title: Increased serum mitochondrial creatine kinase activity as a risk for hepatocarcinogenesis in chronic hepatitis C patients.
abstract: Serum mitochondrial creatine kinase (MtCK) activity was reportedly increased in cirrhotic patients although less prominent than that in hepatocellular carcinoma (HCC) patients. To elucidate the clinical significance of serum MtCK activity in chronic liver disease, 171 chronic hepatitis C patients were enrolled. Serum MtCK activity in study subjects was correlated with serum albumin, platelet counts, liver stiffness values and serum aspartate and alanine aminotransferase. In mouse fibrotic liver induced by bile duct ligation, ubiquitous MtCK mRNA and protein expressions were significantly enhanced and its immunoreactivity was increased, predominantly in hepatocytes. During the mean follow-up period of 2.7 years, HCC developed in 21 patients, in whom serum MtCK activity was significantly higher than that in patients without HCC development. Multivariate Cox regression analysis revealed that higher serum MtCK activity was a risk for HCC development. A cutoff value of MtCK for the prediction of HCC development was determined as 9.0 U/L on receiver operating characteristics analysis, where area under receiver operating characteristics curve was 0.754, with a sensitivity of 61.9%, a specificity of 92.8% and a high negative predictive value of 94.2%. Cumulative incidence of HCC was significantly higher in patients with serum MtCK activity of >9.0 U/L compared to those with serum MtCK activity of ≤ 9.0 U/L even in patients with elevated liver stiffness value, >15 kPa. In conclusion, serum MtCK activity may be increased correlatively with the stage of liver fibrosis and hepatocellular damage. Increased serum MtCK activity is an independent risk for hepatocarcinogenesis in chronic hepatitis C patients.
authors.affiliation: Department of Clinical Laboratory Medicine Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan; Department of Gastroenterology Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Enooku
authors.forename: Hayato
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Yoko
authors.initials: Y
authors.lastname: Soroida
authors.forename: Ryunosuke
authors.initials: R
authors.lastname: Ohkawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kageyama
authors.forename: Baasanjav
authors.initials: B
authors.lastname: Uranbileg
authors.forename: Naoko
authors.initials: N
authors.lastname: Watanabe
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Tateishi
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Yoshida
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yatomi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ikeda
mesh_terms: D000368:Aged; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000150:complications; D052281:Creatine Kinase, Mitochondrial Form / Q000097:blood*; D005260:Female; D005355:Fibrosis; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications; D022781:Hepatocytes / Q000166:cytology; D006801:Humans; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000097:blood* / Q000150:complications; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010976:Platelet Count; D016016:Proportional Hazards Models; D012372:ROC Curve; D012306:Risk; D012680:Sensitivity and Specificity; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D012709:Serum Albumin; D052281:Creatine Kinase, Mitochondrial Form
keywords: hepatocellular carcinoma; liver fibrosis; ubiquitous mitochondrial creatine kinase