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1 7 Recent Diagnosis and Treatment of Autoimmune HepatitisYoung Seok Kim, of Internal Medicine, Soon Chun Hyang University, Seoul, Korea Autoimmune hepatitis (AIH) is a chronic hepatitis of unknown etiology which can progress to cirrhosis, and charac-terized by histological interface hepatitis, hypergammaglobulinemia, and circulating autoantibodies. There are no pathog-nomic findings of AIH. The diagnosis of autoimmune hepatitis is usually made using descriptive criteria. The sensitivity and specificity of the codified diagnostic criteria of AIH proposed by International Autoimmune Hepatitis Group are over 90%, respectively.

2 Its clinical manifestations are highly variable and sometimes follow a fluctuating course. Immunosup-pressive therapies with prednisone and azathioprine frequently induce remission but relapses occur in more than 80% of patients within 1 year after drug withdrawal. Alternative immunosuppressive drugs may be tested in patients with suboptimal responses to conventional drugs. Liver transplantation remains the only treatment option for the end stage of liver disease. In the future, alternative approaches in modulating the immune system may become words: Autoimmune hepatitis; Diagnosis; Treatment; Prognosis (autoimmune hepatitis, AIH) (interface hep-atitis), (plasma cell).

3 1 B 70%, C 10~20% , , , . ,2 ,3 8 10,000 ~ .4,5 (85% 38%),6 ,7 2004 .8 HLA HLA-DR3 HLD-DR4 9 HLA-DRB1*0405 1 .10 40% ,11.

4 12 1/3 ,13 ALT .. ,14 . 6 40% ,15 40% ,16 2 54% 20% .17 , 15 49% 10% ,18 6 .15 30% ,19 , ,20 .21 ,22 TH1 TH2 .23 1 2 ( 1) (antinuclear an-tibody, ANA) (smooth-muscle antibody, SMA) 1.

5 , , , (pri-mary biliary cirrhosis, PBC) (primary sclerosing cholangitis, PSC) .24,25 International Autoimmune Hepatitis Group (IAIHG) 26 homogenous speckled ,27 ..28 (33%), (54%).29 1 3/4 10~20 , 45~75 .30 25% , 40% , , . 2 1 (antibody against liver-kidney microsome 1, an-ti-LKM1) CYP2D6 .31 2 2~14 90% 1.

6 32 4% anti-LKM1 anti-LKM1 20% ,33 CYP2D6 C C an- 9 Table 1. Classification of autoimmune hepatitisVariableType 1 AIHType 2 AIHC haracteristic autoantibodiesANA, SMA, Antiactin antibody. Anti-SLA/LP, Atypical pANCAAnti-LKM1, Anti-LC1 AutoantigenUnknownCYD2D6 Geographic variationWorldwideWorldwide; rare in North AmericaAge at presentationAny agePredominantly childhood and young adulthoodSex of patientsFemale (75%)Female (95%)Acute or fulminant onsetYesYesAssociation with other autoimmune diseases 38%34%Typical concurrent immune diseaseThyroiditisGrave's diseaseUlcerative colitisThyroiditisVitiligoType 1 diabetesAPECEDA ssociated HLAB8, DR3, DR4B14, DR3, CA4-Q0, DR7 Clinical severityBroad rangeGenerally severeHistopathologic features at presentationBroad rangeGenerally advancedSteroid responsive+++++Treatment failureInfrequentFrequentRelapse after drug withdrawalVariableCommonNeed for long-term maintenanceVariableApproximately 100%McFarlane IG.

7 Clin Liver Dis 2002; 6:605-621 Krawitt EL. N Engl J Med 2006;354:54-99ti-LKM1 .34 ( 2) pANCA(perinuclear anti-neutrophil cytoplasmic antibodies), anti-LC1(liver specific cytosol antigen type 1), anti-ASGPR(antibodies to asialoglycoprotein receptor), IgA endomysial antibodies, anti-SLA/LP(antibodies to soluble liver antigen)/liver pancreas), anti-ac-tin .24 anti SLA 3 ,35 pANCA 1 .24 ,36 ,29.

8 37 , , (IgM anti-HAV, HBsAg, IgM an-ti-HBc, anti-HCV, HCV-RNA) . , AST, ALT 10 Table 2. Molecular definitions of autoantigens relevant to the serological diagnosis of autoimmune hepatitisAntibody Target antigen in AIHL iver diseaseAssociated with in AIHANA Centromere, Ribonucleoproteins AIH, PBC, PSC, Drug-induced hepatitis, HCV, HBV, NASHSMA Actin, Tubulin, vimentin, desmin, skeleton Same as ANA HLA A1-B8-DR3, younger patients, poorer PxpANCA Unknown AIH, PSCLKM-1 Cytochrome P450 2D6 AIH-2, HCVLKM-2 Cytochrome P450 2C9 Ticrynafen-induced hepatitisLKM-3 UGT1A HDV, AIH-2, APECED, HCVLM Cytochrome P450 1A2 Dihydralazine-induced hepatitis, APECED, HCVC ytochrome P450 2A6 APECEDLC-1 Formiminotransferase cyclo-deaminase AIH-2, HCV Disease activity.

9 Younger patientsSLA/LP UGA repressor tRNA-associated proteinAIH, HCV More severe course, relapse after drug withdrawalASGPR Asialoglycoprotein receptor AIH, PBC, Drug-induced hepatitis, HCV, HBV, HDVD isease activityChromatin Chromatin Disease activity, relapse after drug withdrawalCLAC ardiolipinAIH, HCV, HBV Disease activityASCA Saccharomyces cerevisiae AIH, PSC, PBCM anns MP et al Hepatology 2006;43:S132-144 , , (minocycline, nitrofurantoin, isoniazid, propylth-iouracil -methyldopa ), , , , .. , IgG , , anti-LKM1 . , (panacinar hepatitis).

10 38 , . , , .AASLD , , anti-LKM1 ( 3) .281993 IAIHG (minimum required parameter) (additional parameter) . C ALP/AST 11 Table 3. Diagnostic criteria for autoimmune hepatitisDiagnostic CriteriaDefiniteProbableNo genetic liver diseaseNormal 1 antitrypsin phenotypePartial 1 antitrypsin deficiencyNormal serum ceruloplasmin, iron, and ferritin levelsNonspecific serum copper, ceruloplasmin, iron, and/or ferritin abnormalitiesNo active viral infectionNo markers of current infection with hepatitis A, B, and C virusesNo markers of current infection with hepatitis A, B.