Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis.
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.
Nakamura
Minoru
M
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
Kondo
Hisayoshi
H
Mori
Tsuyoshi
T
Komori
Atsumasa
A
Matsuyama
Mutsumi
M
Ito
Masahiro
M
Takii
Yasushi
Y
Koyabu
Makiko
M
Yokoyama
Terufumi
T
Migita
Kiyoshi
K
Daikoku
Manabu
M
Abiru
Seigo
S
Yatsuhashi
Hiroshi
H
Takezaki
Eiichi
E
Masaki
Naohiko
N
Sugi
Kazuhiro
K
Honda
Koichi
K
Adachi
Hiroshi
H
Nishi
Hidehiro
H
Watanabe
Yukio
Y
Nakamura
Yoko
Y
Shimada
Masaaki
M
Komatsu
Tatsuji
T
Saito
Akira
A
Saoshiro
Takeo
T
Harada
Hideharu
H
Sodeyama
Takeshi
T
Hayashi
Shigeki
S
Masumoto
Akihide
A
Sando
Takehiro
T
Yamamoto
Tetsuo
T
Sakai
Hironori
H
Kobayashi
Masakazu
M
Muro
Toyokichi
T
Koga
Michiaki
M
Shums
Zakera
Z
Norman
Gary L
GL
Ishibashi
Hiromi
H
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
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