Overview Diagnosis & Treatment 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 Biochemical Histological Gamma globulin Autoantibody Interface hepatitis Portal plasma cell

AIH Biochemical ANA SMA Anti-LKM1 Gamma globulin Autoantibody

AIH Biochemical Neither ANA pathogenic nor SMA disease specific Anti-LKM1 Neither pathogenic nor disease specific Gamma globulin Autoantibody

AIH Biochemical Expression Vary during AIH ANA course SMA Anti-LKM1 Expression Vary during AIH course Don't predict histologic injury Gamma globulin Autoantibody

AIH Biochemical Levels don’t reflect treatment ANA response 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? Establish diagnosis Disease severity Need for treatment Therapeutic monitoring

Diagnosis Presence Biochemical Histological Exclusion Wilson disease HCV Drugs

Diagnostic criteria Laboratory features

Diagnostic criteria Auto antibodies Laboratory features

Histological findings Diagnostic criteria Histological findings Auto antibodies Laboratory features

Diagnostic criteria No toxic or alcohol injury Histological findings Auto antibodies Laboratory features

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

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

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

Diagnostic scoring system

Diagnostic scoring system

Diagnostic scoring system Definite Pre Rx : >15 Post Rx: >17 Probable Pre Rx : 10-15 Post Rx: 12-17

Recommendations Aminotransferase,gamma globulin levels ANA &/or SMA – anti LKM1 Liver tissue exam

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

Treatment Improves Symptoms Laboratory tests Histological findings Survival (20y life expectancy>80%)

Liver Immunity

Liver Drugs Immunity

Treatment prednisone Prednisone + azathioprine

Treatment Prednisone prednisone + azathioprine *cyclosporine *ursodeoxycholic acid *FK506 *6 mercaptopurine *methotrexate *cyclophosphamide *mycophenolate mofetil *rapamycin

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

Who should be treated?

<absolute criteria Mild disease AST/G globulin <absolute criteria Interface hepatitis

<absolute criteria Mild disease AST/G globulin <absolute criteria Interface hepatitis Benefit-risk ratio undefined Clinical judgment

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 : prednisone End point

transferase deficiency Regimens : prednisone End point Cytopenia Thiopurine methyl transferase deficiency Malignancy

Regimens prednisone+azathioprine End point

Regimens prednisone+azathioprine End point Postmenopause Osteoporosis Brittle DM Obesity Hypertension Emotional lability

There is no prescribed minimum or maximum duration of treatment Therapy should not be instituted with the intention of being indefinite

Treatment End Points

Pattern of response

Pattern of response No symptoms Normal billirubin/glob AST<2UN Normal tissue No interface hepatitis

Treatment failure (9%)

Incomplete response (13%)

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

Relapse Depends on histology at end point

Management after relapse Indefinite low dose prednisone Indefinite azathioprine *87% remission *12% were able to be withdrawn from medication(6y)

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%)

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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