Autoimmune Diseases of Liver

Question 1

3 Main Diseases and How Does Ea Present?

Answer 1

1- autoimmune hepatitis
2- primary biliary cirrhosis/ cholangitis
3- primary sclerosing cholangitis

usually asymptomatic and found on incidental labs or non-specific symptoms (fatigue, fever, anorexia, ab discomfort, jaundice, mild pruritis) + extrahepatic autoimmune disease (US, sclerosis, Sjogren, arthritis)

Question 2

How do they differ in epidemiology?

Answer 2

AH - mainly white women (types 2/3 more common in european women)

PBC - middle-aged white women

Primary Sclerosing Chol - more common in men and 80% have UC

Question 3

Autoimmune Hepatitis Dx

Answer 3

• REQUIRED BIOPSY
• Histology - interface hepatitis (plasma cells + others from portal tract to interface w/ lobule) w/o lymphoid aggregates or bile duct destruction
• Labs - often hepatocellular pattern of labs (inc ALT/AST) and inc conjugated bilirubin (may also have dec albumin or inc clotting factors)
• Also see auto-antibodies but not specific (ANA, SMA, LKM-1)

Question 4

PBC Dx (include 4 stages)

Answer 4

• Dx - AMA (anti-mito antibodies) is most sensitive and cholestatic labs (inc ALP, GGT)
  
  • Now use specific PDC-E2 antigen of AMA (also known as M2) for diagnosis
• Histology - destructive cholangitis of only intrahepatic bile ducts (interlobular and septal ducts)
  
  • Florid duct lesion (intraepithelial plasma cells and lymphocytes centered around ducts)
  • May have granulomas

4 Stages (for prognosis)

    - 1- florid duct lesion/ intra-hepatic bile duct damage
    - 2- ductular proliferation (spills over into interface)
    - 3- scarring
    - 4- cirrhosis (can lead to pre-sinusoid portal htn b/c fibrosis in tracts b/f sinusoids)

Question 5

Primary Sclerosing Cholangitis Dx

Answer 5

• Cholestatic labs (inc GGT, inc ALP) but can also have 2/3x normal LFTs
• NO DEFINITE SEROLOGICAL TEST (p-ANCA is common but not specific)
• Diagnosis made by cholangiography - see both intrahepatic and extra-hepatic duct fibrosis w/ dilation of normal intervening areas of duct (beads-on-a-string)
  - ERCP (dangerous), percutaneous cholangiography, MRCP
• Histology - BIOPSY NOT REQUIRED; non-specific onion skinning fibrosis around ducts

Question 6

Autoimmune Hepatitis Tx and Prognosis

Answer 6

Indications for Tx - 10X normal AST, 5X normal ALT, 2X inc IgG, severe necrosis (seen as bands of dead hepatocytes - bridging necrosis) or if very symptomatic
- DO NOT TREAT IF ALREADY CIRRHOTIC

• Prednisone or prednisone w/ azathioprine then wean off prednisone w/ time
• Treat steroid side effects - osteoporosis, DM, dec immune function, etc
• Also treat/prevent liver damage like portal HTN, jaundice, ascites, encephalopathy
• Remission = no symptoms, normal biopsy, normal labs (stop tx)
• Live normal life on immunosuppressive therapy; just deal w/ side effects
• May get liver transplant but high rate of rejection b/c autoimmune in nature

Question 7

PBC Tx and Prognosis

Answer 7

TREATMENT

• UDCA (ursodeoxycholic acid)- dec bile acid levels to protect cell membranes
• Immunosuppressive therapy
• Treat pruritus w/ cholestryamine –> rifampin –> alternatives –> liver transplant
• Prevention - bone density tests and monitor vitamins
• Usually asymptomatic for long periods but eventually progresses to cirrhosis
• Other complications - osteoporosis, def in fat-soluble vitamins

Question 8

Primary Sclerosing Cholangitis Tx and Prognosis

Answer 8

• No effective tx; many get liver transplant (if ascites, variceal bleeds, encephalopathy)
• May try endoscopic therapy to remove biliary blockage (balloon, drainage, stent)
• Surgical resection if endoscopic treatment fails
• Progression to death or need for liver transplant in 12-18 yrs
• Poss Complications - cholangiocarcinoma, cholelithiasis –> gall bladder neoplasia, colorectal neoplasia (b/c associated w/ UC)