Retrospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jan 27, 2022; 14(1): 260-273
Published online Jan 27, 2022. doi: 10.4254/wjh.v14.i1.260
Correlation of hepatitis B surface antigen expression with clinicopathological and biochemical parameters in liver biopsies: A comprehensive study
Anil Alpsoy, Haydar Adanir, Zeynep Bayramoglu, Gulsum Ozlem Elpek
Anil Alpsoy, Zeynep Bayramoglu, Gulsum Ozlem Elpek, Department of Pathology, Akdeniz University, Medical School, Antalya 07070, Turkey
Haydar Adanir, Department of Gastroenterology, Akdeniz University, Medical School, Antalya 07070, Turkey
Author contributions: Alpsoy A, Bayramoglu Z, Adanir H and Elpek GO designed the study and collected materials; Elpek GO and Alpsoy A evaluated the histopathological findings; Adanir H provided analytical tools; all authors assessed the results; Elpek GO and Alpsoy A wrote the manuscript; Elpek GO and Adanir H critically revised the draft; all the authors checked the final version of the manuscript.
Institutional review board statement: The study was reviewed and approved by the Akdeniz University Clinical Research Institutional Board (approval No. 16-012-211).
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: There is no conflict of interest.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Gulsum Ozlem Elpek, MD, Professor, Research Assistant Professor, Department of Pathology, Akdeniz University, Medical School, Dumlupınar Bulvarı, Antalya 07070, Turkey. elpek@akdeniz.edu.tr
Received: May 15, 2021
Peer-review started: May 15, 2021
First decision: July 8, 2021
Revised: July 10, 2021
Accepted: December 31, 2022
Article in press: December 31, 2021
Published online: January 27, 2022
Processing time: 250 Days and 17.7 Hours
Abstract
BACKGROUND

Chronic viral B hepatitis (CHB) is a potentially life-threatening liver disease that may progress to liver failure and cirrhosis. Currently, although combinations of different laboratory methods are used in the follow-up and treatment of CHB, the failure of these procedures in some cases has led to the necessity of developing new approaches. In CHB, the intrahepatic expression pattern of viral antigens, including hepatitis B surface antigen (HBsAg), is related to different phases of inflammation. However, many studies have focused on the intracytoplasmic properties of HBsAg staining, and HBsAg positivity in liver tissue has not been evaluated by objective quantitative methods.

AIM

To investigate the relationship of image analysis-based quantitative HBsAg expression and its staining patterns with clinicopathological factors and treatment in CHB.

METHODS

A total of 140 liver biopsies from treatment-naïve cases with CHB infection were included in this study. Following diagnosis, all patients were treated with entecavir (0.5 mg) and followed up at three-month intervals. The percentage of immunohistochemical HBsAg (p-HBsAg) expression in the liver was determined in whole tissue sections of biopsies from each case by image analysis. The immunohistochemical staining pattern was also evaluated separately according to 3 different previously defined classifications.

RESULTS

A positive correlation between p-HBsAg and serum levels of hepatitis B virus (HBV) DNA and HBsAg was observed (P < 0.001). The p-HBsAg value was significantly higher in younger patients than in older patients. When the groups were categorized according to the hepatitis B e antigen (HBeAg) status in HBeAg-positive cases, p-HBsAg was correlated with HBV DNA, hepatitis activity index (HAI) and fibrosis scores (P < 0.001). In this group, p-HBsAg and HBsAg expression patterns were also correlated with the viral response (VR) and the serological response (SR) (P < 0.001). Multivariate analysis revealed that p-HBsAg was an independent predictor of either VR or SR (P < 0.001). In HBeAg-negative patients, although HBsAg expression patterns were correlated with both HAI and fibrosis, no relationship was observed among p-HBsAg, clinicopathological factors and VR.

CONCLUSION

In pretreatment liver biopsies, the immunohistochemical determination of HBsAg expression by quantitative methods, beyond its distribution within the cell, may be a good predictor of the treatment response, especially in HBeAg-positive cases.

Keywords: Hepatitis B; Hepatitis B surface antigens; Hepatitis B e antigens; Fibrosis; Immunohistochemistry; Image analysis

Core Tip: This report describes a study that investigated image analysis-based quantitative hepatitis B surface antigen (HBsAg) expression and its different staining patterns in liver biopsies from patients with chronic viral B hepatitis (CHB) and correlated them with clinicopathological factors and treatment. Our findings confirmed the association of cytoplasmic HBsAg staining patterns with disease activity. Besides, the determination of immunohistochemical HBsAg expression by image analysis may be an important predictor of the response to therapy, especially in hepatitis B e antigen-positive cases. Accordingly, evaluation of the percentage of HBsAg expression by objective methods in liver tissues from treatment-naïve CHB patients might provide a useful tool in the follow-up and treatment of this disease.