Retrospective Cohort Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2019; 25(29): 3985-3995
Published online Aug 7, 2019. doi: 10.3748/wjg.v25.i29.3985
Liquid biopsy for non-invasive assessment of liver injury in hepatitis B patients
Wen-Ying Xia, Li Gao, Er-Hei Dai, Dan Chen, Er-Fu Xie, Li Yang, Shi-Chang Zhang, Bing-Feng Zhang, Jian Xu, Shi-Yang Pan
Wen-Ying Xia, Li Gao, Dan Chen, Er-Fu Xie, Shi-Chang Zhang, Bing-Feng Zhang, Jian Xu, Shi-Yang Pan, Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
Er-Hei Dai, Li Yang, Department of Laboratory Medicine, the Fifth Hospital of Shijiazhuang, Shijiazhuang 050021, Hebei Province, China
Author contributions: Xia WY, Gao L, and Dai EH contributed equally to this work as co-first authors and finished the major experiments; Pan SY designed the research; Chen D, Xie EF, and Yang L collected and analyzed the data; Gao L and Zhang SC wrote the paper; Zhang BF and Xu J critically revised the manuscript for important content.
Supported by the National Natural Science Foundation of China, No. 81672100 and No. 81371894; the Key Laboratory for Laboratory Medicine of Jiangsu Province of China, No. ZDXKB2016005; and Jiangsu Provincial Commission of Health and Family Planning, No. H201609.
Institutional review board statement: This study was approved for publication by our Institutional Reviewer.
Informed consent statement: All study participants or their legal guardian provided informed written consent for personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: All authors have no conflict of interest related to the manuscript.
Data sharing statement: The original anonymous dataset is available on request from the corresponding author at sypan@njmu.edu.cn.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to STROBE Statement-checklist of items.
Open-Access: This article is an open-access article which 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/
Corresponding author: Shi-Yang Pan, MD, Professor, Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing 210029, Jiangsu Province, China. sypan@njmu.edu.cn
Telephone: +86-25-68303452
Received: March 26, 2019
Peer-review started: March 26, 2019
First decision: May 24, 2019
Revised: June 13, 2019
Accepted: July 5, 2019
Article in press: July 3, 2019
Published online: August 7, 2019
ARTICLE HIGHLIGHTS
Research background

Hepatitis B is a major public health problem in China. It is important that the severity of liver injury is evaluated accurately for clinical treatment. Liver biopsy is considered the gold standard method to stage liver disease. However, it is not widely used in resource-limited settings. Therefore, the methods of non-invasive liquid biopsy need to be explored for assessment of liver injury.

Research motivation

Plasma DNA quantification was proved to be a potential marker for cell damage, which may be a non-invasive method for evaluating the severity of liver injury. However, the application of plasma DNA quantification still needs to be investigated in patients with hepatitis B.

Research objectives

The aim of this study was to evaluate liver injury in hepatitis B patients using quantified cell free DNA combined with other serum biomarker as a liquid biopsy-based method.

Research methods

A cohort of 663 subjects including 313 hepatitis B patients and 350 healthy controls were enrolled. Ultrasound-guided liver biopsies followed by histopathological assessments were performed for the 263 chronic hepatitis B patients to determine the degree of liver injury. Cell-free DNA was quantified using a novel duplex real-time polymerase chain reaction assay.

Research results

Compared with healthy controls, patients with hepatitis B virus (HBV) infection had significantly higher plasma DNA, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and HBV DNA levels (P < 0.01). Serum ALT, AST, bilirubin, and plasma DNA levels of patients with marked-severe inflammation were significantly higher than those of patients with mild-moderate inflammation (P < 0.01). There was a statistically significant correlation between hepatocyte inflammation severity and serum bilirubin (R2 = 0.673, P < 0.01) or plasma DNA (R2 = 0.597, P < 0.01) levels. The area under the curves of serum ALT, bilirubin, plasma DNA, and their combination to distinguish between patients with mild–moderate and marked-severe inflammation were 0.8059, 0.7910, 0.7921, and 0.9564, respectively.

Research conclusions

The combination of plasma DNA, serum ALT, and bilirubin could be a candidate liquid biopsy for non-invasive assessment of liver injury in hepatitis B patients.

Research perspectives

The combination of plasma DNA, serum ALT, and bilirubin as a novel liquid biopsy technique is expected to assist in making more precise diagnoses for hepatitis B patients, which will be validated in multiple clinical centers in the future.