The frequency of idiopathic cholestasis (IC) and of death or liver transplant appears to be declining among infants, with overall outcomes being favorable, according to a study published in the Journal of Pediatric Gastroenterology and Nutrition.

Cholestasis in neonates and young infants is commonly idiopathic. Prior studies, which were mostly small, retrospective, and single-center, suggest that IC is often self-limiting. Researchers sought to determine the frequency and natural history of infantile IC in a large, prospective, multicenter cohort.

Ninety-four infants with cholestasis were enrolled until up to 6 months of age in the Childhood Liver Disease Research Network (ChiLDReN ) Prospective Database of Infants with Cholestasis (PROBE) trial (ClinicalTrials.gov Identifier: NCT00061828).  Infants included in the study had a final diagnosis of IC and were followed until up to 30 months of age.


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The researchers found that male sex, preterm birth, and low birth weight were frequent, with no significant differences among outcomes. Clinical outcomes included death (n=1), liver transplant (n=1), biochemical resolution (total bilirubin [TB] >1 mg/dL and alanine transaminase [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 appeared to occur at a median of 9 months of age. Gamma-glutamyl transferase (GGT) was <100 U/L at baseline in 34 of 83 participants (41%), suggesting a role for variants in genes associated with low-GGT cholestasis in some cases of IC.

Investigators acknowledge their study may underrepresent perinatal hypoxemia/asphyxia or arrhythmia as a susceptibility factor for IC, as they lacked detailed patient data on this topic. Further studies with larger patient cohorts are needed.

The authors concluded, “Frequency of IC and of death or liver transplant was less common in this cohort than in previously published cohorts, likely because of recent discovery and diagnosis of genetic etiologies of severe/persistent cholestasis that previously were labeled as idiopathic.” They added, “Low/normal GGT was common, possibly indicating a role for variants in genes associated with low-GGT cholestasis—this warrants further study.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Hertel PM, Hawthorne K, Kim S, et al, for the Childhood Liver Disease Research Network (ChiLDReN). Presentation and outcomes of infants with idiopathic cholestasis: a multicenter prospective study. JPGN. 2021;73(4):478-484. doi: 10.1097/MPG.0000000000003248