title: Ceruloplasmin, a reliable marker of fibrosis in chronic hepatitis B virus patients with normal or minimally raised alanine aminotransferase.
abstract: OBJECTIVE
  To develop a non-invasive model to evaluate significant fibrosis and cirrhosis by investigating the association between serum ceruloplasmin (CP) levels and liver fibrosis in chronic hepatitis B (CHB) patients with normal or minimally raised alanine aminotransferase (ALT).
  
  
  METHODS
  Serum samples and liver biopsy were obtained from 193 CHB patients with minimally raised or normal ALT who were randomly divided into a training group (n= 97) and a validation group (n= 96). Liver histology was evaluated by the METAVIR scoring system. Receiver operator characteristic curves were applied to the diagnostic value of CP for measuring liver fibrosis in CHB patients. Spearman rank correlation analyzed the relationship between CP and liver fibrosis. A non-invasive model was set up through multivariate logistic regression analysis.
  
  
  RESULTS
  Serum CP levels individualized various fibrosis stagesviaarea under the curve (AUC) values. Multivariate analysis revealed that CP levels were significantly related to liver cirrhosis. Combining CP with serum GGT levels, a CG model was set up to predict significant fibrosis and liver cirrhosis in CHB patients with normal or minimally raised ALT. The AUC, sensitivity, specificity, positive predictive value, and negative predictive value were 0.84, 83.1%, 78.6%, 39.6%, and 96.5% to predict liver cirrhosis, and 0.789, 80.26%, 68.38%, 62.25%, and 84.21% to predict significant fibrosis. This model expressed a higher AUC than FIB-4 (age, ALT, aspartate aminotransferase, platelets) and GP (globulin, platelets) models to predict significant fibrosis (P= 0.019 and 0.022 respectively) and revealed a dramatically greater AUC than FIB-4 (P= 0.033) to predict liver cirrhosis.
  
  
  CONCLUSIONS
  The present study showed that CP was independently and negatively associated with liver fibrosis. Furthermore, we developed a novel promising model (CG), based on routine serum markers, for predicting liver fibrosis in CHB patients with normal or minimally raised ALT.
authors.affiliation: Da-Wu Zeng, Jing Dong, Jia-Ji Jiang, Yue-Yong Zhu, Yu-Rui Liu, Liver Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China.
authors.forename: Da-Wu
authors.initials: DW
authors.lastname: Zeng
authors.affiliation: Da-Wu Zeng, Jing Dong, Jia-Ji Jiang, Yue-Yong Zhu, Yu-Rui Liu, Liver Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.affiliation: Da-Wu Zeng, Jing Dong, Jia-Ji Jiang, Yue-Yong Zhu, Yu-Rui Liu, Liver Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China.
authors.forename: Jia-Ji
authors.initials: JJ
authors.lastname: Jiang
authors.affiliation: Da-Wu Zeng, Jing Dong, Jia-Ji Jiang, Yue-Yong Zhu, Yu-Rui Liu, Liver Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China.
authors.forename: Yue-Yong
authors.initials: YY
authors.lastname: Zhu
authors.affiliation: Da-Wu Zeng, Jing Dong, Jia-Ji Jiang, Yue-Yong Zhu, Yu-Rui Liu, Liver Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China.
authors.forename: Yu-Rui
authors.initials: YR
authors.lastname: Liu
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002570:Ceruloplasmin / Q000032:analysis*; D016009:Chi-Square Distribution; D005260:Female; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis / Q000821:virology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D012372:ROC Curve; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D002570:Ceruloplasmin; D000410:Alanine Transaminase
keywords: Ceruloplasmin; Chronic hepatitis B; Cirrhosis; Fibrosis; Liver biopsy