Autoimmune hepatitis
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Autoimmune Hepatitis. Overview Diagnosis & Treatment. Liver. Immunity. Genetic factors. Triggering factors. AIH. Immuno- regulatory. Autoantigens. Autoimmune Hepatitis (AIH). Unresolving inflammation of the liver characterized by a loss of tolerance against hepatic tissue. AIH.

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Presentation Transcript
Autoimmune hepatitis

Autoimmune Hepatitis

Overview

Diagnosis & Treatment


Liver

Immunity


Genetic

factors

Triggering

factors

AIH

Immuno-

regulatory

Autoantigens


Autoimmune hepatitis aih
Autoimmune Hepatitis(AIH)

  • Unresolving inflammation of the liver characterized by a loss of tolerance against hepatic tissue.


AIH

Biochemical

Histological

Gamma globulin

Autoantibody

Interface hepatitis

Portal plasma cell


AIH

Biochemical

ANA

SMA

Anti-LKM1

Gamma globulin

Autoantibody


AIH

Biochemical

ANA

SMA

Anti-LKM1

Neither

pathogenic nor

disease specific

Gamma globulin

Autoantibody


AIH

Biochemical

ANA

SMA

Anti-LKM1

Expression

Vary during AIH

course

Don't predict

histologic injury

Gamma globulin

Autoantibody


AIH

Biochemical

ANA

SMA

Anti-LKM1

Levels don’t

reflect treatment

response

Do not need

monitoring

Gamma globulin

Autoantibody


AIH

Conventional Ab

Evolving Ab

Biochemical

ANA

SMA

Anti-LKM1

Anti-AGRA

Anti-LC1

Anti-SLA/LP

pANCA

Anti-Actin

Gammaglobulin

Autoantibody


AIH

Histological

Neither is

disease specific

Absence do

not preclude

diagnosis

Interface hepatitis

Portal plasma cell


Liver biopsy
Liver biopsy?

  • Establish diagnosis

  • Disease severity

  • Need for treatment

  • Therapeutic monitoring


Diagnosis

Presence

Biochemical

Histological

Exclusion

Wilson disease

HCV

Drugs

Diagnosis


Diagnostic criteria
Diagnostic criteria

Laboratory features


Diagnostic criteria1
Diagnostic criteria

Auto antibodies

Laboratory features


Diagnostic criteria2
Diagnostic criteria

Histological findings

Auto antibodies

Laboratory features


Diagnostic criteria3
Diagnostic criteria

No toxic or alcohol injury

Histological findings

Auto antibodies

Laboratory features


Diagnostic criteria4
Diagnostic criteria

No active viral infection

No toxic or alcohol injury

Histological findings

Auto antibodies

Laboratory features


Diagnostic criteria5
Diagnostic criteria

No genetic liver disease

No active viral infection

No toxic or alcohol injury

Histological findings

Auto antibodies

Laboratory features




Diagnostic scoring system2

Definite

Pre Rx : >15

Post Rx: >17

Probable

Pre Rx : 10-15

Post Rx: 12-17

Diagnostic scoring system


Recommendations
Recommendations

  • Aminotransferase,gamma globulin levels

  • ANA &/or SMA – anti LKM1

  • Liver tissue exam


Recommendations1
Recommendations

  • AIH diagnostic criteria applied to all patients

  • Scoring method if AIH diagnosis is not clear


Treatment
Treatment

  • Improves

  • Symptoms

  • Laboratory tests

  • Histological findings

  • Survival (20y life expectancy>80%)


Liver

Immunity


Liver

Drugs

Immunity


Treatment1
Treatment

prednisone

Prednisone

+

azathioprine


Treatment2
Treatment

prednisone

Prednisone

+

azathioprine

*cyclosporine *ursodeoxycholic acid *FK506

*6 mercaptopurine *methotrexate *cyclophosphamide

*mycophenolate mofetil *rapamycin


Who should be treated
Who should be treated?

  • Severe disease progress to cirrhosis in 82% within 5 years & mortality is 45%

  • Mild/moderate disease progress to cirrhosis in 49% within 15 years & a 10 years survival of 90%

  • Untreated patients with interface hepatitis have 17% probability of cirrhosis within 5 years and normal 5 years life expectancy



  • Mild disease

  • AST/G globulin

  • <absolute criteria

  • Interface hepatitis


  • Mild disease

  • AST/G globulin

  • <absolute criteria

  • Interface hepatitis

Benefit-risk ratio

undefined

Clinical judgment


Recommendation
Recommendation

  • Severe disease

  • Symptomatic disease

  • Interface hepatitis alone does not compel treatment

  • Treatment not indicated in patients with inactive cirrhosis, preexistent comorbid conditions

  • Treatment in most children



Regimens prednisone1
Regimens : prednisone

End point

Cytopenia

Thiopurine methyl

transferase deficiency

Malignancy


Regimens prednisone azathioprine
Regimens prednisone+azathioprine

End point


Regimens prednisone azathioprine1
Regimens prednisone+azathioprine

End point

Postmenopause

Osteoporosis

Brittle DM

Obesity

Hypertension

Emotional lability





Pattern of response1
Pattern of response treatment

  • No symptoms

  • Normal billirubin/glob

  • AST<2UN

  • Normal tissue

  • No interface hepatitis


Treatment failure 9
Treatment failure treatment(9%)


Incomplete response 13
Incomplete response treatment(13%)


Relapse
Relapse treatment

Occurs in 20-100%

Depends on histology at end point

Liver biopsy prior to termination is preferred but not essential

Increase AST>3folds

Increase gamma globulin>2g/dl


Relapse1
Relapse treatment

  • Depends on histology at end point


Management after relapse
Management after relapse treatment

  • Indefinite low dose prednisone

  • Indefinite azathioprine

*87% remission

*12% were able to be withdrawn from medication(6y)


Liver transplantation
Liver transplantation treatment

  • Indicated if deterioration occurs during or after corticosteroid treatment (10%)

  • 5 year patient & graft survival 83-92%

  • Auto antibodies disappear within 1y

  • Disease recurrence is mild (10-35%)


thanks treatment


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