Liver inflammatory diseases II Flashcards
Lectures week I
Name examples of immune cell-mediated liver diseases (5)
- Chronic alcohol-induced hepatitis
- Bacterial/parasitic infection
- Acute viral infection
- Persistent viral infection
- Autoimmune hepatitis
Name examples of autoimmune hepatitis (3)
- Autoimmune hepatitis (AIH-1, 2 and 3)
- Primary biliary cholangitis (PBC)
- Primary sclerosing cholangitis (PSC)
What are the target cells in autoimmune hepatitis (AIH-1, 2 and 3)?
Hepatocytes
Where does primary biliary cholangitis (PBC) occur?
Small bile ducts
Where does primary sclerosing cholangitis (PSC) occur?
Medium bile ducts
In how many percent of the patients is AIH asymptomatic?
~30%
How many percent of AIH patients present with liver cirrhosis at presentation?
~30%
How is AIH diagnosed in the lab? (5)
- High ALT/ALAT
- Raised serum Ig
- High titers of auto-antibodies
- Negative serum test viral hepatitis
- Compatible liver biopsy
How is PBC diagnosed? (2)
- Progressive liver disease
- Molecular mimicry
True or false: AIH and PBC mainly occur in males
False
What are the histopathological hallmarks of AIH? (4)
- Interface hepatitis
- Hepatocyte ballooning
- Hepatocyte necrosis
- Lymphoplasmacytic infiltrate of plasma- and T cells
What are the characteristics of AIH type 1? (3)
- Most common
- ANA+, anti SMA+ (smooth muscle antibody)
- Good response to therapy
What are the characteristics of AIH type 2? (4)
- Anti LKM1 (liver kidney microsomal), anti LC-1 (liver cytosol)
- Predominant in children
- Poor response to treatment
- Cirrhosis at time of diagnosis
What are the characteristics of AIH type 3? (2)
- Anti-SLA/LP (soluble liver antigen/liver-pancreas)
- Good response to therapy
What is the treatment plan for AIH?
Immunosuppression -> prednisone, azathioprine
What are the aims of the AIH treatment plan? (3)
- Reduce inflammation
- Reduce cholestasis
- Reduce fibrosis progression
How many percent of PSC patients are male?
~70%
With which disease is PSC associated?
IBD
How is PSC diagnosed in the lab? (3)
- Elevated alk fos
- Elevated gGT
- Elevated ALAT/ASAT
Why is there no proven therapy for PSC at this point?
Mainly due to the lack of a defined auto-antigen
What are the steps in PSC disease progression? (5)
- PSC (and IBD)
- Cirrhosis
- Decompensation, cholangiocarcinoma (colorectal cancer)
- LTx
- Death
How is PBC diagnosed in the lab? (5)
- Anti-mitochondrial antibodies (AMA) against PDC-E2
- Elevated IgM
- Lymphocytic inflammation small bile duct
- PDC-E2 specific T- and B cells
- Molecular mimicry
What are the steps in the development of autoimmune hepatitis? (4)
- Predisposition
- Initiating event
- Antigen-specific response
- Progressive tissue damage
Which factors play a role in a predisposition for autoimmune hepatitis? (4)
- Genetic susceptibility (HLA-D)
- Hormonal status
- Impaired negative selection of auto reactive T cells
- SH28B variants