Autoimmune Sclerosing Cholangitis

Autoimmune sclerosing cholangitis is a childhood and adolescent disease with features of autoimmune hepatitis and of sclerosing cholangitis, with a better response of hepatitis than of the biliary disease.

It is as common as autoimmune hepatitis in children with a liver biopsy showing interface hepatitis, and about half have inflammatory bowel disease. Autoantibodies (antinuclear, smooth muscle and anti-neutrophil cytoplasmic) and high IgG are found.

Diagnosis rests on autoimmune hepatitis features plus abnormal cholangiography. Many cases are discovered in children being treated for autoimmune hepatitis.

Pathophysiology.

Autoimmune injury to both hepatocytes and bile ducts, with immune dysregulation and genetic susceptibility, produces interface hepatitis and periductal fibrosis.

Fatigue, abdominal pain, jaundice, pruritus, weight loss, fever, diarrhoea, hepatosplenomegaly and, in some, cholangitis.

Red flags.

• Acute liver failure presentation.
• Cholangitis.
• Portal hypertension with bleeding.

Liver tests (raised aminotransferases, with raised gamma glutamyl transferase), IgG, antinuclear, smooth muscle and anti-neutrophil cytoplasmic antibodies. Magnetic resonance cholangiopancreatography at diagnosis shows intrahepatic and extrahepatic duct changes. Liver biopsy shows interface hepatitis, with or without bile duct injury. Colonoscopy screens for inflammatory bowel disease. Exclude Wilson disease, viral hepatitis and IgG4-related disease.

Differential diagnosis.

• Autoimmune hepatitis.
• Primary sclerosing cholangitis.
• IgG4-related disease.
• Langerhans cell histiocytosis.
• Cystic fibrosis liver disease.
• Immunodeficiency associated cholangiopathy.

Immunosuppress the hepatitis and give ursodeoxycholic acid.

• Prednisolone: 2 mg/kg orally once daily (maximum 60 mg), tapered over 4 to 8 weeks to a maintenance dose of 2.5 to 5 mg daily or alternate days; maximum 60 mg daily; monitor growth, glucose, blood pressure, bone density and infection; give calcium and vitamin D.
• Azathioprine: 1 to 2 mg/kg orally once daily, added when aminotransferases fall; maintenance for years; maximum 2.5 mg/kg daily; monitor blood counts and liver tests; check thiopurine methyltransferase first; reduce in renal impairment and with allopurinol.
• Ursodeoxycholic acid: 15 to 20 mg/kg orally daily in 2 to 3 divided doses; long term; maximum 20 mg/kg daily; monitor liver tests every 3 months; avoid in complete biliary obstruction.

Treat cholangitis with antibiotics and strictures by endoscopic therapy. Cholangiopathy often progresses even when hepatitis responds. Refer for liver transplantation in progressive disease, noting that sclerosing cholangitis can recur.

Monitoring. Liver tests and IgG monthly at first, then every 3 months; cholangiography every 1 to 2 years; colonoscopy yearly in inflammatory bowel disease.

Referral and escalation. Paediatric hepatology and transplant centre; gastroenterology for inflammatory bowel disease.

Special groups. Adolescents need transition planning to adult hepatology and attention to adherence.