title: Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis.
abstract: The predictive role of antinuclear antibodies (ANAs) remains elusive in the long-term outcome of primary biliary cirrhosis (PBC). The progression of PBC was evaluated in association with ANAs using stepwise Cox proportional hazard regression and an unconditional stepwise logistic regression model based on the data of 276 biopsy-proven, definite PBC patients who have been registered to the National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ). When death of hepatic failure/liver transplantation (LT) was defined as an end-point, positive anti-gp210 antibodies (Hazard ratio (HR) = 6.742, 95% confidence interval (CI): 2.408, 18.877), the late stage (Scheuer's stage 3, 4) (HR = 4.285, 95% CI:1.682,10.913) and male sex (HR = 3.266, 95% CI: 1.321,8.075) were significant risk factors at the time of initial liver biopsy. When clinical progression to death of hepatic failure/LT (i.e., hepatic failure type progression) or to the development of esophageal varices or hepatocellular carcinoma without developing jaundice (Total bilirubin < 1.5 mg/dL) (i.e., portal hypertension type progression) was defined as an end-point in the early stage (Scheuer's stage 1, 2) PBC patients, positive anti-gp210 antibodies was a significant risk factor for hepatic failure type progression [odds ratio (OR) = 33.777, 95% CI: 5.930, 636.745], whereas positive anti-centromere antibodies was a significant risk factor for portal hypertension type progression (OR = 4.202, 95% CI: 1.307, 14.763). Histologically, positive anti-gp210 antibodies was most significantly associated with more severe interface hepatitis and lobular inflammation, whereas positive anticentromere antibodies was most significantly associated with more severe ductular reaction.
  
  
  CONCLUSIONS
  These results indicate 2 different progression types in PBC, hepatic failure type and portal hypertension type progression, which may be represented by positive-anti-gp210 and positive-anticentromere antibodies, respectively.
authors.affiliation: Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center and Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Nagasaki, Japan. nakamuram@nmc.hosp.go.jp
authors.forename: Minoru
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Kondo
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Mori
authors.forename: Atsumasa
authors.initials: A
authors.lastname: Komori
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Matsuyama
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ito
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takii
authors.forename: Makiko
authors.initials: M
authors.lastname: Koyabu
authors.forename: Terufumi
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Migita
authors.forename: Manabu
authors.initials: M
authors.lastname: Daikoku
authors.forename: Seigo
authors.initials: S
authors.lastname: Abiru
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yatsuhashi
authors.forename: Eiichi
authors.initials: E
authors.lastname: Takezaki
authors.forename: Naohiko
authors.initials: N
authors.lastname: Masaki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sugi
authors.forename: Koichi
authors.initials: K
authors.lastname: Honda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Adachi
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Nishi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Masaaki
authors.initials: M
authors.lastname: Shimada
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Komatsu
authors.forename: Akira
authors.initials: A
authors.lastname: Saito
authors.forename: Takeo
authors.initials: T
authors.lastname: Saoshiro
authors.forename: Hideharu
authors.initials: H
authors.lastname: Harada
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sodeyama
authors.forename: Shigeki
authors.initials: S
authors.lastname: Hayashi
authors.forename: Akihide
authors.initials: A
authors.lastname: Masumoto
authors.forename: Takehiro
authors.initials: T
authors.lastname: Sando
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Hironori
authors.initials: H
authors.lastname: Sakai
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Toyokichi
authors.initials: T
authors.lastname: Muro
authors.forename: Michiaki
authors.initials: M
authors.lastname: Koga
authors.forename: Zakera
authors.initials: Z
authors.lastname: Shums
authors.forename: Gary L
authors.initials: GL
authors.lastname: Norman
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ishibashi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000974:Antibodies, Antinuclear / Q000097:blood* / Q000276:immunology; D034961:Antigens, Nuclear / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D002503:Centromere / Q000276:immunology*; D002843:Chromatin / Q000276:immunology; D018450:Disease Progression; D004932:Esophageal and Gastric Varices / Q000209:etiology; D005260:Female; D006801:Humans; D006975:Hypertension, Portal / Q000209:etiology; D008105:Liver Cirrhosis, Biliary / Q000145:classification* / Q000150:complications / Q000276:immunology*; D017093:Liver Failure / Q000209:etiology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D028861:Nuclear Pore Complex Proteins / Q000276:immunology*; D009687:Nuclear Proteins / Q000276:immunology; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000974:Antibodies, Antinuclear; D034961:Antigens, Nuclear; D001324:Autoantigens; D002843:Chromatin; C063865:NUP210 protein, human; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; C066642:SP100 protein, human