Autoimmune Liver Disease Flashcards
Give examples of autoimmune liver disease.
Primary biliary cholangitis (PBC)
Primary sclerosing cholangitis (PSC)
Autoimmune hepatitis
What is PBC?
Interlobular bile ducts are damaged by chronic autoimmune granulomatous inflammation causing cholestasis which may lead to fibrosis, cirrhosis and portal HTN.
Cause of PBC.
Unknown environmental triggers + genetic predisposition leading to loss of immune tolerance to self-mitochondrial proteins.
What is the hallmark antibody for PBC?
Antimitochondrial antibodies (AMA)
Prevalence of PBC.
<4/100000
Female 9:1 Male
Risk factors of PBC.
+ve FH
Many UTIs
Smoking
Past pregnancy
Other autoimmune conditions
Use of nail polish and hair dye.
Typical age of presentation of PBC.
50 years old
Clinical features of PBC.
Usually asymptomatic and diagnosed after incidental finding of increased ALP.
Lethargy, sleepiness and pruritus may precede jaundice by years.
Jaundice
Skin pigmentation
Xanthelasma
Xanthoma
Hepatosplenomegaly
Complications of PBC.
Cirrhotic complications
Osteoporosis
Malabsorption of fat-soluble vitamins (A, D, E, K) due to the cholestasis
Osteomalacia
Coagulopathy
HCC
Blood test findings in PBC.
Increased ALP and gamma GT
Mildly increased or normal AST and ALT
Increase in bilirubin and decrease in albumin.
Increase in prothrombin time.
AMA +ve
Other autoantibodies might be present.
Immunoglobulins are increased and especially IgM
TSH and cholesterol might be increased or normal
Why might you do an ultrasound in PBC?
To exclude extrahepatic cholestasis.
Biopsy findings in PBC.
This is usually not needed unless drug-induced cholestasis or hepatic sarcoidosis needs to be excluded.
Granulomas around the bile ducts and cirrhosis can be present.
Treatment of PBC.
Treat the symptoms;
Pruritus - try colestyramine 4-8g/24h PO, naltrexone or rifampicin
Diarrhoea - codeine phosphate 30mg/8h PO
Osteoporosis management
Give fat-soluble vitamin prophylaxis of A, D, E and K.
Consider high-dose ursodeoxycholic acid which can improve survival and delay transplantation.
Monitoring of PBC.
Regular LFTs
Ultraound and AFP twice yearly if cirrhotic
Indications for liver transplantation in PBC.
End-stage disease or intractable pruritus.
Prognosis of PBC.
Highly variable
Mayo survival model is a validated predictor of survival that combines age, bilirubin, albumin, PT time, oedema and need for diuretics.
What is primary sclerosing cholangitis? (PSC)
Progressive cholestasis with bile duct inflammation and strictures.
Clinical features of PSC.
Jaundice
Chronic right upper quadrant pain
Pruritus
Fatigue
Hepatomegaly
If it is advanced you might see ascending cholangitis, cirrhosis and hepatic failure.
Associations of PSC.
Male sex
HLA-A1, B8, DR3
Autoimmune hepatitis
80% of northern europena patients also have IBD (usually UC)
Cancer risks in PSC.
Bileduct cancer
Gallbladder cancer
Liver cancer
Colon cancer
How are cancers in PSC monitored?
Yearly colonscopy and ultrasound
Consider doing a cholecystectomy for gallblader polyps.
Test findings in PSC.
Increased ALP and bilirubin
Hypergammaglobulinaemia
Increased IgM
AMA -ve
Can be ANA, SMA or ANCA positive.
Gold standard investigation for diagnosis of PSC
MRCP
Will show bile duct lesions and strictures
Findings on ERCP or MRCP in PSC.
Abnormal duct anatomy and damage.
It can show strictures and a characteristc beaded appearance.
MRCP might show intrahepatic ducts with multifocal strictures.
These strictures might be hard to distinguish from cholangiocarcinoma.
Treatment of PSC.
Ursodeoxyholic acid can improve LFTs but has not shown evidence of survival benefit. High doses may also be harmful, which separates this from PBC.
ERCP to dilate and stent any strictures
Colestryamine for pruritus or naltrexone or rifampicin.
Monitor for any complications
Antibiotics for bacterial cholangitis.
Liver transplant (curative)
Indications for liver transplant in PSC.
It is the mainstay treatment for end-stage disease and will eventually be required.
Findings on liver biopsy of PSC.
Fibrous obliterative cholangitis
What is autoimmune hepatitis (AIH)?
An inflammatory liver disease of unknown cause.
It is characterised by abnormal T-cell function and autoantibodies directed against hepatocyte surface antigens.
How is classification of AIH done?
By autoantibodies
Types of autoimmune hepatitis.
Type I
Type II
What is type I AIH?
Seen in 80%
Typical patient is female and less than 40
They are antismooth muscle antibody (ASMA) positive in 80% of cases.
ANA +ve in 10% of cases
IgG is increased in 97% of cases
They have a good response to immunosuppression and 25% have cirrhosis at presentation.
What is type II AIH?
Commoner in Europe than USA.
More often seen in children and more commonly progresses to cirrhosis and less treatable.
Typically anti-liver/kidney microsomal type 1 (LKM1) antibody positive.
Anti-liver cytosol antigen type 1 (anti-LC1)
ASMA and ANA negative
Epidemiology of AIH.
Predominantly affects young or middle aged women.
They are either 10-30 yo or over 40.
Clinical features of AIH.
40% present with acute hepatitis and signs of autoimmune disease such as fever, malaise, urticarial rash, polyarthritis, pleurisy, pulmonary infiltrations and glomerulonephritis.
The remaining 60% present with gradual jaundice or are asymptomatic and diagnosed incidentally with signs of chronic liver disease.
Amenorrhoea is common.
Complications of AIH.
Those of cirrhosis + drug therapy
Test findings in AIH.
Serum bilirubin, ALT, AST and ALP increased
Hypergammaglobulinaemia
+ve for autoantibodies (ASMA or LKM1)
Anaemia
Reduced WCC
Reduced platelets
Findings on biopsy of AIH.
Mononuclear infiltrate of portal and periportal areas
Piecemeal necrosis +/- fibrosis
Cirrhosis
What is MRCP used for in AIH?
Helps exclude PSC if ALP is increased disproportionately
Diagnosis of AIH.
Depends on excluding other diseases.
Diagnostic critera based on IgG levels, autoantibodies and histology in absence of viral disease are helpful.
Sometimes there can be an overlap with other chronic liver diseases like PBC and PSC as well as chronic viral hepatitis, this makes diagnosing more challenging.
Biopsy can confirm
Management of AIH.
Immunosuppressant therapy
Liver transplantation
Explain immunosuppressant therapy of AIH.
Prednisolone 30mg/d PO for 1 month and then decrease by 5mg a month to a maintenance dose of 5-10 mg/d PO.
Prednisolone can be stopped after 2 years, however relapse occurs in 50-86%
Azathioprine 50-100mg/d PO can be used as steroid sparing to maintain remission.
Indications of liver transplantation in AIH.
Decompensated cirrhosis
Failure to respond to medical therapy
Even though liver transplantation is performed recurrence can happen.
Overlap syndromes of AIH.
AIH-PBC
AIH-AIC (autoimmune cholangitis)
Associations of AIH.
Pernicious anaemia
UC
Glomerulonephritis
Autoimmune thyroiditis
Autoimmune haemolysis
DM
PSC
HLA A1, B8 and DR3 haplotypes
