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Observational Study
Copyright ©The Author(s) 2026. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Feb 27, 2026; 18(2): 113348
Published online Feb 27, 2026. doi: 10.4254/wjh.v18.i2.113348
Predictive tool for evident histological liver injury in chronic hepatitis B patients: Development and validation
Zhong-Shang Dai, Xin Cao, Yong-Fang Jiang, Bo He
Zhong-Shang Dai, Bo He, Department of Infectious Diseases, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
Xin Cao, Department of Rheumatology and Immunology, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
Yong-Fang Jiang, Department of Infectious Diseases, The Second Xiangya Hospital of Central South University, Clinical Medical Research Center for Viral Hepatitis in Hunan Province, Changsha 410011, Hunan Province, China
Co-first authors: Zhong-Shang Dai and Xin Cao.
Author contributions: Dai ZS and Cao X wrote the main manuscript text and prepared figures and tables; He B designed the study; Dai ZS is responsible for data collection; Jiang YF analyzed data. All authors have reviewed and approved the final manuscript. Dai ZS and Cao X contributed equally to this work as co-first authors.
Supported by National Key R&D Program of China, No. 2019YFE0190800.
Institutional review board statement: This study was approved by the Institutional Review Board from the Second Xiangya Hospital of Central South University (No. 2020-047) and conducted by the Declaration of Helsinki.
Informed consent statement: All patients were offered informed consent.
Conflict-of-interest statement: All study participants or their legal guardian provided informed written consent regarding personal and medical data collection prior to study enrolment.
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.
Data sharing statement: Data is available from the corresponding author on a reasonable request.
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: Bo He, Department of Infectious Diseases, The Second Xiangya Hospital of Central South University, No. 139 Renmin Middle Road, Changsha 410011, Hunan Province, China. hebo2017@csu.edu.cn
Received: August 25, 2025
Revised: October 23, 2025
Accepted: December 23, 2025
Published online: February 27, 2026
Processing time: 174 Days and 9.1 Hours
Abstract
BACKGROUND

Chronic hepatitis B (CHB) is a leading cause of liver-related mortality, progressing to fibrosis, cirrhosis, and hepatocellular carcinoma. Existing noninvasive tools (e.g., aspartate aminotransferase to platelet ratio index, fibrosis-4 index, liver stiffness measurement) and invasive liver biopsy have limitations in assessing evident histological liver injury (EHLI), highlighting the need for novel predictive models.

AIM

To develop and validate a predictive model for EHLI in CHB patients using a cohort from Hunan Province, China, to facilitate early risk identification and optimize resource allocation.

METHODS

This observational real-world study enrolled 223 CHB patients (August 2020 to March 2022) from the Second Xiangya Hospital, divided into development (n = 159) and validation (n = 64) cohorts (7:3 ratio). EHLI was defined as Ishak fibrosis stage ≥ 3 and/or histologic activity index ≥ 9. Variables were screened via univariable logistic regression and least absolute shrinkage and selection operator regression, and a multivariable logistic regression model and nomogram were constructed. Performance was evaluated using area under the curve (AUC), calibration plots, Hosmer-Lemeshow test, and decision curve analysis (DCA). Gene expression profiles were analyzed to identify immune-related pathways.

RESULTS

L59, platelet count (PLT), alanine transaminase (ALT), and aspartate transaminase (AST) were identified as independent predictors of EHLI. The model showed high discriminative ability, with AUC of 0.921 [95% confidence interval (CI): 0.880-0.963] in the development cohort and 0.959 (95%CI: 0.910-1.0) in the validation cohort, demonstrating a 20%-32% relative improvement in AUC over conventional noninvasive scores. Calibration plots demonstrated good agreement between predicted and observed EHLI, and DCA confirmed clinical utility (threshold probabilities: 20%-80%). Transcriptomic analysis identified 210 differentially expressed genes, with hub genes (e.g., COL1A2) and transforming growth factor-β/Smad pathway involvement linked to liver injury.

CONCLUSION

A novel nomogram incorporating L59, PLT, ALT, and AST robustly predicts EHLI in CHB patients. This model, using routinely measured variables, aids clinical decision-making and optimizes resource allocation.

Keywords: Chronic hepatitis B; Evident histological liver injury; Predictive model; Performance; Clinical applicability

Core Tip: This study developed and validated a novel nomogram incorporating L59, platelet count, alanine aminotransferase, and aspartate aminotransferase to predict evident histological liver injury (Ishak ≥ 3 or histologic activity index ≥ 9) in chronic hepatitis B patients. The model demonstrated high accuracy (area under the curve 0.921-0.959) and clinical utility, supported by transcriptomic insights implicating COL1A2 and transforming growth factor-β/Smad pathways. This tool enables noninvasive risk stratification, optimizing resource allocation and guiding early intervention.