The Brazilian Alagille syndrome study: New insights from a multicenter national cohort

To elucidate the natural history of liver disease and identify the predictors of native liver survival (NLS) in a Brazilian cohort of children with Alagille syndrome (ALGS).

Multicenter retrospective cohort study of children with ALGS. Descriptive statistics summarized clinical data. Overall survival was estimated using Kaplan-Meier curves. NLS was analyzed with competing risk models. Associations between laboratory parameters and NLS were tested using Pearson's chi-square.

From 14 Brazilian reference centers, 120 children (52.5% male) were included, with mean age at diagnosis of 17.8 months and a median follow-up time of 88.5 months. Most presented characteristic facies (89.9%), jaundice (88.2%), pruritus (87.9%), and neonatal cholestasis (79.2%). Thirty percent underwent liver transplantation (LT) and 6.7% died. Jaundice, xanthomas, hepatomegaly, splenomegaly, and presence of excoriations were significantly associated with the need for LT or death. Direct bilirubin (DB) > 6 mg/dL, cholesterol >300 mg/dL, increased aspartate aminotransferase (AST) > 5 times the upper limit of normal (ULN), and AST-to-platelet ratio index (APRI) > 1 were associated with a significantly increased risk of LT or death, with hazard ratios of 18.2 (p < 0.001, 95% confidence interval [95% CI] = 5.1-64.5), 3.4 (p = 0.016, 95% CI = 1.3-9.2), 3.9 (p = 0.018, 95% CI = 1.2-12.4), and 10.2 (p = 0.013, 95% CI = 1.3-82.2), respectively.

The main clinical manifestations included characteristic facies, jaundice, and pruritus. Higher rates of LT or death were associated with jaundice, xanthomas, hepatomegaly, splenomegaly and presence of excoriations. Higher rates of NLS were associated with DB levels below 6 mg/dL, cholesterol levels below 300 mg/dL, AST levels <5x ULN, and an APRI < 1.