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Multicenter Study
. 2021 Oct 1;73(4):478-484.
doi: 10.1097/MPG.0000000000003248.

Presentation and Outcomes of Infants With Idiopathic Cholestasis: A Multicenter Prospective Study

Paula M Hertel  1 , Kieran Hawthorne  2 , Sehee Kim  3 , Milton J Finegold  1 , Benjamin L Shneider  1 , James E Squires  4 , Nitika A Gupta  5 , Laura N Bull  6 , Karen F Murray  7 , Nanda Kerkar  8   9 , Vicky L Ng  10 , Jean P Molleston  11 , Jorge A Bezerra  12 , Kathleen M Loomes  13   14 , Sarah A Taylor  15 , Kathleen B Schwarz  16 , Yumirle P Turmelle  17 , Philip Rosenthal  18 , John C Magee  19 , Ronald J Sokol  20 ; Childhood Liver Disease Research Network (ChiLDReN)
Affiliations
Multicenter Study

Presentation and Outcomes of Infants With Idiopathic Cholestasis: A Multicenter Prospective Study

Paula M Hertel et al. J Pediatr Gastroenterol Nutr. .

Abstract

Objectives: The aim of the study was to determine the frequency and natural history of infantile idiopathic cholestasis (IC) in a large, prospective, multicenter 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 of 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 because of 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.

Trial registration: ClinicalTrials.gov NCT00061828.

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Figures

FIGURE 1
FIGURE 1
LOESS curve for alanine aminotransferase by resolution status. Serum ALT of participants during the study period is shown. y-axis represents serum ALT (U/L) and x-axis shows the age of the patients (in months) at the time of the lab draw. Shaded areas represent 95% confidence intervals. Patients with biochemical resolution (circle) are compared with patients who did not have resolution (cross). ALT = alanine aminotransferase, LOESS = LOcally Estimated Scatterplot Smoothing.
FIGURE 2
FIGURE 2
LOESS curve for total bilirubin by resolution status. The total bilirubin of participants during the enrollment period is shown. y-axis represents total bilirubin (mg/dL) and x-axis shows the age of the patients (in months) at the time of the lab draw. Shaded areas represent 95% confidence intervals. Patients with biochemical resolution (circle) are compared with patients who did not have resolution (cross).
FIGURE 3
FIGURE 3
LOESS curve for gamma-glutamyl transferase by resolution status. Serum GGT of patients during the enrollment period is shown. y-axis represents serum GGT (U/L) and x-axis shows the age of the patients (in months) at the time of the lab draw. Shaded areas represent 95% confidence intervals. Patients with biochemical resolution (circle) are compared with patients who did not have biochemical resolution (cross). GGT = gamma-glutamyl transferase.
See this image and copyright information in PMC

References

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