title: Aberrant Expression of Keratin 7 in Hepatocytes as a Predictive Marker of Rapid Progression to Hepatic Failure in Asymptomatic Primary Biliary Cirrhosis.
abstract: A predictive marker of the rapid progression to hepatic failure is desired for patients with asymptomatic primary biliary cirrhosis (aPBC). We performed a systematic cohort analysis of 101 patients diagnosed as having aPBC and the rapid progression to liver failure in some, by focusing on cholestasis. Cholestasis was assessed by aberrant keratin7 (K-7) expressions in the patients' hepatocytes. Intralobular expressions of K-7 were found in 9 of the 101 patients. The grades of K-7 expression were significantly associated with the levels of alanine aminotransferase, alkaline phosphatase, and total bilirubin at the time of diagnosis, but not with bile duct loss or cholestasis. Stepwise logistic regression analysis revealed that high grades of K-7 expression correlated positively with high levels of total bilirubin. During the follow-up period, 8 patients developed jaundice, and the mean period until the development of jaundice was 5.2 years. The proportional hazards models for the risk of developing jaundice identified a high grade of aberrant K-7 expression in hepatocytes as the only significant risk factor. Aberrant K-7 expression in hepatocytes can be used as an additional marker to predict rapid progression to liver failure in patients with aPBC at the time of diagnosis.
authors.affiliation: Department of aGastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Seki
authors.forename: Fusao
authors.initials: F
authors.lastname: Ikeda
authors.forename: Shintaro
authors.initials: S
authors.lastname: Nanba
authors.forename: Yuki
authors.initials: Y
authors.lastname: Moritou
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yasunaka
authors.forename: Hideki
authors.initials: H
authors.lastname: Onishi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miyake
authors.forename: Akinobu
authors.initials: A
authors.lastname: Takaki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nouso
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Iwasaki
authors.forename: Minoru
authors.initials: M
authors.lastname: Nakamura
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D018450:Disease Progression; D005260:Female; D022781:Hepatocytes / Q000737:chemistry*; D006801:Humans; D053552:Keratin-7 / Q000032:analysis*; D008105:Liver Cirrhosis, Biliary / Q000150:complications / Q000378:metabolism*; D017093:Liver Failure / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers; C507497:KRT7 protein, human; D053552:Keratin-7