Cholestasis, Intrahepatic: Idiopathic hepatitis

Key Features

Essentials of Diagnosis

• Elevated total and conjugated bilirubin

• Hepatomegaly and dark urine

• Patency of extrahepatic biliary tree

General Considerations

• Accounts for 20–30% of cases of neonatal intrahepatic cholestasis

• However, it is decreasing in frequency as new causes of cholestasis are discovered

• Degree of cholestasis is variable

• May be indistinguishable from extrahepatic causes in 10% of cases

Clinical Findings

Symptoms and Signs

• Intrauterine growth retardation

• Prematurity

• Poor feeding and growth

• Emesis

• Partially or intermittently acholic stools

• Serious hemorrhage from vitamin K deficiency may also be present

• Neonatal lupus erythematosus may present with giant-cell hepatitis; however, thrombocytopenia, rash, or congenital heart block is usually also present

Differential Diagnosis

• Viral infections

• α₁-Antitrypsin deficiency

• Alagille syndrome

• Niemann-Pick type C disease (NPC)

• Progressive familial intrahepatic cholestasis (PFIC)

• Citrin deficiency

• Neonatal hemochromatosis

• Bile acid synthesis defects

Diagnosis

• HIDA scanning and ultrasonography may help verify patency of biliary tree if stools are acholic

• Liver biopsy findings

  • Usually diagnostic after age 6–8 weeks

  • May be misleading before age 6 weeks, since there is overlap with biliary atresia histology

• γ-Glutamyl transpeptidase (GGT) levels are normal or now in

  • Idiopathic neonatal hepatitis

  • Progressive familial intrahepatic cholestasis (PFIC) types I and II

  • Arthrogryposis–renal dysfunction–cholestasis syndrome (ARC) syndrome

  • Disease due to bile acid synthesis defects

• Indications for intraoperative cholangiography, endoscopic retrograde cholangiopancreatography (ERCP), or percutaneous cholecystography

  • Failure to detect patency of the biliary tree

  • Nondiagnostic liver biopsy findings

  • Persisting complete cholestasis (acholic stools)

Treatment

• Choleretics, a special formula with medium-chain triglycerides (eg, Pregestimil, Alimentum)

• Breast milk (if growth is adequate)

• Supplemental fat-soluble vitamins in water-soluble form

• Continue therapy as long as significant cholestasis remains (conjugated bilirubin > 1 mg/dL)

• Surgical reconstruction of hypoplastic biliary trees in Alagille syndrome should not be attempted

Outcome

Follow-Up

• Fat-soluble vitamin serum levels and INR should be monitored at regular intervals while supplements are given and repeated at least once after their discontinuation

Prognosis

• Around 80% patients recover without significant hepatic fibrosis

• However, failure to resolve the cholestatic picture by age 6–12 months is associated with progressive liver disease and evolving cirrhosis

• Liver transplantation has been successful when signs of hepatic decompensation are noted (rising bilirubin, coagulopathy, intractable ascites)

References