原発性胆汁性肝硬変（PBC）の診療ガイドライン …

1 PBC (2012 ).. 2012 3 . Ver. 2011. 3. Ver. 2012. 3. Ver. 1.. Primary biliary cirrhosis: PBC . 1851 Addison & Gull 1950 Ahrens Primary biliary cirrhosis . chronic non-suppurative destructive cholangitis: CNSDC .. Anti-mitochondrial antibody: AMA . PBC . AMA .. ursodeoxycholic acid; UDCA 1980 . PBC UDCA . UDCA PBC PBC . 2009 PBC . AASLD, EASL .. PBC . 2011 3 .. MSD( ). ( ) ( ). ( ) MSD( ) . COI .. PBC WG .. WG .. 2.. PBC . PBC . PBC .. Q -1: (PBC) . Q -2: . Q -3: . Q -4: . Q -5: . Q -6: . Q -7: PBC . Q -8: . Q -9: . PBC . Q -1: PBC . Q -2: PBC . 3. PBC . UDCA. Q -1-1: UDCA . Q -1-2: UDCA.

2 Q -1-3: UDCA . Q -1-4: UDCA . Q -1-5: UDCA . Q -1-6: UDCA . Bezafibrate Q -2-1: Bezafibrate . Q -2-2: Bezafibrate .. Q -3-1: . Q -3-2: . Q -3-3: .. Q -1-1: Cholestyramine PBC . Q -1-2: PBC . Q -1-3: Rifampicin PBC .. Q -2-1: . Q -2-2: Bisphosphonate PBC . Q -2-3: vitaminD3 vitaminK2 PBC .. Q -3-1: cevimeline pilocarpine PBC . PBC .. Q -1-1: . Q -1-2: . Q -1-3: . Q -1-4: PBC . Q -1-5: . Q -1-6: .. Q -2-1: . Q -2-2: . 4.. Q -1-1: . Q -1-2: . Q -1-3: PBC . Q -1-4: .. Q -2-1: . Q -2-2: . Q -2-3: PBC . Q -2-4: PBC . 5.. PBC . PBC . PubMed-MEDLINE . Clinical Trial, RCT, Meta-Analysis 01/1998 12/2009 Primary biliary cirrhosis.

3 English UDCA . 1b UDCA . 1987 Poupon Lancet .. UDCA. PBC PBC 2009 . PBC AASLD, . EASL . Impact Factor .. , .. Minds( ) .. 1a . 1b . 2a . 2b . 3 . 4 . 5 . 6 .. A . B . C1 . C2 . D . 6.. 22 .. primary biliary cirrhosis PBC .. (symptomatic)PBC(sPBC) asymptomatic . PBC (aPBC) . sPBC aPBC . sPBC mg/dl . s2 PBC s1 PBC . 1.. ALP GTP . antimitochondrial antibodies AMA 90% IgM .. 2.. chronic non-suppurative destructive cholangitis CNSDC .. 3.. 4.. PBC . 1 CNSDC PBC . 2 AMA CNSDC PBC compatible .. 3 AMA PBC .. 7. PBC .. 1 PBC . ALP, -GTP . AMA ELISA . CNSDC . 22 . A . 1 . 1) CNSDC PBC . 2) AMA CNSDC PBC compatible.

4 2 . 3) AMA PBC .. MEMO ELISA . AMA PBC 90% .. ELISA AMA . M2 PBC M2 . 70kDa, 50kDa, 47kDa, 40kDa . 70kDa M2 . PDC: pyruvate dehydrogenase complex E2 component (PDC-E2) . 2-acid dehydrogenase complex . (BCOADC-E2) OGDCE) PBC M2 .. ELISA 3 . ELISA . (Gershwin ME, et al. Molecular biology of the 2-oxo-acid dehydrogenase complexes and anti-mitochondrial antibodies. Prog Liver Dis 10:47-61, 1992.).. 2 .. CT . A . 2 PBC . 1 . IgG4 .. 2 . 3) ALP, -GTP . 8.. PBC .. 1 PBC early PBC . AMA . PBC . 2) Autoimmune cholangitis, Autoimmune cholangiopathy: AIC . PBC AMA ANA 1987. Brunner & Klinge Immunocholangitis.

5 Autoimmune cholangiopathy primary autoimmune cholangitis autoimmune cholangitis PBC UDCA .. 3) AMA PBC. AMA PBC . PBC PBC 10% AMA AMA . T PBC .. 4 PBC-AIH . PBC ALT . ALT PBC PBC .. (7 8 . PBC PBC 1) . 2) 3) . 3 .. PBC .. PBC .. 3. PBC . PBC . 1) 1) . 2) . 3) . 2) .. 4) .. 3) . 5) .. 9.. 1) PBC . PBC .. PBC .. PBC . (chronic non-suppurative destructive cholangitis; CNSDC) .. PBC . CNSDC . CNSDC . CNSDC .. PBC .. cholate stasis .. zone 1 small cell dysplasia PBC . PBC .. 2 . PBC Nakanuma . PBC . Scheuer Ludwig .. 2009 4,5,6 . 4 PBC . Stage 1 S no progression . Stage 2 S mild progression.

6 Stage 3 S moderate progression . Stage 4 S advanced progression .. 10. 5 PBC , 2006, , 2010 . 5-1 PBC . A. Score B. Score . 0 0.. 1 1/3 1.. 2 1/3-2/3 2. 3 2/3 3. 5-2 (A) (B) (Staging). A. B.. Stage . Stage 1 (no progression) 0. Stage 2 (mild progression) 1-2. Stage 3 (moderate progression) 3-4. Stage 4 (advanced progression) 5-6. C.. 5-3 (Staging). C. Score 0. 1/3 . 1.. 1/3-2/3 ( . 2. ) . 2/3 . 3.. A. B.. Stage C.. Stage 1 (no progression) 0. Stage 2 (mild progression) 1-3. Stage 3 (moderate progression) 4-6. Stage 4 (advanced progression) 7-9. 11. 6 PBC . 6-1 Cholangitis activities (CA).

7 CA0 (no activity). CA1 (mild activity). 2 CA2 (moderate activity). CNSDC CA3 (marked activity). 6-2 Hepatitis activities (HA). HA0 (no activity). 1/3 HA1 (mild activity). 10 . 2/3 HA2 (moderate activity). 10 . HA3 (marked activity).. (Hiramatsu K, Aoyama H, Zen Y, et al. Proposal of a new staging and grading system of the liver for primary biliary cirrhosis. Histopathology. 2006;49:466-78.). (Nakanuma Y, Zen Y, Harada K, et al. Application of a new histological staging and grading system for primary biliary cirrhosis to liver biopsy specimens: Interobserver agreement. Pathol Int 2010 Mar;60(3):167-74.)

8 12. MEMO PBC . PBC . 1) Scheuer PBC . CNSDC . 2) Ludwig . Portal hepatitis (Periportal hepatitis) . Septal (Bridging) fibrosis), (Cirrhosis) . 3) Nakanuma PBC .. PBC . Scheuer Scheuer PJ , 1967 . Florid bile . duct lesion .. florid bile duct lesion . Ductular . proliferatio n Scarring, piecemeal necrosis . septal . fibrosis and bridging Cirrhosis . Scheuer PJ: Primary biliary cirrhosis. Proc R Soc Med, 1967; 60; 1257-1260. Scheuer PJ. Pathologic features and evolution of primary biliary cirrhosis and primary sclerosing cholangitis. Mayo Clin Proc. 1998;73:179-83.. Ludwig Ludwig et al, 1978.

9 Portal . hepatitis . florid duct lesion .. Periportal . hepatitis .. Septal Stage 2 . (bridging) . fibrosis . Cirrhosis garland-shaped regenerative nodules . ductopenia .. Ludwig J, Dickson ER, McDonald GS. Staging of chronic nonsuppurative destructive cholangitis (syndrome of primary biliary cirrhosis. Virchows Arch A Pathol Anat Histol. 1978 22;379(2):103-12). 13.. 1 . PBC PBC aPBC PBC sPBC . sPBC s1 PBC . s2 PBC 7 . 7 PBC . PBC aPBC : . PBC sPBC : . s1 PBC . s2 PBC .. aPBC ( ) sPBC s1 PBC ( ) s2 PBC ( . ) . 2) . 2 .. PBC . PBC Bil PBC . Child-Pugh 8 .. 8 PBC . 1 PBC aPBC . 2 PBC sPBC PBC Child-Pugh.

10 PBC Child-Pugh . Score 1 2 3. Bil (mg/dl) 1 4 4 10 >10. Alb (g/dl) < < PT (%) 70%< 40 70% <40%. INR < > . Grade1 2 Grade 3 4. Grade A: 5 6 Grade B: 7 9 Grade C: 10 15 .. PBC . 9 PBC . 1) . 2) . 3) . 1 PBC . 14. PBC 9, 1 .. MEMO gp210 PBC . PBC gp210. multiple nuclear dot sp100 . 20 30% PBC .. gp210 gp210 PBC. 20 30% 100% gp210 PBC. gp210 . interface hepatitis . UDCA gp210 .. (Nakamura M, Shimizu-Yoshida Y, Takii Y, et al. Antibody titer to gp210-C terminal peptide as a clinical parameter for monitoring primary biliary cirrhosis. J Hepatol 42:386-392, 200 . Nakamura M, Kondo H, Mori T, et al.