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This article is the author’s final published version in Liver international : official journal of the International Association for the Study of the Liver, Volume 42, Issue 7, July 2022, Pages 1593-1604.

The published version is available at Copyright © Aronson et al.


Background and Aims Crigler-Najjar syndrome (CNS) is a disorder of bilirubin conjugation leading to brain damage and death without treatment. Although cohort studies of limited size have been published, uncertainty about outcome, co-morbidities, occurence of liver fibrosis and treatment outcome remains. With this worldwide cohort study, we aim to add substantial knowledge to the previously published data.

Methods Anonymized retrospective data of CNS patients were collected in a web-based registry platform.

Results Clinical data of 221 CNS patients (46% female, severe phenotype n = 209) were collected. At the time of analysis, 59 CNS patients were deceased. Mean serum total bilirubin (TB) was 300 μmoL/L, mean conjugated bilirubin (CB) 14.4 μmoL/L. The incidence of neurologic symptoms was 10.7%. Elevated alanine aminotransferase (ALT, >70 U/L) was present in 43/221 (19.5%) and the mean gamma-glutamyl transpeptidase (GGT) was 54 U/L. CB and TB did not correlate with aspartate aminotransferase (AST), ALT or GGT. TB was higher in males than in females (316 vs. 287 μmol/L; p < .001). Cholelithiasis was detected in 14 of 91 ultrasound examinations. In 5 of 31 CNS patients with liver fibrosis evaluation advanced fibrosis and significant higher AST were detected. Liver transplantation (LT) was performed in 26 CNS patients at the median age of 9 years (0–32 years). A subgroup of 75 CNS patients showed high TB (444 ± 141 μmoL/L) and high mortality/morbidity because of inadequate access to treatment.

Conclusions This largest cohort of CNS patients to date shows the urgent need to globally expand access to therapy and gives insight into the clinical course and outcome of different treatment strategies. However, some questions need ongoing examination, especially regarding liver fibrosis and the timing of LT.

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This work is licensed under a Creative Commons Attribution 4.0 License.

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