da Silva PGF, Barrocas JBP, Perazzo H, Villela-Nogueira L, Peixoto HR, Pereira GHS, Braga LNP, Chinzon M, de Silva JRL, Fernandes FF, Villela-Nogueira CA. Transient elastography and fibrosis-4 index as predictors of hepatocellular carcinoma in hepatitis C virus patients with sustained virological response. World J Gastroenterol 2025; 31(45): 112318 [DOI: 10.3748/wjg.v31.i45.112318]
Corresponding Author of This Article
Cristiane A Villela-Nogueira, MD, Full Professor, School of Medicine, Department of Internal Medicine, Federal University of Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco, 255 room 9E16 Cidade Universitária, Ilha do Fundão, Rio de Janeiro 21941617, Brazil. crisvillelanog@gmail.com
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Gastroenterology & Hepatology
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Retrospective Cohort Study
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Dec 7, 2025 (publication date) through Dec 6, 2025
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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
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da Silva PGF, Barrocas JBP, Perazzo H, Villela-Nogueira L, Peixoto HR, Pereira GHS, Braga LNP, Chinzon M, de Silva JRL, Fernandes FF, Villela-Nogueira CA. Transient elastography and fibrosis-4 index as predictors of hepatocellular carcinoma in hepatitis C virus patients with sustained virological response. World J Gastroenterol 2025; 31(45): 112318 [DOI: 10.3748/wjg.v31.i45.112318]
World J Gastroenterol. Dec 7, 2025; 31(45): 112318 Published online Dec 7, 2025. doi: 10.3748/wjg.v31.i45.112318
Transient elastography and fibrosis-4 index as predictors of hepatocellular carcinoma in hepatitis C virus patients with sustained virological response
Paula G F da Silva, Juliana B P Barrocas, Hugo Perazzo, Livia Villela-Nogueira, Helena R Peixoto, Gustavo H S Pereira, Lailiane N P Braga, Miriam Chinzon, Joyce R L de Silva, Flávia F Fernandes, Cristiane A Villela-Nogueira
Paula G F da Silva, Juliana B P Barrocas, Gustavo H S Pereira, Lailiane N P Braga, Miriam Chinzon, Joyce R L de Silva, Department of Gastroenterology and Hepatology, Bonsucesso Federal Hospital, Rio de Janeiro 21041020, Brazil
Hugo Perazzo, Evandro Chagas National Institute of Infectious Disease, Oswaldo Cruz Foundation, Rio de Janeiro 21040360, Brazil
Livia Villela-Nogueira, Helena R Peixoto, Cristiane A Villela-Nogueira, School of Medicine, Department of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941617, Brazil
Flávia F Fernandes, Pedro Ernesto University Hospital, University of the State of Rio de Janeiro, Rio de Janeiro 20551030, Brazil
Author contributions: Villela-Nogueira CA and Fernandes FF participated in the study’s conception, design, and final revision; Da Silva PGF, Fernandes FF, and Villela-Nogueira CA wrote the manuscript, were involved in interpreting data, and accessed and verified the study data; Da Silva PGF, Barrocas JBP, Perazzo H, Villela-Nogueira L, Peixoto HR, Pereira GHS, Braga LNP, Chinzon M, and de Silva JRL were involved in the acquisition of data and its interpretation, and in the follow-up of patients; Villela-Nogueira CA and Fernandes FF share the senior authors’ position; All authors critically reviewed and provided final approval of the manuscript; all authors were responsible for the decision to submit the manuscript for publication.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Clementino Fraga Filho University Hospital UFRJ CAAE (No. 1.654.467).
Informed consent statement: Due to the retrospective design of the study, the authors were waived to apply the informed consent form.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
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: The authors will be glad to share the database upon 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: Cristiane A Villela-Nogueira, MD, Full Professor, School of Medicine, Department of Internal Medicine, Federal University of Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco, 255 room 9E16 Cidade Universitária, Ilha do Fundão, Rio de Janeiro 21941617, Brazil. crisvillelanog@gmail.com
Received: July 24, 2025 Revised: August 25, 2025 Accepted: October 17, 2025 Published online: December 7, 2025 Processing time: 132 Days and 10.5 Hours
Abstract
BACKGROUND
People with compensated advanced chronic liver disease (cACLD) remain at high risk of hepatocellular carcinoma (HCC) even after hepatitis C virus (HCV) sustained virological response (HCV-SVR).
AIM
To evaluate transient elastography and fibrosis-4 (FIB-4) index as prognostic markers for HCC after HCV-SVR.
METHODS
This retrospective cohort study analyzed data from people with cALCD and HCV-SVR. cALCD was defined as baseline liver stiffness measurement (LSM) ≥ 10 kPa. The primary outcome was the occurrence of HCC. Data collected at baseline (pre-treatment) and 1 year after the end of treatment (1-year-EOT) of LSM, FIB-4 index, and laboratory results were analyzed. LSM and FIB-4 index were evaluated as independent predictors of HCC by a Cox regression analysis. Receiver operator characteristic curves, Kaplan-Meier curves, and Cox regression analysis were performed.
RESULTS
Total of 425 patients (65.2% female; mean age = 62 ± 10 years) were included. The median pre-treatment and 1-year-EOT LSM were respectively 15.0 kPa (interquartile range: 11.8-23.2) and 12 kPa (interquartile range: 7.9-19.9) (P < 0.001), with a 27% (interquartile range: 2.7%-43%) reduction after SVR. The median pre-treatment FIB-4 index was 2.94 (interquartile range: 1.89-4.85) and 1-year-EOT FIB-4 1.99 (interquartile range: 1.29-3.13) (P < 0.001). Neither LSM nor FIB-4 deltas were associated with HCC. A total of 26 participants (6%) developed HCC during a follow-up of 48 ± 23 months with an incidence of 15.3/1000 person-years. Age [hazard ratio (HR) = 1.06, 95% confidence interval (CI): 1.01-1.11; P = 0.02], baseline (HR = 1.05, 95%CI: 1.02-1.07) and 1-year-EOT LSM ≥ 20 kPa (HR = 4.49, 95%CI: 2.19-9.19; P < 0.001) and baseline (HR = 7.79, 95%CI: 2.31-26.32; P < 0.001) and 1-year-EOT FIB-4 index score ≥ 3.25 (HR = 3.14, 95%CI: 1.65-6.00; P < 0.001) were associated with incident HCC.
CONCLUSION
In cACLD-HCV SVR patients, pre-treatment or 1-year-EOT LSM ≥ 20 kPa and FIB-4 ≥ 3.25 but not their delta was associated with HCC. A single measure of LSM ≥ 20 kPa or FIB-4 ≥ 3.25, either pre-treatment or 1-year-EOT, would be necessary to predict the incidence of HCC in people with HCV-SVR.
Core Tip: This retrospective longitudinal study was conducted in two tertiary centers to evaluate noninvasive tests as predictive factors for developing hepatocellular carcinoma (HCC). The cohort included people with chronic hepatitis C virus infection and compensated advanced chronic liver disease, defined as pre-treatment liver stiffness measurement (LSM) ≥ 10 kPa, who achieved sustained virological response after direct-acting antivirals therapy. At pre-treatment and 1-year end of treatment, fibrosis-4 index score ≥ 3.25 and LSM ≥ 20 kPa were independently associated with the incidence of HCC.
