamazepine, isoniazid, halothane. • Nutrition: enteral feeding (1–2 g protein/day), parenteral • Metabolic: Wilson’s disease, Alpers disease. nutrition if ventilated. obvious. The diagnosis is suggested by raised ferritin levels coagulopathy, encephalopathy, ascites, and occasionally hyper- (2000–3000 µg/l) and confirmed by demonstrating a high insulinism. The diagnosis is based on increased plasma serum iron with hypersaturation of iron binding capacity tyrosine, phenylalanine, methionine and confirmed by identi- (95%–105%) and the demonstration of extrahepatic haemosi- fying a toxic metabolite, succinylacetone in the urine, or by derosis. Because of the severe coagulopathy liver biopsy is enzyme analysis of skin fibroblasts. Management includes usually contraindicated but extrahepatic siderosis may be supportive management of acute liver failure (box 2) and with demonstrated in salivary glands obtained by lip biopsy or the 2 (2 nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexenedione 5 demonstration of iron accumulation in pancreas and brain on (NTBC), which prevents the formation of toxic metabolites magnetic resonance imaging. Intensive supportive manage- and allows hepatic regeneration. Children who fail to respond 6 ment of the liver failure and an antioxidant cocktail (boxes 2 to NTBC should be offered liver transplantation. and 3) may be effective if begun within 24–48 hours of birth in milder cases but liver transplantation is usually required.4 Mitochondrial disorders Mitochondrial disorders present with acute liver failure in the Tyrosinaemia type I context of multiorgan disease. There are many different clini- Tyrosinaemia type I is an autosomal recessive disorder cal phenotypes and modes of inheritance including transmis- secondary to deficiency of fumaryl acetoacetase which sion through maternal DNA. The disorders include deficien- prevents the metabolism of tyrosine leading to the accumula- cies of the electron transport chain enzymes or depletion of tion of toxic metabolites, which damage liver, kidneys, heart, mitochondrial DNA. Neonates and infants present with jaun- and brain. Infants present between 1 and 6 months of age dice, coagulopathy, and neurological features very similar to with acute liver failure with mild jaundice, hypoglycaemia, hepatic encephalopathy and multiorgan failure (cardiac, renal, bone marrow). Infants have metabolic acidosis with a raised blood lactate. Other useful investigations are an http://pmj.bmj.com/ Table 1 Investigations for acute and chronic liver increased plasma 3-hydroxybutyrate-acetoacetate ratio (>2) failure in children or detection of abnormal organic acids such as urinary 3-methylglutaconic acid. Evidence of multiorgan involvement Investigations is confirmed by muscle biopsy which may demonstrate abnor- Infection mal mitochondria while an increased

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