Liver disease in infancy: a 20 year perspective.

In Northern Europe and North America the majority ofchildren with chronic or life threatening liver disease first develop features of liver disease in early infancy. They usually have a hepatitis syndrome characterised by conjugated hyperbilirubinaemia, abnormal biochemical tests of liver function, hepatomegaly with or without splenomegaly and partial or complete cholestasis. There may be features caused by malabsorption, particularly offat soluble vitamin K. It is from this cohort that the majority of children requiring transplantation are drawn. Such liver disease may occur in as many as 1 in 250 newborn infants.'2 During the development ofthe paediatric liver service at King's, in fruitful cooperation with the adult Liver Unit, we have identified important differences in some aspects of the clinical and pathobiological features of chronic liver disease which occur in children and adults, such as autoimmune chronic active hepatitis and primary sclerosing cholangitis.34 Our major efforts, however, have been to identify and improve the treatment of those with progressive liver disease starting in infancy. These account for over 50% of patients referred, the numbers in the main categories being given in the Table. This review provides an opportunity to consider some developments in which we have participated in the last 20 years. We highlight four advances which have had a major impact on the management of these disorders. Most important has been the observation that a large proportion of patients with biliary atresia could have prolonged survival with a good quality oflife after successful porto-enterostomy. The second has been identifying the role of alpha-l-antitrypsin deficiency (PIZZ) as a genetic factor associated with a particularly severe form of the syndrome frequently leading to cirrhosis. The third has been the developments in molecular biology which have led to the identification of rare genetic or congenital disorders presenting as neonatal hepatitis, gradually reducing the percentage of benign cryptogenic cases. Three will be considered: Niemann-Pick type 2, Zellweger's syndrome and Alagille's syndrome. Lastly, there has been the increased awareness of the importance of liver disease in children and the provision of improved treatment and research facilities which has come from the activities of the Children's Liver Disease Foundation.