Observational Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2023; 29(35): 5166-5177
Published online Sep 21, 2023. doi: 10.3748/wjg.v29.i35.5166
Lowering the threshold of alanine aminotransferase for enhanced identification of significant hepatic injury in chronic hepatitis B patients
Hong-Sheng Yu, Hao Jiang, Ming-Kai Li, Bi-Lan Yang, Abdukyamu Smayi, Jian-Ning Chen, Bin Wu, Yi-Dong Yang
Hong-Sheng Yu, Hao Jiang, Ming-Kai Li, Bi-Lan Yang, Abdukyamu Smayi, Bin Wu, Yi-Dong Yang, Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China
Hong-Sheng Yu, Hao Jiang, Ming-Kai Li, Bi-Lan Yang, Abdukyamu Smayi, Bin Wu, Yi-Dong Yang, Department of Liver Disease, Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou 510630, Guangdong Province, China
Jian-Ning Chen, Department of Pathology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China
Author contributions: Yu HS and Jiang H have contributed equally to this work; Yu HS and Jiang H designed the study, performed the statistical analysis, and drafted the manuscript; Li MK, Yang BL, Smayi A and Chen JN collected the clinical data and then reviewed the data; Wu B and Yang YD revised the manuscript; Yang YD and Wu B were responsible for the study conception, design, data, analysis; All authors have read and approved the manuscript.
Supported by The Natural Science Foundation of Guangdong Province for Distinguished Young Scholar, No. 2022B1515020024; National Natural Science Foundation of China, No. 82070574; and The Natural Science Foundation Team Project of Guangdong Province, No. 2018B030312009.
Institutional review board statement: The study was reviewed and approved by the Third Affiliated Hospital of Sun Yat-Sen University. No. [2019]02-530-01.
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
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: Yi-Dong Yang, PhD, Associate Professor, Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou 510630, Guangdong Province, China. yangyd6@mail.sysu.edu.cn
Received: July 2, 2023
Peer-review started: July 2, 2023
First decision: July 14, 2023
Revised: July 22, 2023
Accepted: August 31, 2023
Article in press: August 31, 2023
Published online: September 21, 2023
Processing time: 74 Days and 4.6 Hours
Abstract
BACKGROUND

The clinical and histological features of chronic hepatitis B (CHB) patients who fall into the "grey zone (GZ)" and do not fit into conventional natural phases are unclear.

AIM

To explore the impact of varying the threshold of alanine aminotransferase (ALT) levels in identifying significant liver injury among GZ patients.

METHODS

This retrospective analysis involved a cohort of 1617 adult patients diagnosed with CHB who underwent liver biopsy. The clinical phases of CHB patients were determined based on the European Association for the Study of the Liver 2017 Clinical Practice Guidelines. GZ CHB patients were classified into four groups: GZ-A (HBeAg positive, normal ALT levels, and HBV DNA ≤ 107 IU/mL), GZ-B (HBeAg positive, elevated ALT levels, and HBV DNA < 104 or > 107 IU/mL), GZ-C (HBeAg negative, normal ALT levels, and HBV DNA ≥ 2000 IU/mL), and GZ-D (HBeAg negative, elevated ALT levels, and HBV DNA ≤ 2000 IU/mL). Significant hepatic injury (SHI) was defined as the presence of notable liver inflammation (≥ G2) and/or significant fibrosis (≥ S2).

RESULTS

The results showed that 50.22% of patients were classified as GZ, and 63.7% of GZ patients developed SHI. The study also found that lowering the ALT treatment thresholds to the American Association for the Study of Liver Diseases 2018 treatment criteria (35 U/L for men and 25 U/L for women) can more accurately identify patients with significant liver damage in the GZ phases. In total, the proportion of patients with ALT ≤ 40 U/L who required antiviral therapy was 64.86% [(221 + 294)/794]. When we lowered the ALT treatment threshold to the new criteria (30 U/L for men and 19 U/L for women), the same outcome was revealed, and the proportion of patients with ALT ≤ 40 U/L who required antiviral therapy was 75.44% [(401 + 198)/794]. Additionally, the proportion of SHI was 49.1% in patients under 30 years old and increased to 55.3% in patients over 30 years old (P = 0.136).

CONCLUSION

These findings suggest the importance of redefining the natural phases of CHB and using new ALT treatment thresholds for better diagnosis and management of CHB patients in the GZ phases.

Keywords: Chronic hepatitis B; Grey zone; Indeterminate phase; Alanine aminotransferase; Antiviral therapy

Core Tip: In clinical practice, 27.8%-55% of chronic hepatitis B patients fall into the “grey zone” or “indeterminate phase” that does not meet the diagnostic criteria of the traditional stages. Additionally, there is still debate regarding how best to treat these grey zone (GZ) patients and the advantages of antiviral therapy. Hence, we evaluated the clinical and histological characteristics, and additionally explored the impact of adjusting the threshold of alanine aminotransferase (ALT) in identifying significant liver injury among GZ patients. Based on these data, lowering ALT thresholds can more accurately identify patients with significant hepatic injury at an earlier stage and reduce the need for unnecessary liver biopsies.