Retrospective analysis of 326 infants with infantile cholestasis reveals etiological spectrum

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Frontiers in Medicine Published April 22, 2026 Medically reviewed May 25, 2026 DOI ↗ By Dr. Sofia Müller, MD · Lifespan & Whole-Person Care

Key Takeaway

Note the etiological spectrum and biochemical markers in this retrospective cohort of 326 infants.

This retrospective cohort study at the Children's Hospital Affiliated to Shandong University involved 326 infants diagnosed with infantile cholestasis. The study aimed to characterize the etiological spectrum and clinical characteristics. No specific intervention or comparator was reported.

Clinical presentation included hepatomegaly in 62.9% of patients and light- or clay-colored stools in 56.7%. Biliary tract anomalies were present in 50.6% of the infants. Comorbidities were identified in 8.3% of the population. Etiology included biliary atresia in 161 cases, genetic metabolic liver diseases in 9.8% (32 patients), infectious causes in 7.4%, drug-related causes in 3.4%, idiopathic cholestasis in 6.7%, other rare causes in 0.9%, and undetermined etiology in 21.2%.

Comparative analysis between the biliary atresia subgroup and the genetic metabolic subgroup revealed no significant differences in sex or age distribution (P > 0.05). Genetic sequencing identified pathogenic or likely pathogenic variants in 60.0% of tested infants, with 33 variants identified in 55 tested infants. Biochemical markers differed significantly between subgroups. MMP-7 levels, direct bilirubin levels, and GGT levels were significantly higher in the biliary atresia subgroup compared to the genetic metabolic subgroup. GGT levels showed statistical significance with a P value of 0.002.

Safety data, including adverse events and discontinuations, were not reported. The study did not report practice relevance or funding sources. As an observational study, findings describe associations rather than causal relationships. Clinicians should interpret these etiological distributions within the context of the single-center design and lack of follow-up duration.

Study Details

Study typeCohort

EvidenceLevel 3

PublishedApr 2026

View Original Abstract ↓

ObjectiveTo retrospectively investigate the clinical characteristics and etiological spectrum of infantile cholestasis, with an emphasis on evolving diagnostic approaches.MethodsClinical data of 326 infants diagnosed with infantile cholestasis at the Children's Hospital Affiliated to Shandong University from January 2020 to December 2025 were retrospectively analyzed. Etiological distribution was systematically examined. Serum bile acid profiling was performed for suspected bile acid synthesis defects, and genetic sequencing for unexplained or suspected genetic cholestasis.ResultsAmong 326 infants with infantile cholestasis, 56.7% presented with light- or clay-colored stools, 62.9% had hepatomegaly, and 8.3% had comorbidities. The etiological spectrum included biliary tract anomalies [50.6%, including 161 biliary atresia (BA)], genetic metabolic liver diseases (9.8%, n = 32), infectious causes (7.4%), drug-related causes (3.4%), idiopathic cholestasis (6.7%), other rare causes (0.9%), and undetermined etiology (21.2%). No significant differences in sex or age were observed between the genetic metabolic group (n = 32) and BA group (n = 161) (both P > 0.05). After excluding 165 surgical cases, genetic testing was performed in 55 of 161 remaining infants (34.2%), with pathogenic or likely pathogenic variants identified in 33 (60.0% detection rate) across 14 genes (e.g., JAG1, SLC25A13, ABCC2). In an exploratory subgroup analysis (genetic metabolic, n = 16; BA, n = 20), the BA subgroup showed significantly higher levels of matrix metalloproteinase-7 (MMP-7), direct bilirubin, and GGT (P = 0.002 for GGT), with no other significant differences between the two subgroups.ConclusionThe etiology of infantile cholestasis is complex and highly heterogeneous. Genetic testing improves the diagnostic yield of inherited metabolic liver diseases. Serum bile acid profiling provides metabolomic signatures for etiological differentiation. Conventional liver function tests combined with serum MMP-7 represent a simple, reliable, noninvasive approach for early differentiation of biliary atresia.