Embed Size (px)
Citation preview
Autoimmune HepatitisAutoimmune Hepatitis
OverviewOverview
Diagnosis & TreatmentDiagnosis & Treatment
Liver
Immunity
AIH
AutoantigensImmuno-
regulatory
Geneticfactors
Triggeringfactors
Autoimmune HepatitisAutoimmune Hepatitis(AIH)(AIH)
Unresolving inflammation of the liver Unresolving inflammation of the liver characterized by a loss of tolerance characterized by a loss of tolerance against hepatic tissue.against hepatic tissue.
AIHAIH
Biochemical Histological
Gamma globulinAutoantibody
Interface hepatitisPortal plasma cell
AIHAIH
Biochemical
Gamma globulinAutoantibody
ANASMA
Anti-LKM1
AIHAIH
Biochemical
Gamma globulinAutoantibody
ANASMA
Anti-LKM1
Neither pathogenic nordisease specific
AIHAIH
Biochemical
Gamma globulinAutoantibody
ANASMA
Anti-LKM1
Expression Vary during AIH
courseDon't predict
histologic injury
AIHAIH
Biochemical
Gamma globulinAutoantibody
ANASMA
Anti-LKM1
Levels don’t reflect treatment
responseDo not needmonitoring
AIHAIH
Biochemical
GammaglobulinAutoantibody
ANASMA
Anti-LKM1
Anti-AGRAAnti-LC1
Anti-SLA/LPpANCA
Anti-Actin
Evolving AbConventional Ab
AIHAIH
Histological
Interface hepatitisPortal plasma cell
Neither is disease specific
Absence do not preclude
diagnosis
Liver biopsy?Liver biopsy?
Establish diagnosisEstablish diagnosisDisease severityDisease severityNeed for treatmentNeed for treatmentTherapeutic monitoring Therapeutic monitoring
DiagnosisDiagnosis
Presence Presence BiochemicalBiochemical Histological Histological
Exclusion Exclusion Wilson diseaseWilson disease HCVHCV Drugs Drugs
Diagnostic criteriaDiagnostic criteria
Laboratory features
Diagnostic criteriaDiagnostic criteria
Laboratory features
Auto antibodies
Diagnostic criteriaDiagnostic criteria
Laboratory features
Auto antibodies
Histological findings
Diagnostic criteriaDiagnostic criteria
Laboratory features
Auto antibodies
Histological findings
No toxic or alcohol injury
Diagnostic criteriaDiagnostic criteria
Laboratory features
Auto antibodies
Histological findings
No toxic or alcohol injury
No active viral infection
Diagnostic criteriaDiagnostic criteria
Laboratory features
Auto antibodies
Histological findings
No toxic or alcohol injury
No active viral infection
No genetic liver disease
Diagnostic scoring systemDiagnostic scoring system
Rxresponse
HLA
histology
AGRA
AutoID
alcohol
serology
AutoAb
IGg
Alk/ASTgender
PLUS
Diagnostic scoring systemDiagnostic scoring system
histology
alcohol
serology
drugs
AMA
Alk/AST
MINUS
Diagnostic scoring systemDiagnostic scoring system
DefiniteDefinite Pre Rx : >15Pre Rx : >15 Post Rx: >17 Post Rx: >17
ProbableProbable Pre Rx : 10-15Pre Rx : 10-15 Post Rx: 12-17Post Rx: 12-17
RecommendationsRecommendations
Aminotransferase,gamma globulin Aminotransferase,gamma globulin levelslevels
ANA &/or SMA – anti LKM1ANA &/or SMA – anti LKM1Liver tissue examLiver tissue exam
Recommendations Recommendations
AIH diagnostic criteria applied to all AIH diagnostic criteria applied to all patientspatients
Scoring method if AIH diagnosis is Scoring method if AIH diagnosis is not clearnot clear
Treatment Treatment
Improves Improves o SymptomsSymptomso Laboratory testsLaboratory testso Histological findingsHistological findingso Survival (20y life Survival (20y life
expectancy>80%)expectancy>80%)
Liver
Immunity
Liver
Immunity
Drugs
Treatment Treatment
prednisonePrednisone
+azathioprine
Treatment Treatment
prednisonePrednisone
+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 Severe disease progress to cirrhosis in 82% within 5 years82% within 5 years & mortality is 45% & mortality is 45%
Mild/moderate disease progress to Mild/moderate disease progress to cirrhosis in cirrhosis in 49% within 15 years49% within 15 years & a & a 10 years survival of 90%10 years survival of 90%
Untreated patients with interface Untreated patients with interface hepatitis have hepatitis have 17% probability of 17% probability of cirrhosis within 5 yearscirrhosis within 5 years and normal 5 and normal 5 years life expectancyyears life expectancy
Who should be treated?Who should be treated?
Severe disease
AST>10foldsAST>5folds+
IGgx2Bridging necrosis orMultiacinar necrosis
•Mild disease•AST/G globulin
<absolute criteria•Interface hepatitis
•Mild disease•AST/G globulin
<absolute criteria•Interface hepatitis
Benefit-risk ratioundefined
Clinical judgment
Recommendation Recommendation
Severe diseaseSevere diseaseSymptomatic diseaseSymptomatic disease Interface hepatitis alone does not Interface hepatitis alone does not
compel treatmentcompel treatmentTreatment not indicated in patients Treatment not indicated in patients
with inactive cirrhosis, preexistent with inactive cirrhosis, preexistent comorbid conditionscomorbid conditions
Treatment in most childrenTreatment in most children
Regimens : prednisoneRegimens : prednisone
20mg
30mg
30mg
40mg
60mg
End point
Regimens : prednisoneRegimens : prednisone
20mg
30mg
30mg
40mg
60mg
End point
CytopeniaThiopurine methyl
transferase deficiencyMalignancy
RegimensRegimens
prednisone+azathioprine prednisone+azathioprine
10mg+50mg
15mg+50mg
15mg+50mg
20mg+50mg
30mg+50mg
End point
RegimensRegimens
prednisone+azathioprine prednisone+azathioprine
10mg+50mg
15mg+50mg
15mg+50mg
20mg+50mg
30mg+50mg
End point
PostmenopauseOsteoporosis
Brittle DMObesity
HypertensionEmotional lability
There is no prescribed minimum or There is no prescribed minimum or maximum duration of treatmentmaximum duration of treatment
Therapy should not be instituted with Therapy should not be instituted with the intention of being indefinitethe intention of being indefinite
Treatment End PointsTreatment End Points
Rx End Points
Remission Failure Incomplete response
Relapse
Pattern of responsePattern of response
Biochemical improvement
(90%)
Histologicimprovement
Remission1-2y
(80%)
Pattern of responsePattern of response
Biochemical improvement
(90%)
Histologicimprovement
Remission1-2y
(80%)
•No symptoms•Normal billirubin/glob
•AST<2UN•Normal tissue
•No interface hepatitis
Treatment failureTreatment failure(9%)(9%)
Worsening clinical,Laboratory& histologic
features
Increase AST>67%Development of jaundice
Ascites or encephalopathy
Incomplete responseIncomplete response(13%)(13%)
No or some improvement in Clinical, laboratory& Histologic feature
No remission after 3y
No worsening of condition
Relapse Relapse
Occurs in 20-100%Occurs in 20-100% Depends on histology at end pointDepends on histology at end point Liver biopsy prior to termination is preferred Liver biopsy prior to termination is preferred
but not essentialbut not essential Increase AST>3foldsIncrease AST>3folds Increase gamma globulin>2g/dlIncrease gamma globulin>2g/dl
Relapse Relapse
Depends on Depends on histology at end histology at end pointpoint
Relapse rate
Normal20%
Portal hepatitis50%
Interface hepatitisCirrhosis
100%
Management after relapseManagement after relapse
Indefinite low dose prednisoneIndefinite low dose prednisone Indefinite azathioprineIndefinite azathioprine
*87% remission*12% were able to be withdrawn from medication(6y)
Liver transplantationLiver transplantation
Indicated if deterioration occurs Indicated if deterioration occurs during or after corticosteroid during or after corticosteroid treatment (10%) treatment (10%)
5 year patient & graft survival 83-5 year patient & graft survival 83-92%92%
Auto antibodies disappear within 1yAuto antibodies disappear within 1yDisease recurrence is mild (10-35%)Disease recurrence is mild (10-35%)
