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I&I WC2 > Liver inflammatory diseases II > Flashcards

Liver inflammatory diseases II Flashcards

Lectures week I

1
Q

Name examples of immune cell-mediated liver diseases (5)

A
  1. Chronic alcohol-induced hepatitis
  2. Bacterial/parasitic infection
  3. Acute viral infection
  4. Persistent viral infection
  5. Autoimmune hepatitis
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2
Q

Name examples of autoimmune hepatitis (3)

A
  1. Autoimmune hepatitis (AIH-1, 2 and 3)
  2. Primary biliary cholangitis (PBC)
  3. Primary sclerosing cholangitis (PSC)
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3
Q

What are the target cells in autoimmune hepatitis (AIH-1, 2 and 3)?

A

Hepatocytes

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4
Q

Where does primary biliary cholangitis (PBC) occur?

A

Small bile ducts

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5
Q

Where does primary sclerosing cholangitis (PSC) occur?

A

Medium bile ducts

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6
Q

In how many percent of the patients is AIH asymptomatic?

A

~30%

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7
Q

How many percent of AIH patients present with liver cirrhosis at presentation?

A

~30%

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8
Q

How is AIH diagnosed in the lab? (5)

A
  1. High ALT/ALAT
  2. Raised serum Ig
  3. High titers of auto-antibodies
  4. Negative serum test viral hepatitis
  5. Compatible liver biopsy
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9
Q

How is PBC diagnosed? (2)

A
  1. Progressive liver disease
  2. Molecular mimicry
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10
Q

True or false: AIH and PBC mainly occur in males

A

False

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11
Q

What are the histopathological hallmarks of AIH? (4)

A
  1. Interface hepatitis
  2. Hepatocyte ballooning
  3. Hepatocyte necrosis
  4. Lymphoplasmacytic infiltrate of plasma- and T cells
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12
Q

What are the characteristics of AIH type 1? (3)

A
  1. Most common
  2. ANA+, anti SMA+ (smooth muscle antibody)
  3. Good response to therapy
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13
Q

What are the characteristics of AIH type 2? (4)

A
  1. Anti LKM1 (liver kidney microsomal), anti LC-1 (liver cytosol)
  2. Predominant in children
  3. Poor response to treatment
  4. Cirrhosis at time of diagnosis
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14
Q

What are the characteristics of AIH type 3? (2)

A
  1. Anti-SLA/LP (soluble liver antigen/liver-pancreas)
  2. Good response to therapy
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15
Q

What is the treatment plan for AIH?

A

Immunosuppression -> prednisone, azathioprine

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16
Q

What are the aims of the AIH treatment plan? (3)

A
  1. Reduce inflammation
  2. Reduce cholestasis
  3. Reduce fibrosis progression
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17
Q

How many percent of PSC patients are male?

A

~70%

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18
Q

With which disease is PSC associated?

A

IBD

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19
Q

How is PSC diagnosed in the lab? (3)

A
  1. Elevated alk fos
  2. Elevated gGT
  3. Elevated ALAT/ASAT
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20
Q

Why is there no proven therapy for PSC at this point?

A

Mainly due to the lack of a defined auto-antigen

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21
Q

What are the steps in PSC disease progression? (5)

A
  1. PSC (and IBD)
  2. Cirrhosis
  3. Decompensation, cholangiocarcinoma (colorectal cancer)
  4. LTx
  5. Death
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22
Q

How is PBC diagnosed in the lab? (5)

A
  1. Anti-mitochondrial antibodies (AMA) against PDC-E2
  2. Elevated IgM
  3. Lymphocytic inflammation small bile duct
  4. PDC-E2 specific T- and B cells
  5. Molecular mimicry
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23
Q

What are the steps in the development of autoimmune hepatitis? (4)

A
  1. Predisposition
  2. Initiating event
  3. Antigen-specific response
  4. Progressive tissue damage
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24
Q

Which factors play a role in a predisposition for autoimmune hepatitis? (4)

A
  1. Genetic susceptibility (HLA-D)
  2. Hormonal status
  3. Impaired negative selection of auto reactive T cells
  4. SH28B variants
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25
Which events can initiate the development of autoimmune hepatitis? (7)
1. Viral infection 2. Toxic liver damage 3. Molecular mimicry 4. Neoantigen formation 5. Bystander activation 6. Epitope spreading 7. Hepatic trapping of activated cells
26
Which autoantibodies are found in up to 50% of chronic HBV patients?
ANA & SMA
27
Anti-LKM-1 autoantibodies have been found in chronic HCB patients. They have been shown to correlate with..? (2)
1. Disease severity 2. Adverse reactions to interferon treatment
28
What do anti-LKM-1 autoantibodies recognize?
Linear epitopes within cytochrome CYP2D6 -> CYP2D6-specific T cells can be found
29
Which antigen specific responses can occur in autoimmune hepatitis? (4)
1. MHC I - CD4+ 2. MHC II - CD8+ 3. Class-switched antibody mediated 4. Regulatory mechanisms
30
Which are two examples of regulatory mechanisms in antigen specific responses during autoimmune hepatitis?
1. BCL2 regulated apoptosis 2. Treg Fas/FasL mediated T cell apoptosis
31
How can progressive tissue damage occur in autoimmune hepatitis? (5)
1. Direct action of cytokines 2. Direct cytotoxicity from CD8+ 3. Antibody-mediated tissue damage 4. Fas-mediated apoptosis 5. Perforin/granzyme B
32
Describe an example of antibody-mediated tissue damage in autoimmune hepatitis
Hepatocytes from AIH patients carrying IgG on their surface were susceptible to damage by lymphocytes from health individuals
33
Which treatments show the best results thus far in combating autoimmune hepatitis?
B-cell depleting antibodies (anti-CD20)
34
What is the main challenge when studying autoimmune hepatitis?
Multifactorial disease with genetic and environmental factors -> no good model that mimics disease
35
In short, the characteristics of PBC are..? (4)
1. Immune-mediated 2. Female 3. Therapy by Urso (bile acid) 4. Auto-antigen known
36
In short, the characteristics of PSC are ..? (4)
1. Immune-mediated 2. Male 3. No therapy available 4. PSC-IBD interaction
37
In short, the characteristics of AIH are..? (4)
1. Immune-mediated 2. Female 3. Therapy by immunosuppression (typ I) 4. Auto-antigen known
38
Why do we need alternatives besides liver transplantation? (2)
1. Donor shortage 2. Quality of donor organs
39
Which factors influence the quality of donor livers? (3)
1. Obesity 2. Alcohol 3. Elderly
40
What are possible alternatives for liver transplantation? (4)
1. Living donor liver transplantation 2. Revive non-transplantable livers 3. Tissue engineered livers/organoids 4. (Stem) cell therapy
41
Which technique is used to revive non-transplantable livers?
Machine perfusion
42
Which extended donor criteria exist when dealing with a suboptimal graft? (5)
1. Donor age 2. BMI 3. DCD 4. >max time circulation arrest 5. Increased liver enzymes
43
Why is graft optimalization important?
Reduction of ischemia
44
How can you optimalize the graft? (2)
1. Static cold storage donor livers 2. Dynamic liver preservation techniques
45
Dynamic liver preservation techniques are performed via two ways...
1. Hypothermic (4-10 degrees) 2. Normothermic (37 degrees)
46
Which dynamic liver preservation way is used in clinical trials?
Normothermic (37 degrees) -> more physiological
47
What is the goal of tissue engineering in the liver transplantation field?
To create new tissue/cells to heal organs or to create an entirely new organ
48
Which issues arise using engineered liver tissue? (4)
1. Toxicological studies 2. Drug testing 3. Disease modeling 4. Clinical applications
49
Which functional liver tissues are used in vitro? (4)
1. Parenchymal cells 2. Stromal cells 3. Scaffold 4. Biologicals
50
What can we do if the graft is in a really bad shape (as opposed to a suboptimal shape)?
Make a graft scaffold
51
What are the steps of making a graft scaffold? (4)
1. Decellularization -> detergent perfusion 2. Recellularization -> liver cell infusion 3. Revascularization -> endothelial cell infusion 4. Functional liver graft
52
Which factors are essential for decellularization? (3)
1. No cells 2. ECM proteins unaffected 3. Liver architecture remained (vascular- and biliary system)
53
CARD ABOUT BILLARY SYSTEM
54
What is the main challenge when using a decellularized liver?
Liver does not trigger the immune system -> HLA proteins are absent
55
For what do you stain to determine if ECM proteins are unaffected? (2)
1. Collagen 2. Elastin
56
CHECK SLIDES VANAF HIER EVEN
57
From which cells are organoids derived? (4)
1. (Pluripotent) stem cells 2. Primary cells 3. Stem/progenitor cells 4. Progenitor/differentiated cells
58
What are two important qualities of organoids?
1. Self-organization 2. Recapitulation of aspects of native tissue
59
How do organoids self organize?
1. Cell-cell interactions 2. Cell-matrix interactions
60

I&I WC2 (16 decks)

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