The Brazilian Alagille syndrome study: New insights from a multicenter national cohort
Elisa Carvalho, Gilda Porta, Irene Kazue Miura, Cristina Helena Targa Ferreira, Luciana Rodrigues Silva, Natascha Silva Sandy, Eleonora Druve Tavares Fagundes, Eliene Oliveira, Aline Falleiros Freitas, Adriana Maria Alves de Tommaso, Regina Sawamura, Melina Utz Melere, Sandra Maria Goncalves Vieira, Renata Belém Pessoa de Melo Seixas, Isadora de Carvalho Trevizoli, Alexandre Rodrigues Ferreira, Adriana Porta Miche Hirschfeld, Renata Pereira Sustovich Pugliese, Cibele Dantas Ferreira Marques, Maria Angela Bellomo Brandão, Raquel Borges Pinto, Leticia Helena Caldas Lopes, Jussara Melo de Cerqueira Maia, Ana Cristina Vieira de Melo, Carolina Sores Silva, Luiza Salgado Nader, Maria Tereza Guiotti, Roberta Vacari Alcântara, Leonardo Resende, Bruno Pereira Ribeiro Rocha, Nilza Maria Medeiros Perin, Adriana Teixeira Rodrigues, Vera Lúcia Baggio Danesi, Gabriel Hessel, Themis Reverbel SilveiraAbstract
Objectives
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).
Methods
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.
Results
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.
Conclusions
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.