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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
Q

Which events can initiate the development of autoimmune hepatitis? (7)

A
  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
Q

Which autoantibodies are found in up to 50% of chronic HBV patients?

27
Q

Anti-LKM-1 autoantibodies have been found in chronic HCB patients. They have been shown to correlate with..? (2)

A
  1. Disease severity
  2. Adverse reactions to interferon treatment
28
Q

What do anti-LKM-1 autoantibodies recognize?

A

Linear epitopes within cytochrome CYP2D6 -> CYP2D6-specific T cells can be found

29
Q

Which antigen specific responses can occur in autoimmune hepatitis? (4)

A
  1. MHC I - CD4+
  2. MHC II - CD8+
  3. Class-switched antibody mediated
  4. Regulatory mechanisms
30
Q

Which are two examples of regulatory mechanisms in antigen specific responses during autoimmune hepatitis?

A
  1. BCL2 regulated apoptosis
  2. Treg Fas/FasL mediated T cell apoptosis
31
Q

How can progressive tissue damage occur in autoimmune hepatitis? (5)

A
  1. Direct action of cytokines
  2. Direct cytotoxicity from CD8+
  3. Antibody-mediated tissue damage
  4. Fas-mediated apoptosis
  5. Perforin/granzyme B
32
Q

Describe an example of antibody-mediated tissue damage in autoimmune hepatitis

A

Hepatocytes from AIH patients carrying IgG on their surface were susceptible to damage by lymphocytes from health individuals

33
Q

Which treatments show the best results thus far in combating autoimmune hepatitis?

A

B-cell depleting antibodies (anti-CD20)

34
Q

What is the main challenge when studying autoimmune hepatitis?

A

Multifactorial disease with genetic and environmental factors -> no good model that mimics disease

35
Q

In short, the characteristics of PBC are..? (4)

A
  1. Immune-mediated
  2. Female
  3. Therapy by Urso (bile acid)
  4. Auto-antigen known
36
Q

In short, the characteristics of PSC are ..? (4)

A
  1. Immune-mediated
  2. Male
  3. No therapy available
  4. PSC-IBD interaction
37
Q

In short, the characteristics of AIH are..? (4)

A
  1. Immune-mediated
  2. Female
  3. Therapy by immunosuppression (typ I)
  4. Auto-antigen known
38
Q

Why do we need alternatives besides liver transplantation? (2)

A
  1. Donor shortage
  2. Quality of donor organs
39
Q

Which factors influence the quality of donor livers? (3)

A
  1. Obesity
  2. Alcohol
  3. Elderly
40
Q

What are possible alternatives for liver transplantation? (4)

A
  1. Living donor liver transplantation
  2. Revive non-transplantable livers
  3. Tissue engineered livers/organoids
  4. (Stem) cell therapy
41
Q

Which technique is used to revive non-transplantable livers?

A

Machine perfusion

42
Q

Which extended donor criteria exist when dealing with a suboptimal graft? (5)

A
  1. Donor age
  2. BMI
  3. DCD
  4. > max time circulation arrest
  5. Increased liver enzymes
43
Q

Why is graft optimalization important?

A

Reduction of ischemia

44
Q

How can you optimalize the graft? (2)

A
  1. Static cold storage donor livers
  2. Dynamic liver preservation techniques
45
Q

Dynamic liver preservation techniques are performed via two ways…

A
  1. Hypothermic (4-10 degrees)
  2. Normothermic (37 degrees)
46
Q

Which dynamic liver preservation way is used in clinical trials?

A

Normothermic (37 degrees) -> more physiological

47
Q

What is the goal of tissue engineering in the liver transplantation field?

A

To create new tissue/cells to heal organs or to create an entirely new organ

48
Q

Which issues arise using engineered liver tissue? (4)

A
  1. Toxicological studies
  2. Drug testing
  3. Disease modeling
  4. Clinical applications
49
Q

Which functional liver tissues are used in vitro? (4)

A
  1. Parenchymal cells
  2. Stromal cells
  3. Scaffold
  4. Biologicals
50
Q

What can we do if the graft is in a really bad shape (as opposed to a suboptimal shape)?

A

Make a graft scaffold

51
Q

What are the steps of making a graft scaffold? (4)

A
  1. Decellularization -> detergent perfusion
  2. Recellularization -> liver cell infusion
  3. Revascularization -> endothelial cell infusion
  4. Functional liver graft
52
Q

Which factors are essential for decellularization? (3)

A
  1. No cells
  2. ECM proteins unaffected
  3. Liver architecture remained (vascular- and biliary system)
53
Q

CARD ABOUT BILLARY SYSTEM

54
Q

What is the main challenge when using a decellularized liver?

A

Liver does not trigger the immune system -> HLA proteins are absent

55
Q

For what do you stain to determine if ECM proteins are unaffected? (2)

A
  1. Collagen
  2. Elastin
56
Q

CHECK SLIDES VANAF HIER EVEN

57
Q

From which cells are organoids derived? (4)

A
  1. (Pluripotent) stem cells
  2. Primary cells
  3. Stem/progenitor cells
  4. Progenitor/differentiated cells
58
Q

What are two important qualities of organoids?

A
  1. Self-organization
  2. Recapitulation of aspects of native tissue
59
Q

How do organoids self organize?

A
  1. Cell-cell interactions
  2. Cell-matrix interactions

I&I WC2 (22 decks)

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