Autoimmune Hepatitis

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Autoimmune Hepatitis

• Overview
• Diagnosis Treatment

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Liver
Immunity
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Genetic factors
Triggering factors
AIH
Immuno- regulatory
Autoantigens
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Autoimmune Hepatitis(AIH)

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

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AIH
Biochemical
Histological
Gamma globulin Autoantibody
Interface hepatitis Portal plasma cell
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AIH
Biochemical
ANA SMA Anti-LKM1
Gamma globulin Autoantibody
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AIH
Biochemical
ANA SMA Anti-LKM1
Neither pathogenic nor disease specific
Gamma globulin Autoantibody
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AIH
Biochemical
ANA SMA Anti-LKM1
Expression Vary during AIH course Don't
predict histologic injury
Gamma globulin Autoantibody
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AIH
Biochemical
ANA SMA Anti-LKM1
Levels dont reflect treatment response Do not
need monitoring
Gamma globulin Autoantibody
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AIH
Evolving Ab
Conventional Ab
Biochemical
ANA SMA Anti-LKM1
Anti-AGRA Anti-LC1 Anti-SLA/LP pANCA Anti-Actin
Gammaglobulin Autoantibody
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AIH
Histological
Neither is disease specific Absence do not
preclude diagnosis
Interface hepatitis Portal plasma cell
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Liver biopsy?

• Establish diagnosis
• Disease severity
• Need for treatment
• Therapeutic monitoring

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Diagnosis

• Presence
• Biochemical
• Histological

• Exclusion
• Wilson disease
• HCV
• Drugs

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Diagnostic criteria
Laboratory features
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Diagnostic criteria
Auto antibodies
Laboratory features
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Diagnostic criteria
Histological findings
Auto antibodies
Laboratory features
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Diagnostic criteria
No toxic or alcohol injury
Histological findings
Auto antibodies
Laboratory features
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Diagnostic criteria
No active viral infection
No toxic or alcohol injury
Histological findings
Auto antibodies
Laboratory features
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Diagnostic criteria
No genetic liver disease
No active viral infection
No toxic or alcohol injury
Histological findings
Auto antibodies
Laboratory features
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Diagnostic criteria

• Difference between definite probable AIH
• Degree of IGg elevation
• ANA, SMA, anti-LKM1 levels
• Exposures to drugs, alcohol infections
• Presence of evolving reperatoire auto antibodies
  support probable diagnosis

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Diagnostic scoring system
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Diagnostic scoring system
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Diagnostic scoring system

• Definite
• Pre Rx gt15
• Post Rx gt17

• Probable
• Pre Rx 10-15
• Post Rx 12-17

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Recommendations

• Aminotransferase,gamma globulin levels
• ANA /or SMA anti LKM1
• Liver tissue exam

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Recommendations

• AIH diagnostic criteria applied to all patients
• Scoring method if AIH diagnosis is not clear

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Treatment

• Improves
• Symptoms
• Laboratory tests
• Histological findings
• Survival (20y life expectancygt80)

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Liver
Immunity
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Liver
Drugs
Immunity
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Treatment
prednisone
Prednisone azathioprine
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Treatment
prednisone
Prednisone azathioprine
cyclosporine ursodeoxycholic acid FK506 6
mercaptopurine methotrexate cyclophosphamide my
cophenolate mofetil rapamycin
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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

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Who should be treated?
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• Mild disease
• AST/G globulin
• ltabsolute criteria
• Interface hepatitis

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• Mild disease
• AST/G globulin
• ltabsolute criteria
• Interface hepatitis

Benefit-risk ratio undefined
Clinical judgment
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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

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Regimens prednisone
End point
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Regimens prednisone
End point
Cytopenia Thiopurine methyl transferase
deficiency Malignancy
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Regimens prednisoneazathioprine
End point
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Regimens prednisoneazathioprine
End point
Postmenopause Osteoporosis Brittle
DM Obesity Hypertension Emotional lability
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• There is no prescribed minimum or maximum
  duration of treatment
• Therapy should not be instituted with the
  intention of being indefinite

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Treatment End Points
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Pattern of response
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Pattern of response

• No symptoms
• Normal billirubin/glob
• ASTlt2UN
• Normal tissue
• No interface hepatitis

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Treatment failure(9)
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Incomplete response(13)
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Relapse

• Occurs in 20-100
• Depends on histology at end point
• Liver biopsy prior to termination is preferred
  but not essential
• Increase ASTgt3folds
• Increase gamma globulingt2g/dl

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Relapse

• Depends on histology at end point

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Management after relapse

• Indefinite low dose prednisone
• Indefinite azathioprine

87 remission 12 were able to be withdrawn
from medication(6y)
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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)

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Recommendation

• High dose prednisone alone or in combination with
  azathioprine should be used in treatment failure
• Corticosteroids should be considered in the
  decompensated patients
• Liver transplantation should be considered in the
  decompensated patients unsalvaged by drug therapy

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