Clinicopathologic Characterization of Liver Biopsies of Patients with Congenital Hyperinsulinism Presenting with Neonatal Cholestasis

Abstract

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.