| Co-Investigator(Kenkyū-buntansha) |
KOMORI Atsumasa Nagasaki Medical Center, Clinical Research Center, Division Chief of Regererative medicine, 臨床研究センター・再生医療研究部, 室長 (50234901)
MIGITA Kiyoshi Nagasaki Medical Center, Clinical Research Center, Director of the Department of Pathogenesis Research, 臨床研究センター・病因解析研究部, 部長 (60264214)
YATSUHASHI Hiroshi Nagasaki Medical Center, Clinical Research Center, Director of the Department of Therapeutic Research, 臨床研究センター・治療研究部, 部長 (50360855)
ISHIBASHI Hiromi Nagasaki Medical Center, Clinical Research Center, Director General, 臨床研究センター, 臨床研究センター長 (80127969)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
The predictive role of anti-nuclear antibodies (ANAs) remains elusive in the long-term outcome of primary biliary cirrhosis (PBC). The aim of this study is to clarify the significance of ANAs in the progression of PBC.The associations between ANAs and the progression of PBC were evaluated using step-wise Cox proportional hazard regression and an unconditional step-wise logistic regression model based on the data of 276 biopsy-proven, definite PBC patients who have been registered to National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ). Serum antibodies to nuclear antigens including gp210, centromere, sp100 and chromatin were measured by ELISA over periods extending from 1 to 292 (median 60.5) months of observation. A total of 91 PBC liver biopsy specimens were also assessed for histological variables in relation to ANAs.When death of hepatic failure/liver transplantation (LT) was defined as an end-point in all PBC patients, positive anti-gp210 antibodies (Haza
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rd 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 hepatocelluar carcinoma without developing jaundice (T.bilirubin<1.5mg/dl) (i.e. non-hepatic failure 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 non-hepatic failure 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, while positive anti-centromere antibodies was most significantly associated with more severe ductular reaction These results indicate that there are two different progression-types in PBC, hepatic failure type-and non-hepatic failure type-progression, which may be represented by positive-anti-gp210 and-anti-centromere antibodies, respectively. Less
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