Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2020; 26(27): 3952-3962
Published online Jul 21, 2020. doi: 10.3748/wjg.v26.i27.3952
Serum ceruloplasmin can predict liver fibrosis in hepatitis B virus-infected patients
Na-Ling Kang, Jie-Min Zhang, Meng-Xin Lin, Xu-Dong Chen, Zu-Xiong Huang, Yue-Yong Zhu, Yu-Rui Liu, Da-Wu Zeng
Na-Ling Kang, Yue-Yong Zhu, Yu-Rui Liu, Da-Wu Zeng, Liver Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
Jie-Min Zhang, Department of Pharmacy, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
Meng-Xin Lin, Department of Infectious Diseases, The First Hospital of Quanzhou Affiliated with Fujian Medical University, Quanzhou 362000, Fujian Province, China
Xu-Dong Chen, Department of Gastroenterology, the 910th Hospital of the People's Liberation Army, Quanzhou 362000, Fujian Province, China
Zu-Xiong Huang, Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China
Author contributions: Kang NL, Zhang JM, Lin MX, and Huang ZX contributed equally to this work; Kang NL, Zeng DW, and Liu YR conceived and designed the experiments; Kang NL, Zhang JM, and Zeng DW performed the experiments; Chen XD, Huang ZX, Lin MX, Zhang JM, and Zhu YY analyzed the data; Kang NL, Zhang JM, Chen XD, Huang ZX, and Lin MX contributed reagents/materials/analysis tools; Kang NL, Zhang JM, and Zeng DW wrote the manuscript.
Supported by the Science and Technology Department of Fujian Province, No. 2018J01164; Quanzhou Science and Technology Bureau Planning Project, No. 2019N019S.
Institutional review board statement: This study was approved by the Institutional Review Board of Fujian Medical University.
Informed consent statement: The need for informed consent was waived due to the retrospective nature of the study.
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Da-Wu Zeng, MD, PhD, Associate Chief Physician, Doctor, Liver Center, The First Affiliated Hospital, Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou 350005, Fujian Province, China. zengdw1980@fjmu.edu.cn
Received: March 17, 2020
Peer-review started: March 17, 2020
First decision: April 25, 2020
Revised: May 6, 2020
Accepted: June 30, 2020
Article in press: June 30, 2020
Published online: July 21, 2020
Abstract
BACKGROUND

The presence of significant liver fibrosis in hepatitis B virus (HBV)-infected individuals with persistently normal serum alanine aminotransferase (PNALT) levels is a strong indicator for initiating antiviral therapy. Serum ceruloplasmin (CP) is negatively correlated with liver fibrosis in HBV-infected individuals.

AIM

To examine the potential value of serum CP and develop a noninvasive index including CP to assess significant fibrosis among HBV-infected individuals with PNALT.

METHODS

Two hundred and seventy-five HBV-infected individuals with PNALT were retrospectively evaluated. The association between CP and fibrotic stages was statistically analyzed. A predictive index including CP [Ceruloplasmin hepatitis B virus (CPHBV)] was constructed to predict significant fibrosis and compared to previously reported models.

RESULTS

Serum CP had an inverse correlation with liver fibrosis (r = -0.600). Using CP, the areas under the curves (AUCs) to predict significant fibrosis, advanced fibrosis, and cirrhosis were 0.774, 0.812, and 0.853, respectively. The CPHBV model was developed using CP, platelets (PLT), and HBsAg levels to predict significant fibrosis. The AUCs of this model to predict significant fibrosis, advanced fibrosis, and cirrhosis were 0.842, 0.920, and 0.904, respectively. CPHBV was superior to previous models like the aspartate aminotransferase (AST)-to-PLT ratio index, Fibrosis-4 score, gamma-glutamyl transpeptidase-to-PLT ratio, Forn’s score, and S-index in predicting significant fibrosis in HBV-infected individuals with PNALT.

CONCLUSION

CPHBV could accurately predict liver fibrosis in HBV-infected individuals with PNALT. Therefore, CPHBV can be a valuable tool for antiviral treatment decisions.

Keywords: Ceruloplasmin, Liver fibrosis, Chronic hepatitis B infection, Serum alanine aminotransferase, Noninvasive model, Receiver-operating characteristic

Core tip: Chronic hepatitis B virus (HBV)-infected individuals with persistently normal serum alanine aminotransferase (PNALT) levels may develop severe liver fibrosis, which requires antiviral therapy. Following up on our previous findings, this multicenter, cross-sectional study showed that ceruloplasmin (CP) has an inverse correlation with liver fibrosis and is a promising predictive marker for liver fibrosis among HBV-infected individuals with PNALT. We developed a noninvasive model (ceruloplasmin hepatitis B virus) using CP, platelets, and HBsAg levels to identify various stages of fibrosis among HBV-infected individuals with PNALT. Our model could reduce the need for liver biopsy before antiviral treatment.