Natural History of Liver Disease in a Large International Cohort of Children with Alagille syndrome:Results from The GALA Study

BACKGROUND: Alagille syndrome (ALGS) is a multisystem disorder, characterized by cholestasis. Existing outcome data are largely derived from tertiary centers and real-world data are lacking. This study aimed to elucidate the natural history of liver disease in a contemporary, international, cohort of children with ALGS.METHODS: Multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born Jan-1997 - Aug-2019. Native liver survival (NLS) and event-free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS.RESULTS: 1433 children (57% male) from 67 centers in 29 countries were included. 10 and 18-years NLS rates were 54.4% and 40.3%. By 10 and 18-years, 51.5% and 66.0% of ALGS children experienced ≥1 adverse liver-related event (CEPH, transplant or death). Children (&gt;6 and ≤12 months) with median total bilirubin (TB) levels between ≥5.0 and &lt;10.0 mg/dL had a 4.1-fold (95% CI 1.6 - 10.8) and those ≥10.0 mg/dL had an 8.0-fold (95% CI 3.4 - 18.4) increased risk of developing CEPH compared with those &lt;5.0 mg/dL. Median TB levels between ≥5.0 and &lt;10.0 mg/dL and &gt;10.0 mg/dL were associated with a 4.8 (95% CI 2.4 - 9.7) and 15.6 (95% CI 8.7 - 28.2) increased risk of transplantation relative to &lt;5.0 mg/dL. Median TB &lt;5.0 mg/dL were associated with higher NLS rates relative to ≥5.0 mg/dL, with 79% reaching adulthood with native liver (p&lt;0.001).CONCLUSIONS: In this large international cohort of ALGS, only 40.3% of children reach adulthood with their native liver. A TB &lt;5.0 mg/dL between 6-and-12-months of age is associated with better hepatic outcomes. These thresholds provide clinicians with an objective tool to assist with clinical decision-making and in the evaluation of novel therapies.</p

Paediatric liver transplantation in Australia and New Zealand: 1985-2018

Liver transplantation has become the standard of care for children with end-stage liver disease. In Australia and New Zealand, there are four paediatric liver transplant units, in Sydney, Melbourne, Brisbane and Auckland. Over the past 30 years, there have been significant changes to indications for transplant, as well as medical and surgical advances. In this paper, using retrospective data from the Australia and New Zealand Liver Transplant Registry, we review 977 children (less than 16 years of age) who underwent liver transplant from 1985 to 2018. The most common indication was biliary atresia (54%), although there has been an increase in other indications, including inborn errors of metabolism, fulminant hepatic failure and malignant liver tumours. Over the past 3 decades, areas of change and innovation include: the use of 'split grafts' to enable an adult and a child to receive the same donor liver, live donation, improvements in immunosuppressive regimens and infectious prophylaxis protocols and innovative surgical techniques allowing transplantation in smaller infants. The outcomes for children who undergo liver transplant in ANZ are excellent, with current 10-year patient survival rates of 95%, comparable to other larger centres around the world