Prognosis of alpha-1-antitrypsin deficiency-related liver disease in the era of paediatric liver transplantion

Background/Aim: Alpha-1-antitrypsin deficiency (α1ATD) is the commonest metabolic disease leading to liver transplantation (LT) in children. Approximately 10–15% of the PiZZ population develops liver disease. Five percent of them will require LT within the first 4 years of life. This study aimed to investigate the prognosis of the liver disease associated with PiZZ α1ATD in the era of liver transplantation and to determine predictors of outcome. Methods: We reviewed retrospectively the clinical notes of 97 consecutive patients referred from January 1989, when LT became routinely available in our Unit, to July 1998. Results: Of 26 (27%) patients who developed endstage liver disease, 24 have been transplanted and two are waiting for LT. Twenty-one (81%) of these patients presented with neonatal hepatitis at a median age of 2.1 months. Of 71 (73%) children who have not required LT, 61 (86%) presented with neonatal hepatitis at a median age of 1.6 months. Among infants with neonatal hepatitis who required LT, 18 out of 21 (86%) had jaundice for more than 6 weeks compared with 34 of 61 (56%) who survived without LT (p<0.01). Children requiring LT had higher aspartate aminotransferase (AST) at presentation (p<0.0001) and both higher AST and gamma-glutamyl transferase (GGT) at 6 months (p<0.001), 1-year (p<0.0003) and 5-year (p 0.01) follow up when compared to those who are well without LT. Furthermore, children who developed end-stage liver disease more frequently had severe bile duct reduplication (p<0.01), severe fibrosis (p<0.03) with bridging septa (p<0.02) and established cirrhosis (p<0.04) in the initial liver biopsy. Ninety-five of the 97 children (98%) are currently alive; two died after LT. Conclusions: The advent of liver transplantation has significantly improved the prognosis of liver disease associated with PiZZ α1ATD. Duration of jaundice, severity of histological features and biochemical abnormalities predict outcome at an early stage of the disease.