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Updated: Jan 10, 2026
Isolation of Neonatal Extrahepatic Cholangiocytes
Published on: June 5, 2014
Clinicopathologic Characterization of Liver Biopsies of Patients with Congenital Hyperinsulinism Presenting with
Iván A González1, Winnie Sigal2,3, Alyssa Baccarella4
1Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Insights
Congenital hyperinsulinism (HI) in infants can cause conjugated hyperbilirubinemia, mimicking biliary atresia. Liver biopsies reveal giant cell hepatitis, not obstructive biliary disease, in these HI patients.
Area of Science:
- Pediatric Gastroenterology
- Hepatology
- Neonatology
Background:
- Congenital hyperinsulinism (HI) is a critical neonatal hypoglycemia condition.
- Some infants with HI develop conjugated hyperbilirubinemia, mimicking biliary atresia.
- Distinguishing HI-related cholestasis from other liver diseases is crucial for appropriate management.
Purpose of the Study:
- To characterize the liver biopsy findings in infants with congenital hyperinsulinism (HI) and cholestasis.
- To differentiate the histological features of HI-associated cholestasis from biliary atresia.
- To evaluate the clinical course and treatment response in these patients.
Main Methods:
- Retrospective analysis of liver biopsies from seven infants with congenital HI and cholestasis.
- Review of clinical data, laboratory results, and histological findings.
- Correlation of biopsy findings with clinical presentation and outcomes.
Main Results:
- All seven patients exhibited hepatocyte giant cell transformation and cholestasis.
- Periportal fibrosis and bile duct proliferation were observed in some cases, but ductular reaction was minimal.
- No evidence of bile plugs, portal edema, or generalized ductular reaction was found, differentiating from obstructive biliary disease.
- Five out of seven patients showed improvement or resolution of cholestasis after ursodiol treatment.
Conclusions:
- Liver biopsies in infants with congenital hyperinsulinism and cholestasis demonstrate a characteristic giant cell hepatitis pattern.
- These histological findings are distinct from those seen in biliary atresia or other obstructive biliary processes.
- Giant cell hepatitis in the context of HI and cholestasis can resolve with appropriate management.
Background:
Congenital hyperinsulinism (HI) is a severe form of hypoglycemia presenting in newborns and infants. Some affected patients develop conjugated hyperbilirubinemia potentially raising concern for biliary atresia.
Methods:
Retrospective study characterizing the liver biopsies of patients with congenital HI presenting with cholestasis.
Results:
Seven patients were identified with a median age of 2 months (range: 1-8) and a median gestational age of 36 weeks at birth (range: 28-38). Three patients had an underlying ABCC8 variant, and 2 patients had Beckwith-Wiedemann/11p Overgrowth syndrome. The median total bilirubin, conjugated bilirubin, and gamma-glutamyl transferase levels were 6.5 mg/dL (range: 1.1-18.1), 2.0 mg/dL (range: 0.0-10.7), and 176 Units/L (range: 60-395), respectively. Four patients were on total parental nutrition at the time of biopsy. All cases demonstrated hepatocyte giant cell transformation with cholestasis. Half of the cases showed periportal fibrosis and all had some degree of bile duct proliferation; however, ductular reaction was absent in most cases. None of the cases demonstrated portal stromal edema, bile plugs, or a generalized ductular reaction. All patients received ursodiol and at most recent follow up 5 patients had improvement in, or resolution of, the cholestasis.
Conclusions:
Liver biopsies from patients with HI and cholestasis show a giant cell hepatitis pattern without features of a biliary obstructive process.
