Most Alagille syndrome patients don’t reach adulthood with native liver
The burden of liver disease with early profound cholestasis in patients with Alagille syndrome (ALGS) had been previously underrecognized, according to results from the largest multicenter natural history study of cholestasis in ALGS.
In this study, 293 patients with ALGS with native liver were included. Out of 206 patients, 91% had JAGGED1 mutations and 4% had NOTCH2 mutations. At all ages, the mean height and weight z-scores were <-1.0. For every 10 mg/dL increase in total bilirubin, there was a decrease in height z-score by 0.10 (P = 0.03) and weight z-score by 0.15 (P = 0.007). Patients less than 1-year-old had a higher total bilirubin (median 6.9 mg/dL) compared to patients older than 13 years (1.3 mg/dL) Overall, 40% of participants had developed definite portal hypertension by the age of 20 years, and only 24% were estimated to be liver transplant-free by the age of 18.5 years. Reference Kamath BM, Ye W, Goodrich NP, et al. Outcomes of childhood cholestasis in Alagille syndrome: Results of a multicenter observational study. Hepatol Commun. 2020;4(3):387-398.doi: 10.1002/hep4.1468. PMID: 33313463; PMCID: PMC7049675.