title: Serum ceruloplasmin levels correlate negatively with liver fibrosis in males with chronic hepatitis B: a new noninvasive model for predicting liver fibrosis in HBV-related liver disease.
abstract: OBJECTIVE
  This study aimed to investigate associations between ceruloplasmin (CP) levels, inflammation grade and fibrosis stages in patients with chronic hepatitis B (CHB) and to establish a noninvasive model to predict cirrhosis.
  
  
  METHODS
  Liver biopsy samples and sera were collected from 198 CHB patients randomized into a training group (n=109) and a validation group (n=89). CP levels were determined using nephelometric immunoassays. Relationships between CP and liver inflammation and fibrosis were analyzed by Spearman rank correlation. Receiver operator characteristic (ROC) curves were used to evaluate the diagnostic value of CP for determining liver fibrosis in CHB. The liver pathology-predictive model was built using multivariate logistic regression analysis to identify relevant indicators.
  
  
  RESULTS
  CP levels were lower in males than in females, lower in patients with inflammation stage G4 compared to other stages and lower in cirrhotic compared to non-cirrhotic patients. Using area under the curve (AUC) values, CP levels distinguished different stages of inflammation and fibrosis. Multivariate analysis showed that CP levels were all significantly associated with cirrhosis in males. A model was developed combining routine laboratory markers APPCI (alpha-fetoprotein [AFP], prothrombin time, and platelets [PLT] with CP) to predict fibrosis in CHB patients. The APPCI had a significantly greater AUC than FIB-4 (aspartate aminotransferase [AST]/ alanine aminotransferase [ALT]/PLT/age), APRI (AST/PLT ratio index), GPI (globin/PLT), and APGA (AST/PLT/gammaglutamyl transpeptidase [GGT]) models (all P-values<0.001).
  
  
  CONCLUSIONS
  CP levels correlate negatively and indirectly with inflammation and fibrosis stages in male CHB patients. The APPCI model uses routine laboratory variables with CP to accurately predict liver fibrosis in CHB.
authors.affiliation: Liver Center, First Affiliated Hospital, Fujian Medical University, Taijiang District, Fuzhou, Fujian Province, China.
authors.forename: Da-Wu
authors.initials: DW
authors.lastname: Zeng
authors.forename: Yu-Rui
authors.initials: YR
authors.lastname: Liu
authors.forename: Jie-Min
authors.initials: JM
authors.lastname: Zhang
authors.forename: Yue-Yong
authors.initials: YY
authors.lastname: Zhu
authors.forename: Su
authors.initials: S
authors.lastname: Lin
authors.forename: Jia
authors.initials: J
authors.lastname: You
authors.forename: You-Bing
authors.initials: YB
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Qi
authors.initials: Q
authors.lastname: Zheng
authors.forename: Jia-Ji
authors.initials: JJ
authors.lastname: Jiang
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002570:Ceruloplasmin / Q000378:metabolism*; D005260:Female; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000175:diagnosis; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis / Q000821:virology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012372:ROC Curve; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; D002570:Ceruloplasmin