Case Control Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Nov 6, 2018; 6(13): 600-610
Published online Nov 6, 2018. doi: 10.12998/wjcc.v6.i13.600
Iron metabolism disorders in patients with hepatitis B-related liver diseases
Yan-Hang Gao, Jing-Yun Wang, Pei-Yan Liu, Jing Sun, Xiao-Mei Wang, Rui-Hong Wu, Xiu-Ting He, Zheng-Kun Tu, Chun-Guang Wang, Hong-Qin Xu, Jun-Qi Niu
Yan-Hang Gao, Jing-Yun Wang, Pei-Yan Liu, Jing Sun, Xiao-Mei Wang, Rui-Hong Wu, Hong-Qin Xu, Jun-Qi Niu, Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun 130021, Jilin Province, China
Jing-Yun Wang, Department of Gastroenterology, Weihaiwei People’s Hospital, Weihai 264200, Shandong Province, China
Jing Sun, Department of Gastroenterology, Heping Hospital, Changzhi Medical College, Changzhi 046011, Shanxi Province, China
Xiu-Ting He, Department of Geriatrics, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Zheng-Kun Tu, Department of Translational Medicine, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Chun-Guang Wang, Department of Surgery, The Second Hospital of Jilin University, Changchun 130021, Jilin Province, China
Jun-Qi Niu, Jilin Provincial Key Laboratory of Infectious Diseases, Laboratory of Molecular Virology, Changchun 130021, Jilin Province, China
Author contributions: Niu JQ, Wang CG and Xu HQ designed the research; Niu JQ, Gao YH, Wang CG, Liu PY, Sun J, and He XT treated the patients and collected the materials and clinical data from patients; Wang JY, Wang XM, and Tu ZK performed the assays; Xu HQ analyzed the data; Gao YH and Xu HQ wrote the paper. Wang CG, Xu HQ, and Niu JQ are co-corresponding authors. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.
Supported by the National Science and Technology Major Project, No. 2014ZX10002002 and No. 2017ZX10202202; the National Key Research Plan “Precision Medicine Research” Key Project, No. 2017YFC0908103; the National Natural Science Foundation of China, No. 81700534; and Program for JLU Science and Technology Innovative Research Team, No. 2017TD-08.
Institutional review board statement: The study was reviewed and approved by the First Hospital Ethical Committee of Jilin University.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: Dataset available from the corresponding author at junqi_niu@163.com or hongqinxu86@jlu.edu.cn.
Open-Access: This 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 Non Commercial (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/
Correspondence to: Jun-Qi Niu, PhD, Professor, Department of Hepatology, First Hospital of Jilin University, No. 71, Xinmin Street, Changchun 130021, Jilin Province, China. junqi_niu@163.com
Telephone: +86-431-88783486 Fax: +86-431-85612468
Received: July 17, 2018
Peer-review started: July 17, 2018
First decision: August 25, 2018
Revised: September 16, 2018
Accepted: October 16, 2018
Article in press: October 16, 2018
Published online: November 6, 2018
Processing time: 113 Days and 0.7 Hours
ARTICLE HIGHLIGHTS
Research background

Chronic hepatitis B virus (HBV) infection affects 240 million people worldwide and can lead to chronic liver diseases including chronic hepatitis B (CHB), cirrhosis, and hepatocellular carcinoma (HCC). In managing chronic HBV infection, the objective is to detect liver injury early and then stop the progression of liver disease through effective treatment. To achieve this goal, a clear understanding of various factors involved in HBV pathogenesis is required. The relationship between HBV-related chronic liver diseases and levels of serum markers of iron metabolism and their impact on liver disease severity have not been well investigated. The aim of this study was to characterize changes in serum iron markers in patients with HBV-related diseases and to assess correlations between changes in iron metabolism and HBV-related liver injury.

Research motivation

In managing chronic HBV infection, the objective is to detect liver injury early and then stop the progression of liver disease through effective treatment. To achieve this goal, a clear understanding of various factors involved in HBV pathogenesis is required.

Research objectives

The aim of this study was to characterize changes in serum iron markers in patients with HBV-related diseases and assess correlations between changes in iron metabolism and HBV-related liver injury.

Research methods

This was a case-control study, which included 78 healthy controls, 78 CHB patients including 25 diagnosed by biopsy, 85 patients with HBV-related liver cirrhosis including 5 diagnosed by biopsy, and 77 with HBV-related HCC. Blood samples were collected from all patients after overnight fasting. Serum iron metabolism markers, HBV serological markers and HBV-DNA, and biochemical markers were determined with autoanalyzers. Liver biopsy was performed with a 16 G Tru-Cut needle guided by color Doppler ultrasound. A biopsy that was 1.5 cm or longer or a liver section that contained at least five portal tracts was considered eligible for diagnosis. The liver sections from each biopsy were stained with hematoxylin and eosin and Perls, respectively. Liver fibrosis was staged using the METAVIR scoring system. The SPSS program was used for all statistical analyses, and statistical significance was considered if a P-value < 0.05.

Research results

The serum ferritin levels were significantly higher in CHB, liver cirrhosis, and HCC groups compared with the control group. The median TIBC level was significantly lower in the CHB group, liver cirrhosis, and HBV-HCC patients than in healthy controls, as was the mean transferrin level in CHB, liver cirrhosis, and HCC patients relative to the values in controls. Among the three liver disease groups, serum iron, total iron binding capacity, and serum transferrin levels were significantly lower, and the hepcidin level was significantly higher in the patients with cirrhosis or HCC (P < 0.05) than in the patients with CHB. Serum ferritin and transferrin saturation levels increased proportionally to the extent of liver cirrhosis and poorer Child-Pugh scores (P < 0.05). The decreased serum iron and transferrin saturation levels significantly correlated with a smaller hepatocellular carcinoma tumor burden according to Barcelona Clinic Liver Cancer staging. There was a clear trend of an increase in iron deposition in the liver tissues with increased fibrosis, which became prominent at stages 3 and 4 (Figure 4A-F; P < 0.05). The iron level was barely detectable at stage 0 (Figure 4A), while prominent iron retention in hepatocytes was detected at S3 and S4 (Figure 4D and E). Iron deposition in liver cells was observed in 10%–50% of CHB patients. The mean iron level was significantly higher in severe fibrosis and cirrhosis compared with that in tissues with no or mild fibrosis. We also analyzed the relationships between serum hepcidin levels and demographic factors. Age, international normalized ratio, and HBV-DNA were independent factors associated with higher serum hepcidin. The cross-sectional study design limited the ability of this study to clarify causality between HBV-DNA load and altered hepcidin levels.

Research conclusions

Iron metabolism disorders occur in patients with HBV-related liver disease. The iron metabolism disorders vary in different stages of HBV-related liver diseases.

Research perspectives

The mechanism of iron metabolism disorders present in patients of HBV-related liver disease should be further studied in the future.