https://pubmed.ncbi.nlm.nih.gov/34310436/ Cholestasis

J Pediatr Gastroenterol Nutr. 2021 Jul 23.
doi: 10.1097/MPG.0000000000003248.Online ahead of print.

Presentation and Outcomes of Infants with Idiopathic Cholestasis: A Multi-Center Prospective Study

Paula M Hertel 1, Kieran Hawthorne, Sehee Kim, Milton J Finegold, Benjamin L Shneider, James E Squires, Nitika A Gupta, Laura N Bull, Karen F Murray, Nanda Kerkar, Vicky L Ng, Jean P Molleston, Jorge A Bezerra, Kathleen M Loomes, Sarah A Taylor, Kathleen B Schwarz, Yumirle P Turmelle, Philip Rosenthal, John C Magee, Ronald J Sokol, Childhood Liver Disease Research Network (ChiLDReN)

Abstract
Objectives: To determine the frequency and natural history of infantile idiopathic cholestasis (IC) in a large, prospective, multi-center cohort of infants.

Methods: We studied 94 cholestatic infants enrolled up to 6 months of age in the NIDDK ChiLDReN (Childhood Liver Disease Research Network) "PROBE" protocol with a final diagnosis of IC; they were followed up to 30 months of age.

Results: Male sex (66/94; 70%), preterm birth (22/90 with data; 24% born at < 37 weeks' gestational age), and low birth weight (25/89; 28% born at <2500 g) were frequent, with no significant differences between outcomes. Clinical outcomes included death (n = 1), liver transplant (n = 1), biochemical resolution (total bilirubin [TB] ≤1 mg/dL and ALT < 35 U/L; n = 51), partial resolution (TB > 1 mg/dL and/or ALT > 35 U/L; n = 7), and exited healthy (resolved disease per study site report but without documented biochemical resolution; n = 34). Biochemical resolution occurred at median of 9 months of age. GGT was < 100 U/L at baseline in 34/83 participants (41%).

Conclusions: Frequency of IC and of death or liver transplant was less common in this cohort than in previously published cohorts, likely due to recent discovery and diagnosis of genetic etiologies of severe/persistent cholestasis that previously were labeled as idiopathic.Preterm birth and other factors associated with increased vulnerability in neonates are relatively frequent and may contribute to IC. Overall outcome in IC is excellent. Low/normal GGT was common, possibly indicating a role for variants in genes associated with low-GGT cholestasis - this warrants further study.