Dang HNN, Viet Luong T, Minh Vu H, Nguyen KY, Tran Xuan H, Hoang Thi BN. Longitudinal fibrosis-4 monitoring: A promising approach for hepatocellular carcinoma risk stratification in treatment-naïve chronic hepatitis C. World J Gastrointest Oncol 2026; 18(11): 120525 [DOI: 10.4251/wjgo.120525]
Corresponding Author of This Article
Bich Ngoc Hoang Thi, MD, Researcher, Department of Outpatient, Gia An 115 Hospital, 05, 17A Street, Binh Tri Dong B Ward, Binh Tan District, Ho Chi Minh City 700000, Viet Nam. hoangngoc.yhue.a@gmail.com
Research Domain of This Article
Gastroenterology & Hepatology
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editorial
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World J Gastrointest Oncol. Nov 15, 2026; 18(11): 120525 Published online Nov 15, 2026. doi: 10.4251/wjgo.120525
Longitudinal fibrosis-4 monitoring: A promising approach for hepatocellular carcinoma risk stratification in treatment-naïve chronic hepatitis C
Hai Nguyen Ngoc Dang, Thang Viet Luong, Hung Minh Vu, Kim Yen Nguyen, Hung Tran Xuan, Bich Ngoc Hoang Thi
Hai Nguyen Ngoc Dang, Faculty of Medicine, School of Medicine and Pharmacy, Duy Tan University, Da Nang 550000, Viet Nam
Hai Nguyen Ngoc Dang, Thang Viet Luong, Menzies Institute for Medical Research, University of Tasmania, Hobart 7000, Tasmania, Australia
Hung Minh Vu, University of Medicine and Pharmacy, Hue University, Hue 530000, Viet Nam
Kim Yen Nguyen, Department of Internal Medicine, Phuc Hung Private General Hospital, Quang Ngai 570000, Viet Nam
Hung Tran Xuan, Department of Gastroenterology and Hepatology, Nghe An General Friendship Hospital, Nghe An 460000, Viet Nam
Bich Ngoc Hoang Thi, Department of Cardiology, Gia An 115 Hospital, Ho Chi Minh City 700000, Viet Nam
Co-first authors: Hai Nguyen Ngoc Dang and Thang Viet Luong.
Author contributions: Dang HNN and Luong TV are co-first authors and contributed equally to the study’s conception, methodology, and drafting of the original manuscript; Vu HM, Nguyen KY, and Xuan HT contributed to the literature review, data interpretation, overall supervision, and manuscript writing and editing; Hoang Thi BN is the corresponding author and contributed to overall supervision, critical revisions, and correspondence; all the authors read and approved the final version of the manuscript.
AI contribution statement: We confirm that ChatGPT was used only for minor language support, specifically for checking spelling and grammar during manuscript preparation. The entire content of the manuscript was written and fully controlled by the authors, and no AI tools were used to generate any part of the scientific content. The authors take full responsibility for the accuracy and integrity of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Bich Ngoc Hoang Thi, MD, Researcher, Department of Outpatient, Gia An 115 Hospital, 05, 17A Street, Binh Tri Dong B Ward, Binh Tan District, Ho Chi Minh City 700000, Viet Nam. hoangngoc.yhue.a@gmail.com
Received: March 2, 2026 Revised: March 20, 2026 Accepted: May 18, 2026 Published online: November 15, 2026 Processing time: 238 Days and 10.6 Hours
Abstract
A substantial proportion of patients with chronic hepatitis C virus infection remain untreated worldwide, sustaining a cumulative and age-dependent risk of hepatocellular carcinoma, particularly in resource-limited settings. Conventional risk stratification relies on baseline “snapshots” of fibrosis stage and single-time-point biomarkers, which may fail to capture the dynamic biology of fibrogenesis and carcinogenesis. In a long-term retrospective cohort of treatment-naïve patients with chronic hepatitis C virus published in the World Journal of Gastrointestinal Oncology, Li et al reported that a 3-year increase in the fibrosis-4 (FIB-4) index (ΔFIB-4 ≥ 1.0) independently predicted subsequent hepatocellular carcinoma (adjusted hazard ratio approximately 2.7), with the increasing trajectory group exhibiting a high long-term cumulative incidence. These findings suggest that longitudinal biomarker trajectories may refine long-term risk stratification beyond baseline staging, although the timing and actionable thresholds require prospective validation. Biologically, progressive increases in FIB-4 may reflect ongoing extracellular matrix remodeling, inflammation-driven microenvironmental shifts, and vascular alterations that promote tumor development. However, interpretation must account for age-related score drift, biological variability, and nonhepatic confounding. We propose a pragmatic framework integrating threshold-crossing and slope-based monitoring, combining serial FIB-4 with alpha-fetoprotein and key demographic modifiers. High-risk longitudinal patterns may warrant the use of confirmatory elastography and the consideration of intensified surveillance, pending prospective validation. Prospective studies are needed to standardize longitudinal cutoffs and validate clinical implementation.
Core Tip: Longitudinal fibrosis-4 (FIB-4) monitoring may improve hepatocellular carcinoma risk stratification in untreated chronic hepatitis C beyond a single baseline assessment. Rising FIB-4 trajectories may reflect ongoing fibrogenesis and progressive portal remodeling, but interpretation requires caution because of age-related drift, biological variability, and nonhepatic confounding. At present, longitudinal ΔFIB-4 should be viewed mainly as a tool for long-term risk enrichment. High-risk patterns may warrant confirmatory elastography and consideration of closer surveillance, pending prospective validation.
