Gastrointestinal System >
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:
- Inflammation and the progressive destruction of only intrahepatic bile ducts
- Defective bile duct regeneration
- Chronic cholestasis
- Fibrotic changes
- 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
- Immunosuppressant 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