Published online Nov 21, 2016. doi: 10.3748/wjg.v22.i43.9586
Peer-review started: July 13, 2016
First decision: August 22, 2016
Revised: September 18, 2016
Accepted: October 10, 2016
Article in press: October 10, 2016
Published online: November 21, 2016
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).
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.
Serum CP levels individualized various fibrosis stages via area 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.
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.
Core tip: To date, few non-invasive approaches have been developed to evaluate liver fibrosis and no studies have proposed measuring ceruloplasmin (CP) levels for predicting liver fibrosis in chronic hepatitis B (CHB) virus patients with normal or minimally raised alanine aminotransferase (ALT). This study showed CP was independently and negatively associated with liver fibrosis. Furthermore, a simple and accurate CG model was developed to predict significant liver fibrosis and cirrhosis in CHB patients with normal or mildly elevated ALT. This model may be a valuable tool to replace liver biopsy in this category of hepatitis B virus-infected patients.