ACUTE LIVER FAILURE

B. Rodeck

Kinderklinik, Medizinische Hochschule Hannover, Hannover, Germany

Acute liver failure is a rare disorder in childhood. The incidence in Germany is about 1:400,000 in children and adolescents up to 16 years of age. In general, fulminant liver failure is present when hepatic encephalopathy develops within 8 weeks of the first symptoms of illness without any previous history of underlying liver disease. Concerning children, in this definition severe impairment of liver function (prothrombin time < 40%; cholinesterase activity < 2,5 kU/l) should replace encephalopathy, since this is not obligatory in this age group. The aetiology of acute liver failure depends on age and geographic location. Overall, virus induced hepatitis is the most common cause of acute liver failure. In the neonatal age group metabolic diseases are more common. Later in infancy and childhood drug and toxins are more predominant. Other causes are autoimmune diseases, ischemia/abnormal perfusion and malignancy/infiltrative hepatopathies, infrequently heat stroke or malignant hyperthermia. Of course, in regions of endemic hepatitis B, this disorder accounts for a great part of acute liver failure. The first step in the pathophysiological cascade is the exposure of a susceptible child to an agent causing hepatocyte injury. The susceptibility to hepatic injury is determined by various factors, i.e. age, immunity, biochemical polymorphism or induction of drug- metabolizing enzymes. In principal, the acutely failing liver possesses the potential to regenerate. This spontaneous prognosis depends on the individual interaction between agent and host. The histopathological picture of acute liver failure is characterized by necrosis and loss of hepatocytes in most cases.

After a short history in most cases deep jaundice develops as well as elevated transaminases, signs of deteriorating liver function (deficiencies of clotting factors, reduced cholinesterase, increasing ammonia) and later on encephalopathy. Major complications are hypoglycemia, cerebral oedema, renal failure, acid/based and fluid/electrolyte disturbances, bleeding diathesis, hypoxia, circulatory problems, bacterial and fungal infections, bone marrow depression and pancreatitis. Development of multiorgan failure is possible. The main cause of death is cerebral oedema. The principles of conservative treatment are correction of metabolic disturbances, prevention of hepatic encephalopathy (protein restricted diet, enriched with branched chained aminoacids, selective gut sterilization) and intensive care management. In some aetiologies a specific therapy is available (virusstatic treatment in hepatitis, detoxification in Amanita phalloides or paracetamol poisoning, specific treatment in some metabolic disorders). In all but the mildest cases an early referal to a liver transplant unit is advisable in order to optimize the management and timing of transplantation. Several scores have been developed to standardize the indication of transplantation, however these are not validated in children. Organ replacement can be performed as whole-liver-, reduced-sized-liver-, living donor- and auxiliary transplantation. Systems for artificial liver support are still under investigation and not available for clinical practice yet. With optimal intensive care management and transplantation the survival rate of children with acute liver failure nowadays lies between 70-90%.