Auto-Immune Hepatobiliary Disease

“Autoimmune diseases of the liver and biliary system”

• Three diseases include:
  • Autoimmune Hepatitis (AIH)
  • Primary Biliary Cirrhosis/Cholangitis (PBC)
  • Primary Sclerosing Cholangitis (PSC)

Risk Factors

• AIH:
  • Typically common in young women
  • Autoimmune conditions
• PBC:
  • Common in middle-aged women with recurrent UTIs
  • +ve family history
  • Smoking
  • Past pregnancy
• PSC:
  • Common among middle-aged men with ulcerative colitis

Aetiology

• Generally idiopathic
• Commonly associated with other autoimmune conditions – T1DM, Hashimoto’s thyroiditis, coeliac disease
• Genetic predisposition
• Possible environmental triggers

Pathophysiology

• AIH:
  • Abnormal T cell function and autoantibodies directed against hepatocyte surface antigens.
  • Classification by autoantibodies
• PBC:
  1. Inflammation and the progressive destruction of only intrahepatic bile ducts
  2. Defective bile duct regeneration
  3. Chronic cholestasis
  4. Fibrotic changes
  5. Liver failure
• PSC:
  • Progressive chronic inflammation of intrahepatic and extrahepatic bile ducts

Clinical Presentation

• AIH:
  • Acute hepatitis and signs of autoimmune disease – Fatigue, abdominal pain, weight loss, jaundice, RUQ pain, fever
• PBC:
  • Lethargy, sleepiness, and pruritis may precede jaundice by years.
  • Skin pigmentation
  • Xanthomata
  • Hepatosplenomegaly
• PSC:
  • Incidental ↑ ­ALP finding in patient with IBD, pruritis, fatigue, jaundice, hepatomegaly

Investigations

• AIH:
  • ­↑ Serum bilirubin, ­ ↑ AST, ­↑ ALT and ­↑ ALP, hypergammaglobulinaemia, +ve autoantibodies (ASMA, ANA, ­↑ IgG, LKM1). Anaemia, ↓ WCC and ↓ platelets indicate hypersplenism
  • Liver biopsy (mononuclear infiltrate of the portal and periportal areas
• PBC:
  • ­↑ ALP, ↑ ­GGT, ↑­bilirubin, ↓ albumin, ­↑ prothrombin time. 98% are AMA M2 subtype +ve.
  • Ultrasound to exclude extrahepatic cholestasis
• PSC:
  • ­↑ ALP, ↑ ­bilirubin, hypergammaglobulinaemia, ↑ ­IgM, AMA -ve but ANA, SMA and ANCA maybe +ve.
  • ERCP or MRCP to reveal duct anatomy and damage.
  • Liver biopsy shows fibrous obliterative damage

Management

• AIH:
  • Immunosuppressant therapy
    • Prednisolone30mg/d PO for 1 month, ↓ by 5mg a month to a maintenance dose of 5-10mg/d PO.
    • Azathioprine (50-100mg/d PO) used as a steroid-sparing agent to maintain remission.
  • Liver Transplantation in decompensated cirrhosis or failure to medical therapy
• PBC:
  • Colestyramine for pruritis, osteoporosis prevention, Fat-soluble vitamin prophylaxis (vitamin A, D and K), consider high dose ursodeoxycholic acid to improve survival and delay transplantation.
  • Regular monitoring
• PSC:
  • Liver transplantation is the mainstay for end-stage disease, recurrence occurs in up to 30%; 5% graft survival is >60%

Complications

• Liver cirrhosis and portal hypertension
• Osteoporosis
• Malabsorption.
• Cholangiocarcinoma
• Increased risk of hepatocellular, colorectal, pancreatic and gallbladder cancer