Cost-effectiveness of risk-stratified hepatocellular carcinoma screening using the age-male-albumin-bilirubin-platelets score-based stepwise enrichment approach in patients with cirrhosis

doi:10.3748/wjg.121840

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Observational Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastroenterol. Dec 14, 2026; 32(46): 121840
Published online Dec 14, 2026. doi: 10.3748/wjg.121840

Cost-effectiveness of risk-stratified hepatocellular carcinoma screening using the age-male-albumin-bilirubin-platelets score-based stepwise enrichment approach in patients with cirrhosis

Yun-Bo Zhang, Yu-Xuan Li, Wen-Di Zhang, Xian-Bin Hou, Rui Li, Ru-Yi Xia, Ming-Wang Shen, Zhuo-Ru Zou, Gui-Hua Zhuang

Yun-Bo Zhang, Yu-Xuan Li, Wen-Di Zhang, Xian-Bin Hou, Ming-Wang Shen, Zhuo-Ru Zou, Gui-Hua Zhuang, Department of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an 710061, Shaanxi Province, China

Rui Li, Heidelberg Institute of Global Health, Faculty of Medicine and University Hospital, Heidelberg University, Heidelberg 69120, Baden-Württemberg, Germany

Ru-Yi Xia, School of Public Health, Xi’an Medical University, Xi’an 710021, Shaanxi Province, China

Co-corresponding authors: Zhuo-Ru Zou and Gui-Hua Zhuang.

Author contributions: Zhuang GH and Zou ZR contributed equally to this work as co-corresponding authors; Zhang YB, Zhuang GH and Zou ZR conceived and designed the study; Zhang YB, Li YX, Zhang WD collected the data; Zhang YB analyzed the data, and carried out the analysis, wrote the first draft of the manuscript; Hou XB, Li R, Xia RY and Shen MW edited the manuscript; Zhuang GH and Zou ZR critically revised the manuscript; Zhang YB, Li YX, Zhang WD, Hou XB, Li R, Xia RY, Shen MW, Zou ZR, Zhuang GH contributed to writing the paper and agreed with the manuscript results and conclusions; all authors read and approved the final manuscript.

AI contribution statement: AI tools (specifically ChatGPT) were used solely for linguistic refinement and formatting assistance. No AI tool was involved in the generation of research data, interpretation of results, or formulation of conclusions. All AI-generated outputs were critically reviewed and revised by the authors.

Supported by the China National Science and Technology Major Project, No. 2023ZD0501400; National Natural Science Foundation of China, No. 82304206; and China Postdoctoral Science Foundation, No. BX20220254 and No. 2023M732773.

Institutional review board statement: This study was based on a Markov model using published secondary data and did not involve any direct interaction with human or animal subjects. Therefore, institutional review board approval was not required.

Informed consent statement: This study does not involve any human subjects, human data, or human tissue. Therefore, no informed consent was required from any participant.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article. None of the funders had any role in study design, data collection, data analysis, interpretation, decision to publish, or preparation of the manuscript.

STROBE statement: The authors have read the STROBE Statement—a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-a checklist of items.

Data sharing statement: All data generated or analysed during this study are included in this published article and its Supplementary material.

Corresponding author: Gui-Hua Zhuang, PhD, Professor, Department of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, No. 76 Yanta West Road, Xi’an 710061, Shaanxi Province, China. zhuanggh@mail.xjtu.edu.cn

Received: April 3, 2026
Revised: May 23, 2026
Accepted: June 4, 2026
Published online: December 14, 2026
Processing time: 200 Days and 20.7 Hours

Abstract

BACKGROUND

The age-male-albumin-bilirubin-platelets score-based stepwise enrichment approach sequentially applies common biomarkers, alpha-fetoprotein (AFP), and circulating cell-free DNA (cfDNA), offering a cost- and performance-balanced framework for hepatocellular carcinoma (HCC) risk stratification.

AIM

To evaluate whether incorporating this approach into HCC screening is cost-effective for Chinese patients with compensated cirrhosis and identify the optimal combined strategy.

METHODS

A Markov model was developed to evaluate 600 screening strategies combining whether to apply stratification with different screening frequencies and methods from the healthcare system perspective. Strategies were compared using incremental cost-effectiveness ratios (ICERs) based on quality-adjusted life-years (QALYs), with willingness-to-pay thresholds set at 1 × and 3 × China’s per-capita gross domestic product (GDP) in 2024 (United States dollar 13445).

RESULTS

All three non-dominated strategies under the 3 × GDP threshold are risk-stratified. Screening with ultrasonography (US) + AFP quarterly for high-risk and annually for low-risk groups, and screening with quarterly alternating US + AFP/gadoxetic-enhanced magnetic resonance imaging (Gd-MRI) for high-risk and six-monthly US + AFP for low-risk groups, are the most cost-effective under the 1 × and 3 × GDP thresholds, respectively (ICER = United States dollar 11137/QALY and United States dollar 31507/QALY). Both strategies have the highest probabilities of being cost-effective at their corresponding thresholds (0.58 and 0.24) in probabilistic sensitivity analysis. Even if re-stratification is required every two years, an approximately 40% reduction in cfDNA testing costs allows both strategies to remain probabilistically optimal, particularly the former strategy.

CONCLUSION

Risk-stratified HCC screening using the stepwise enrichment approach is more cost-effective than unstratified screening for Chinese compensated cirrhosis patients, with US + AFP at varying frequencies for high- and low-risk groups being the optimal combination. Stratified screening involving alternating US + AFP/Gd-MRI may be optimal only under higher willingness-to-pay thresholds.

Keywords: Hepatocellular carcinoma; Screening; Age-male-albumin-bilirubin-platelets; Risk stratification; Cost-effectiveness; Cell-free deoxyribonucleic acid

Core Tip: This study developed a Markov model to evaluate the cost-effectiveness of risk-stratified hepatocellular carcinoma screening using age-male-albumin-bilirubin-platelets score-based stepwise enrichment approach in compensated cirrhosis. A total of 600 screening strategies were evaluated, combining whether to apply stratification with different screening frequencies and methods. Stratified screening with ultrasonography (US) + alpha-fetoprotein (AFP) quarterly for high-risk and annually for low-risk groups, and screening with quarterly alternating US + AFP/gadoxetic-enhanced magnetic resonance imaging for high-risk and six-monthly US + AFP for low-risk groups, are the most cost-effective under the 1 × and 3 × gross domestic product thresholds, respectively. Furthermore, reducing cell-free DNA testing costs would boost the optimal strategies’ probability advantage, even if re-stratification is required more frequently.