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

Background/Aim: Alpha-1-antitrypsin deficiency (alpha(1)ATD) is the commone st metabolic disease leading to liver transplantation (LT) in children. App roximately 10-15% of the PiZZ population develops liver disease. Five perce nt of them will require LT within the first 4 years of life. This study aim ed to investigate the prognosis of the liver disease associated with PiZZ a lpha(1)ATD in the era of liver transplantation and to determine predictors of outcome. Methods: We reviewed retrospectively the clinical notes of 97 consecutive p atients referred from January 1989, when LT became routinely available in o ur 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 pa tients 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 neonata l hepatitis at a median age of 1.6 months. Among infants with neonatal hepa titis who required LT, 18 out of 21 (86%) had jaundice for more than 6 week s compared with 34 of 61 (56%) who survived without LT (p<0.01), Children r equiring LT had higher aspartate aminotransferase (AST) at presentation (p< 0.0001) and both higher AST and gamma-glutamyl transferase (GGT) at 6 month s (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-s tage 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 child ren (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 alpha(1)ATD. Duration of jaundice, severity of histological features and biochemical abnormalitie s predict outcome at an early stage of the disease.