Week 5: Autoimmune liver diseases

Question 1

Autoimmune hepatitis

Answer 1

-immune mediated destruction of hepatocytes
-more females than males
-often associated with other autoimmune disorders
CLINICAL COURSE
-often asymptomatic
-fatigue, arthralgias, fluctuating jaundice
-cirrhosis, acute liver failure, subacute liver failure

Question 2

Diagnosis of AIH

Answer 2

• female, with predominantly hepatocellular injury pattern
• elevated IgG and total global
• response to immunosuppression
• positive autoimmune markers:
• Type 1: ANA, anti-SMA, p-ANCA (assoc. with UC).
• Type 2: anti-LKM1. In children, harder to treat.
• Brighton Criteria: scoring system for diagnosis

Question 3

Treatment of AIH

Answer 3

• Prednisone: start with this +AZA or prednisone alone. Taper steroid within 4 weeks.
• Azathioprine: converted to 6MP in blood. Blocks de novo purine nucleotide synthesis, limits lymphocyte proliferation by impairing cell cycle. Used as maintenance drug.
• liver transplantation

Question 4

Predictors of poor outcome and good response in AIH

Answer 4

POOR
-failure to normalize aminotransferases: relapse and cirrhosis
-degree of plasma cell infiltrate
-HLA DR3: more progressive disease
-African descent
-Type 2 AIH
GOOD
-older age at presentation: HLA DR4
-rapidity of response

Question 5

Drug related AIH

Answer 5

• classic drugs: nitrofurantoin, minocycline, methyldopa

- usually improvement after drug withdrawal and/or immunosuppression

Question 6

Compare primary biliary cirrhosis with primary sclerosing cholangitis

Answer 6

PBC
-F >>M, adults only
-small to medium bile ducts
-assoc. with autoimmune diseases
-has a specific autoantibody, AMA+, also IgM elevated
-complicated by HCC
PSC
-M > F, children
-medium to large bile ducts
-assoc. with IBD
-non-specific autoantibodies
-complicated by cholangiocarcinoma

Question 7

Primary sclerosing cholangitis

Answer 7

• frequently associated with IBD (mainly UC)
• diffuse inflammation, obstruction, and fibrosis of intra and extra hepatic bile ducts
• etiology unknown, immune mediated
• presents in 4th and 5th decade, more males.
• symptoms: none, fatigue, pruritis, pain/fever
• rare to have liver failure/portal HTN presentation

Question 8

Diagnosis of primary sclerosing cholangitis

Answer 8

• multifocal strictures with beading of intrahepatic and or extra hepatic biliary tree
• autoantibiodies are non specific
• exclusion of secondary causes: ischemia, trauma, surgical mishaps, infection, tumor
• labs: AP and GGT elevation. mild to moderate AST/ALT elevation. Elevated bilirubin due to advanced liver disease.
• histo: see onion skinning (fibrosis around bile duct)

Question 9

Natural history of PSC

Answer 9

1. small duct cholangitis
2. progressive cholestasis
3. cirrhosis
4. decompensation
   - median time from dx to death or OLT is 8 years
   - complications: bacterial cholangitis (common after ERCP), cholangiocarcinoma

Question 10

Treatment of PSC

Answer 10

• No therapy prolongs survival except for transplant
• UDCA: improved liver tests with no change in symptoms or histology
• corticosteriods: only if overlap with AIH
• endoscopic Rx for strictures

Question 11

Primary biliary cirrhosis

Answer 11

• 10:1 F:M ratio, median onset 50 yo
• immune mediated intrahepatic bile duct injury, with portal inflammation, necrosis of interlobular and septal bile ducts. progressive destruction leads to bile duct loss and cirrhosis.
• jigsaw cirrhosis
• anti-mitochondrial antibody
• symptoms: fatigue, pruritis, fractures, symptoms of progressive liver failure/portal HTN
• Associations: Sjogren’s syndrome, RTA< gallstones, arthritis, thyroid disease, scleroderma, Raynaud’s

Question 12

Diagnosis of PBC

Answer 12

• cholestatic pattern of disease
• AMA + 95%, directed against 2-oxo-acid dehydrogenase complex
• absent bile duct obstruction
• elevated serum IgM, 50% ANA+

Question 13

Natural history of PBC

Answer 13

1. Silent, pre-clincal
   -AMA+ only, may be decades
2. Asymptomatic phase
   -gradual elevation in AP, 50% symptomatic in 5 years
3. Symptomatic phase
   -median survival 6-10 years
4. Pre-terminal phase
   -progressive jaundice, lasts up to 2 years
   COMPLICATIONS
   -progressive liver failure
   -HCC
   -pruritus
   -bone loss- due to decrease absorption of fat soluble vitamins

Question 14

Treatment of PBC

Answer 14

• UDCA only approved treatment. may delay disease progression and extend OLT free survival
• liver transplant