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1 Postgraduate Course 2011: The Liver and Other Organs .. Autoimmune liver diseases Sook-Hyang Jeong Department of Internal Medicine, Seoul National University Bundang Hospital, College of Medicine, Seoul National University, Korea Autoimmune liver disease is an undefined immune mediated attack to the hepatocyte, small intrahepatic bile ducts, and the entire biliary system leading to chronic inflammation and fibrosis. It includes autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), IgG4-associated cholangitis (IAC), and variant forms such as overlap syndrome.

2 PBC, PSC and IAC are cholestatic diseases showing different clinical features, diverse serological profiles, and different therapeutic regimens. AIH is characterized by circulating autoantibodies, elevated immunoglobulins, and dramatic response to immunosuppression. Despite of distinction of two main disorders, some patients showed an overlap disease with mixed features of both disorders. To prevent the progression to the end stage liver disease, early and precise diagnosis and initiation of therapeutic measures are essential. Liver transplantation is indicated for the treatment refractory advanced cirrhosis.

3 Further studies on the autoimmune liver diseases in Korea are warranted. Key words: Autoimmune diseases, Autoimmune hepatitis, Cholangitis, Biliary cirrhosis . 5% , . , . (autoimmune hepatitis, AIH), (primary biliary cirrhosis, PBC), (primary sclerosing cholangitis, PSC), 4 (IgG4-associated cholangitis, IAC) overlap syndrome AIH. , . AIH IAC prednisolone . azathioprine , PBC ursodeoxycholic acid (UDCA) PSC .. , . 15. Postgraduate Course 2011.. 1,2. 1. (AIH). 1) . , , T .. 10 15 .. Table 1. Revised Diagnostic Scoring System for Autoimmne Hepatitis (The International Autoimmune Hepatitis Group, 1999).

4 Com ponent Result Points Sex Fem ale 2. ALP:AST (or ALT) ratio >3 2. < 2. g-globulin or IgG level > 3. 2. 1. < 0. AN A, ASM or anti-LKM 1 titers > 1:80 3. 1:80 2. 1:40 1. < 1:40 0. AM A Positive 4. Viral m arkers of active infection Positive 3. N egative 3. Hepatotoxic drugs Yes 4. No 1. Alcohol < 25 g/day 2. > 60 g/day 2. Concurrent im m une disease Any nonhepatic disease of an im m une nature 2. O ther autoantibodies Anti-SLA, actin, LC1, pANCA 2. Histological features Interface hepatitis 3. Plasm a cells 1. Rosettes 1. N one of above 5. Biliary changes 3. O ther features 3.

5 HLA D R3 or DR4 1. Treatm ent response Rem ission alone 2. Rem ission with relapse 3. Pretreatm ent score D efinite diagnosis > 15. Probable diagnosis 10-15. Posttreatm ent score D efinite diagnosis > 17. Probable diagnosis 12-17. 16.. 2) . 1:3 , immunoglobulin .. 15 49% . , 6 40% . 3) . , (antinuclear antibodies, ANA), (anti-smooth muscle antibodies, ASM) anti-LKM1 , , , .. International autoimmune hepatitis group (IAIHG) . (1999 ) (Table 1) 2008 . (Table 2). 4) . 10 , 5 2 . , . prednisolone 30 mg azathioprine 50 mg prednisolone 60 mg 4 . prednisolone 10 mg + azathiprine 50 mg prednisolone 20 mg 2.

6 5) . 80% remission 20 80% .. 5 85%, AIH . Table 2. Sim plified Diagnostic Criteria for Autoim m une Hepatitis Variable Cutoff Points ANA or ASM 1:40 1. ANA or ASM 1:80. or LKM 1:40 2. or SLA Positive IgG U pper norm al lim it 1. > tim es norm al lim it 2. *. Liver histology Com patible with AIH 1. Typical AIH 2. Absence of viral hepatitis Yes 2. Definite autoim m une hepatitis (AIH ) 7. Probable AIH 6. adapted by Hennes EM et al. Hepatology 2008;48:169-176. 17. Postgraduate Course 2011. 68% .. 6) 3,4. 2004 172 AIH 48 , 1:9, 22%, 92%, 31% . remission 69% . 2010 86 AIH 51 , 1:5.

7 97% . 86% prednisolone+azathioprine . 84% remission 24 1 42% . 10 96% . 5-6. 2. (PBC). 1) . , PBC , , . 5 . 15% . 2) . 50 , 1:9 .. , , .. 3) . 3 2 . (1) ( , 2 ). (2) (antimitochondrial antibody, AMA) 1:40. (3) nonsuppurative destructive cholangitis, destruction of interlobular bile duct 4) . ursodeoxycholic acid (UDCA) 13-15 mg/kg/day . cholestyramine 4 g/dose 1 16 g UDCA 2-4 . Cholestyramine rifampicin 150-300 mg/day, naltrexone 50 mg/day, sertraline 75-100 mg/day .. calcium 1,000-1,500 mg/day, vitamin D 1,000 IU/day, alendronate 70 mg/week . UDCA glucocorticoid (prednisolone or budesonide) methotrexate UDCA ( ).

8 Farnesoid X receptor (FXR) agonist obeticholic acid, peroxisome proliferator activated receptor (PPAR ). agoinst bezafibrate, fenofibrate . 18.. 5) . UDCA 3-6 .. UDCA 10 84%, 20 66% . PBC . 5 . 80-85%, PBC 15% . 6) 7. 251 PBC 54 , 1:9, 61%, 12% , 98% . 88% . UDCA 5 95% , , , Mayo score . 5,8. 3. (PSC). 1) .. 2) . 2:1 40 , , , .. 80% PSC . 3) . ( ). , fibro-obliterative cholangitis PSC (small duct PSC). Perinuclear antineutrophil cytoplasmic antibodies (pANCA) 26-94% , ANA 8-77%, ASM 0-83% . 2 . , , , IgG4-associated cholangitis (IAC), AIDS cholangiopathy, ischemic cholangitis, cholangiocarcinoma.

9 4) . UDCA 15-20 mg/kg/day 28-30 mg/kg/day UDCA .. 5) . PSC . 1-2 . - (cholangiocarcinoma, gallbladder adenocarcinoma, 19. Postgraduate Course 2011. hepatocellular carcinoma) 1 .. 5 85% 5-10 20% PSC . 5,9. 4. Immunoglobulin G4-associated cholangitis (IAC). 1) . 60 PSC hilar cholangiocarcinoma . Glucocorticoid IgG4 associated autoimmune pancreatitis . 2) . 65 , 8:1 PSC .. 70% IgG4 prednisolone .. 3) . Biliary stricture (intrahepatic, proximal extrahepatic, intrapanctreatic bile ducts) . (1) autoimmune pancreatitis (AIP) IAC . (2) AIP IgG4 . (3) 4 2 , 4 steroid (stent.

10 , IgG4 CA19-9 steroid . ). ) IgG4 . ) suggestive pancreatic imaging ) other organ involvement (sclerosing sialadenitis, retroperitoneal fibrosis, GI involvement, abdominal lymphadenopathy with IgG4-positive plasma cells). ) > 10 IgG4-positive cells/HPF on biliary biopsy 4) . Prednisolone 30-40 mg/day 5 mg 3 .. 24-68% azathioprine (2 mg/kg/day) prednisolone .. 5) .. 5. Overlap syndrome10. 2 . 20.. 1) AIH/PBC overlap 10% AIH PBC PBC, AIH criteria 3 2 . PBC criteria: AP > 2 UNL or gGT > 5 UNL, AMA 1:40, compatible liver biopsy findings AIH criteria: ALT > 5 UNL, IgG > 2 UNL or ASM (+), compatible liver biopsy findings UDCA 13-15 mg/kg/day steroid/azathioprine.