Autoimmune liver disease Flashcards
Characteristic histopathology in autoimmune hepatitis?
Lymphoplasmacytic infiltrate
Hepatic necrosis
Rosetting of liver cells
Interface hepatitis
Which 5 drugs can classically cause an acute hepatitis?
Minocycline Nitrofurantoin Isoniazid Propylthiouracil Methyldopa
Anti-SMA seen in?
What is the antigen?
Seen in autoimmune hepatitis. Antigen is cytoskeletal components
Also seen in hepatitis C and PBC
Seen in 80% autoimmune hep type 1
Which Ab to check for autoimmune hepatitis?
ANA (70-80% but nonspecific)
Anti SMA - AIH-1 80%
Anti LKM1 - AIH-2 (99%)- target CYP2D6; cross reacts with HCV
Anti-LKM3- AIH-2 (10%)
Anti-ASGPR - AIH both (90% but nonspecific)
Treat autoimmune hepatitis?
Pred and when ALT coming down add in AZA
If AZA intolerant, give MMF
If cirrhosis or high risk of pred related complications like diabetes, obesity, osteopaenia- give budesonide in place of pred.
Explain AZA metabolism to yourself; so you know it well.
AZA is metabolised to 6-MP.
6-MMP levels correlate with risk of transaminase elevation but not with efficacy. (high levels have led to hepatotox and occas myelotoxicity)
TGN levels correlate with therapeutic efficacy AND risk of myelotoxicity (aim for above 230-260)
TPMP enzyme activity correlates directly with 6-MMP levels and inversely with 6-TGN levels.
If check TPMT genotype this is cost effective, minimises the risk of leukopaenia, and can go to full dose immediately.
When would you use metabolite testing in IBD?
If NOT RESPONDING to standard doses of thiopurines.
Low/absent 6-TGN and low/absent 6-MMP; non compliance
Low 6-TGN and low 6-MMP; under dosing
Low 6-TGN/ high 6-MMP; thiopurine resistance and consider allopurinol
Both high; thiopurine refractory and change drug
What are the lab findings in PBC?
histo?
Cholestatic LFT High IgM High lipids AMA positive in 95%(!!!!!!) ANA positive in 30%
If AMA negative, may be anti-GP210 or anti-SP100
Look for evidence of other autoimmune disease
Histo: GRANULOMAS, damage to bile ducts
(granulomas also seen in TB, sarcoid, hep B, allopuinol)
How does PBC present?
Fatigue and pruritis in a middle aged woman
Treatment for PBC?
Itch: cholestyramine, antihistamines, rifampicin
Ursodeoxycholic acid
?liver transplant
Follow for complications: osteoporosis, fat soluble vit deficiency, lipid problems, other autoimmune problems
What is the testing like in PSC?
LFTs obstructive picture; ALT and AST 2-3 x ULN
MRCP done; beads on string appearance- if long strictures, worrying for cholangioCa
positive ANCA in 80%
ANA and anti SM Ab in 20-50%
Hypergammaglobulinaemia in half with most in IgM
Should also get an IgG4 level- if IgG4 realted disease then may have a more rapidly progressive course and less likely to respond to steroids
Remember 75% IBD
NEED LIVER BIOPSY FOR MAKING A DIAGNOSIS OF SMALL DUCT PSC WHEN CHOLANGIOGRAPHY IS NORMAL
What is the PSC treatment?
Some treat with ursodeoxycholic acid which improves LFTs but not outcomes
May need transplant.
Histo in PSC?
Histo shows PSC bile duct with ONION RINGS due to fibrosis.
Path hallmark is fibro-oblitteration but uncommon,
often see periductal fibrosis, infiltration, bile duct proliferation
What cancer screening is needed in PSC?
Yearly GB ultrasound
Yearly ERCP for strictures suspicious for cholangioCa + Ca 19.9
Periodic colonoscopy in patients with concomitant UC
Autoimmune hep, PBS, PSC compare histo findings
PBC:
- small interlobular bile duct damage
- eosinophils ++ in the portal tracts
- granulomas
PSC:
- Onion ring formation
- Diffuse bile duct proliferation
- atrophy of bile duct epithelium and obliteration of lumen
- some portal eosinophils
AIH
- interface hepatitis; inflamm cells in portal spill into liver parenchyma
- rosette formation of hepatocytes
- plasma cell rich portal inflammation
