Autoimmune Hepatitis/ Autoimmune Pancreatitis EdmundEdmund Krasinski,Krasinski, JrJr.,., D.O.D.O. F.A.C.G.F.A.C.G. Assessment of Liver Function WhichWhich ofof thethe followingfollowing isis notnot aa goodgood biochemicalbiochemical assessorassessor ofof hepatichepatic function?function? A)A) SerumSerum bilirubinbilirubin B)B) SerumSerum lactatelactate dehydrogenasedehydrogenase C)C) SerumSerum aspartateaspartate aminotransferaseaminotransferase (AST)(AST) D)D) SerumSerum alaninealanine aminotransferaseaminotransferase (ALT)(ALT) E)E) SerumSerum alkalinealkaline phosphatasephosphatase Assessment of Liver Function CorrectCorrect answeranswer :: BB MeasurementMeasurement ofof LDHLDH andand eveneven moremore specificspecific LDHLDH--55 addsadds littlelittle toto evaluationevaluation ofof suspectedsuspected hepatichepatic dysfunctiondysfunction HighHigh levelslevels ofof LDHLDH seenseen in:in: HepatocellularHepatocellular necrosis,necrosis, IschemicIschemic hepatopathyhepatopathy ““shockshock liverliver””,, Cancer,Cancer, HemolysisHemolysis Case Presentation AA 3535 yr.yr. OldOld femalefemale presentspresents forfor evaluation.evaluation. SheShe hashas notednoted jaundicejaundice manifestmanifest byby scleralscleral icterusicterus,, acholicacholic stools,stools,choluriacholuria.. SheShe alsoalso complainscomplains ofof undueundue fatigue.fatigue. SheShe tooktook aa recentrecent triptrip toto NewNew OrleansOrleans wherewhere sheshe ateate rawraw oysters.oysters. Case Presentation Meds:Meds: MacrodantinMacrodantin PhysicalPhysical examination:examination: GeneralizedGeneralized icterusicterus,,ScleralScleral icterusicterus,, TenderTender hepatomegalyhepatomegaly,, NoNo stigmatastigmata ofof chronicchronic liverliver diseasedisease Case presentation Labs:Labs: SerumSerum bilirubinbilirubin 15.015.0 SerumSerum ASTAST 15001500 SerumSerum ALTALT 17001700 SerumSerum AlkAlk phosphos 120120 Case Presentation WhichWhich ofof thethe followingfollowing diseasesdiseases areare consistentconsistent withwith thisthis clinicalclinical presentation?presentation? A)A) AutoimmuneAutoimmune hepatitishepatitis B)B) ViralViral hepatitishepatitis C)C) WilsonWilson’’ss DiseaseDisease D)D) DrugDrug--inducedinduced liverliver diseasedisease E)E) AllAll ofof thethe aboveabove Case Presentation CorrectCorrect answer:answer: E)E) AllAll ofof thethe above.above. AllAll ofof thethe diseasesdiseases inin thethe differentialdifferential diagnosisdiagnosis cancan presentpresent asas such.such. AllAll cancan presentpresent withwith acuteacute decompensationdecompensation withwith primarilyprimarily hepatocellularhepatocellular dysdysfunctionfunction Case Presentation AutoimmuneAutoimmune hepatitishepatitis-- ToTo bebe discusseddiscussed atat length.length. ViralViral hepatitis:hepatitis: HBsAgHBsAg,Anti,Anti--HBC,HBC,IgMIgM antianti-- HAV,HAV, AntiAnti--HCV.HCV. WilsonWilson’’ss Disease:Disease: SerumSerum ceruloplasminceruloplasmin,, 2424 hrhr urinaryurinary copper,copper, OpthoOptho evaleval forfor KayserKayser-- FleisherFleisher ringsrings DrugDrug inducedinduced liverliver dzdz..-- historyhistory ofof drugdrug POPO Autoimmune Hepatitis Definition:Definition: AA selfself--perpetuatingperpetuating hepatichepatic inflammationinflammation ofof unknownunknown cause,cause, characterizedcharacterized byby interfaceinterface hepatitis,hepatitis, hypergammaglobulinemiahypergammaglobulinemia,and,and liverliver associatedassociated antibodies.antibodies. Exclusion of other conditions WilsonWilson’’ss diseasedisease ChronicChronic viralviral hepatitishepatitis AlphaAlpha 11 antitrypsinantitrypsin deficiencydeficiency HereditaryHereditary hemochromotosishemochromotosis DrugDrug inducedinduced liverliver diseasedisease NonNon--alcoholicalcoholic steatohepatitissteatohepatitis ImmuneImmune cholangiopathiescholangiopathies:: PBC/PSCPBC/PSC Autoimmune Hepatitis Nomenclature:Nomenclature: AIHAIH replacesreplaces termsterms ofof lupoidlupoid hepatitis,hepatitis, autoimmuneautoimmune liverliver disease,disease, andand autoimmuneautoimmune chronicchronic activeactive hepatitis.hepatitis. Autoimmune Hepatitis NoNo subtypessubtypes formallyformally recognized,recognized, butbut descriptivedescriptive terms:terms: TypeType 11 TypeType 22 TypeType 33 Basic Diagnostic Tests AST,AST, ALT,ALT, BilirubinBilirubin,, alkalk phosphos,, gammagamma globulinglobulin levelslevels (( AssessAssess severityseverity ofof liverliver injuryinjury andand characterizecharacterize thethe patternpattern ofof injury)injury) SerumSerum albumin,albumin, PT/INRPT/INR (( EstimateEstimate levellevel ofof impairmentimpairment ofof hepatichepatic syntheticsynthetic function)function) ANAANA (( AntinuclearAntinuclear antibody)antibody) ASMAASMA (( AntiAnti-- smoothsmooth musclemuscle antibody)antibody) AntiAnti-- LKMLKM 11 (Anti(Anti--liverliver kidneykidney microsomalmicrosomal antibodyantibody SLASLA (( SolubleSoluble liverliver antigen)antigen) Autoimmune Hepatitis LiverLiver tissuetissue examinationexamination HistologicHistologic changeschanges confirmconfirm diagnosisdiagnosis InterfaceInterface hepatitishepatitis LobularLobular panacinarpanacinar hepatitishepatitis withwith interfaceinterface hepatitishepatitis Autoimmune Hepatitis ViralViral hepatitishepatitis exclusion:exclusion: HBsAgHBsAg// AntiAnti-- HBcHBc//IgMIgM AntiAnti--HAV/HAV/ AntiAnti--HCVHCV WilsonWilson’’ss diseasedisease exclusion:exclusion: SerumSerum ceruloplasminceruloplasmin HHCHHC exclusion:exclusion: SerumSerum Fe,Fe, TIBC/TIBC/ %% sat/sat/ FerritinFerritin// HFEHFE analysis(ifanalysis(if needed)needed) International Criteria for Diagnosis DiagnosticDiagnostic FeaturesFeatures DefinitiveDefinitive DiagnosisDiagnosis ExclusionExclusion ofof riskrisk DailyDaily ETOHETOH << 2525 factorsfactors forfor otherother gm/dgm/d diseasesdiseases NoNo hepatotoxichepatotoxic drugsdrugs NN AlphaAlpha 11 ATAT phenotypephenotype NormalNormal ceruloplasminceruloplasmin NormalNormal Fe/Fe/ ferritinferritin NoNo HAV/HBV/HCVHAV/HBV/HCV International Criteria for Diagnosis DiagnosticDiagnostic FeaturesFeatures Probable Diagnosis Daily ETOH < 50 gm/ d ExclusionExclusion ofof riskrisk No Hepatotoxic drugs factorsfactors forfor otherother Partial A1 AT deficiency diseasesdiseases Abnormal cu/ ceruloplasmin but Wilson’s excluded Non-specific Fe/ Ferritin abnls No HAV/HBV/HCV International Criteria for Diagnosis Diagnostic Features Definitive Diagnosis Probable Diagnosis Inflammatory Indices Serum AST/ALT elev Serum AST/ALT elev Min chol. chng Min Chol. Chng Auotantibodies ANA/ASMA/ALKM ANA/ASMA/ALKM ≥ 1: 80 (adults) ≥ 1: 40 ≥ 1: 20 (peds) Immunoglobulins Glob, IgG ≥1.5 N Inc. IgG any degree Histologic features Interface hep. Mod- Same severe, no bile lesions, gran., other dz ∆ International Scoring System for Diagnosis Factor Score + AMA -4 Viral Markers + -3 - +3 Hepatotoxic drugs Yes -4 No +1 Pretreatment score > 15 Definite diagnosis 10-15 Probable Diagnosis International Scoring System for Diagnosis Factors Score ETOH < 25 gm +2 ETOH > 60 gm -2 HLA DR3 or DR4 +1 Concurrent AI Dz +2 Other liver Ab +2 Interface Hepatitis +3 Plasmacytic inflitrate +1 Rosettes +1 No Charact. Features -5 Biliary changes -3 Fat/ granulomas -3 International Scoring System for Diagnosis FactorsFactors ScoreScore TreatmentTreatment responseresponse +2+2 completecomplete RelapseRelapse +3+3 PostPost treatmenttreatment scorescore DefiniteDefinite DiagnosisDiagnosis >17>17 ProbableProbable diagnosisdiagnosis 1212--1717 Pathogenesis PrincipalPrincipal HypothesisHypothesis AutoantigenAutoantigen DrivenDriven cellcell--mediatedmediated AutoantibodyAutoantibody DependentDependent cellcell-- mediatedmediated cytotoxicitycytotoxicity Subclassifications TypeType 11-- ++ ANA/ASMAANA/ASMA MostMost commoncommon USAUSA FemaleFemale gendergender 78%78% ConcurrentConcurrent autoimmuneautoimmune diseasesdiseases 38%38% AutoimmuneAutoimmune thyroiditisthyroiditis 12%12% GravesGraves diseasedisease 6%6% UlcerativeUlcerative colitiscolitis 6%6% RheumatoidRheumatoid arthritisarthritis 11 %% PerniciousPernicious anemiaanemia 1%1% PSSPSS 1%1% Subclassifications TypeType 11 CoombCoomb’’ss positivepositive hemolytichemolytic anemiaanemia 1%1% ITPITP 1%1% LeucocytoclasticLeucocytoclastic vasculitisvasculitis 1%1% NephritisNephritis 1%1% ErythemaErythema nodosumnodosum 1%1% PyodermaPyoderma gangrenosagangrenosa (( II havehave seenseen oneone case)case) FibrosingFibrosing alveolitisalveolitis 1%1% Subclassifications TypeType 11 HLAHLA DR3DR3 andand DR4DR4 areare independentindependent riskrisk factorsfactors forfor susceptibilitysusceptibility andand suggestssuggests aa polygenicpolygenic disorder.disorder. Subclassifications TypeType 22 ++ AntiAnti LKMLKM antibodyantibody AffectsAffects mainlymainly childrenchildren (2(2--1414 yrs)yrs) AffectsAffects 20%20% EuropeanEuropean adultsadults AffectsAffects 44 %% USAUSA patientspatients CommonlyCommonly associatedassociated with:with: VitiligoVitiligo DMDM--11 AutoimmuneAutoimmune thyroiditisthyroiditis Subclassifications TypeType 33 ++ SolubleSoluble liverliver antigenantigen (SLA)(SLA) Newest,Newest, LeastLeast establishedestablished MaybeMaybe aa variantvariant ofof typetype 11 Variants OverlapOverlap withwith PBCPBC ++ AMAAMA ++ bilebile ductduct injuryinjury onon histologyhistology ++ responseresponse toto steroidssteroids ifif alkalk phosphos ≤≤ 22 XX NormalNormal Variants OverlapOverlap withwith