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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

slide2

Liver

Immunity

slide3

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.
slide5
AIH

Biochemical

Histological

Gamma globulin

Autoantibody

Interface hepatitis

Portal plasma cell

slide6
AIH

Biochemical

ANA

SMA

Anti-LKM1

Gamma globulin

Autoantibody

slide7
AIH

Biochemical

ANA

SMA

Anti-LKM1

Neither

pathogenic nor

disease specific

Gamma globulin

Autoantibody

slide8
AIH

Biochemical

ANA

SMA

Anti-LKM1

Expression

Vary during AIH

course

Don\'t predict

histologic injury

Gamma globulin

Autoantibody

slide9
AIH

Biochemical

ANA

SMA

Anti-LKM1

Levels don’t

reflect treatment

response

Do not need

monitoring

Gamma globulin

Autoantibody

slide10
AIH

Conventional Ab

Evolving Ab

Biochemical

ANA

SMA

Anti-LKM1

Anti-AGRA

Anti-LC1

Anti-SLA/LP

pANCA

Anti-Actin

Gammaglobulin

Autoantibody

slide11
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%)
slide26

Liver

Immunity

slide27

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
slide32

Mild disease

  • AST/G globulin
  • <absolute criteria
  • Interface hepatitis
slide33

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 azathioprine1
Regimens prednisone+azathioprine

End point

Postmenopause

Osteoporosis

Brittle DM

Obesity

Hypertension

Emotional lability

slide39
There is no prescribed minimum or maximum duration of treatment
  • Therapy should not be instituted with the intention of being indefinite
pattern of response1
Pattern of response
  • No symptoms
  • Normal billirubin/glob
  • AST<2UN
  • Normal tissue
  • No interface hepatitis
relapse
Relapse

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
  • Depends on histology at end point
management after relapse
Management after relapse
  • Indefinite low dose prednisone
  • Indefinite azathioprine

*87% remission

*12% were able to be withdrawn from medication(6y)

liver transplantation
Liver transplantation
  • 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%)
ad