End-stage chronic liver diseases (ESLD) form the major group (approx 80%) of indications for OLT in children, with biliary atresia as the commonest etiology (approx 50%). Acute and subacute causes of fulminant hepatic failure (FHF), metabolic liver diseases with debilitating extrahepatic manifestations, and primary liver tumors comprise the remainder. The median age of liver transplantation in children 0-18 years is about 18 months , reflecting the stage of progression to end-stage of the most frequent indication – end-stage biliary atresia and failed portoenterostomy.
Causes of these conditions are listed below:
- Chronic end-stage liver disease: biliary cirrhosis due to extrahepatic biliary atresia, Alagille’s syndrome, progressive familial intrahepatic cholestasis (PFIC) syndromes, sclerosing cholangitis, some cases of congenital hepatic fibrosis with Caroli’s disease, and Cystic Fibrosis liver disease (the latter may be in conjunction with lung transplantation; chronic hepatocellular disease due to neonatal hepatitis, chronic hepatitis B, C, autoimmune chronic active hepatitis, metabolic diseases such as alpha-1-antitrypsin deficiency, tyrosinaemia, Wilson’s disease, and cryptogenic cirrhosis; and vascular abnormalities such as Budd-Chiari syndrome
- Acute Fulminant liver failure: fulminant viral hepatitis (hepatitis A, B, C, adenovirus, CMV, measles, herpes, varicella, echovirus,), drug toxicity (acetaminophen, sodium valproate, halothane etc), toxin induced (amanita phylloides mushrooms), metabolic diseases (Wilson’s disease, galactosaemia, tyrosinaemia, fatty acid oxidation defects such as LCAD, LCHAD, neonatal haemochromatosis), and acute vascular diseases (veno-occlusive disease and Budd-Chiari syndrome)
- Hepatic Metabolic/genetic diseases with debilitating extrahepatic manifestations: glycogen storage disease type IV, III, Crigler-Najjar syndrome, urea cycle defects, protein C deficiency, familial hypercholesterolaemia, primary hyperoxaluria.
- Malignant liver neoplasms: hepatoblastoma, hepatocellular carcinoma, haemangioendothelioma
Criteria for Referral
Chronic End-Stage Liver Disease
There are multiple parameters used to predict the need for liver transplantation, and some scoring systems are available. The presence of synthetic failure, one or more complications, and features of progressive morbidity all indicate the need for OLT, considering also the potential waiting time for a suitable donor.
Note: Prior to availability of OLT, in biliary atresia and failed portoenterostomy (i.e., persisting jaundice), the median age of death was 14 months.
Complications include: Recurrent variceal bleeding, refractory ascites, recurrent spontaneous bacterial peritonitis, growth failure, intractable pruritus, rickets, pathological fractures, oxygen desaturation, intrapulmonary shunts, poor quality of life.
Parameters of synthetic failure include: PTT > 20 secs, albumin < 3.0, and indirect bilirubin > 100mg/dL, Na < 132, cholesterol < 100mg/dL
Acute Fulminant Liver Failure
Each case is assessed on an individual basis. However, without transplantation < 50% will recover. Thus patients should be referred to a transplant center, supported aggressively, and listed for transplant. Children with AFLF have the highest priority for regional sharing of donor organs. The option of live-related organ donation can be explored. When a donor becomes available, the decision for OLT can be made, but if while waiting, there are signs of stabilization (lack of progressive deterioration) or evidence of recovering function (improved coagulation parameters), transplantation may be avoided. However, urgent transplantation is considered: if INR is greater or equal to 4.0 (or P.T.>90s) plus three of the following:
- age <10 years
- non A non B or drug hepatitis
- period of encephalopathy with jaundice interval > 7 days
- serum bilirubin > 300umol/L
- liver biopsy shows < 50% viable hepatocytes and no regeneration
For acetaminiphen intoxication, consider transplant if pH < 7.3, creatinine > 0.3mmol/L and/or INR > 6.5.
Patients with proven mitochondrial defects, sometimes uncovered by Valproate have a poor neurological outcome and should not be transplanted. Urgent exclusion of these conditions may be warranted, and ‘antioxidant liver rescue’ therapy attempted. Genetic advice is mandatory.
primary extrahepatic unresectable/untreatable malignancy, malignancy metastatic to the liver, progressive terminal nonhepatic disease, uncontrolled systemic sepsis irreversible neurologic injury, mitochondrial disorders with progressive neurological involvement
Intrapulmonary shunts where PAO2 < 50 mm Hg, advanced or partially treated systemic infection, severe developmental or psychosocial problems obviating compliance and follow-up