Retrospective Cohort Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jan 27, 2024; 16(1): 41-53
Published online Jan 27, 2024. doi: 10.4254/wjh.v16.i1.41
Direct-acting antivirals failed to reduce the incidence of hepatocellular carcinoma occurrence in hepatitis C virus associated cirrhosis: A real-world study
Xue-Mei Tao, Ming-Hui Zeng, You-Fei Zhao, Jia-Xin Han, Yu-Qiang Mi, Liang Xu
Xue-Mei Tao, Ming-Hui Zeng, You-Fei Zhao, Jia-Xin Han, Yu-Qiang Mi, Liang Xu, Clinical School of the Second People’s Hospital, Tianjin Medical University, Tianjin 300192, China
Xue-Mei Tao, Ming-Hui Zeng, You-Fei Zhao, Jia-Xin Han, Yu-Qiang Mi, Liang Xu, Department of Hepatology, Tianjin Second People’s Hospital, Tianjin 300192, China
Liang Xu, Department of Hepatology, Tianjin Research Institute of Liver Diseases, Tianjin 300192, China
Co-corresponding authors: Liang Xu and Yu-Qiang Mi.
Author contributions: Xu L, Mi YQ and Tao XM designed the study; Tao XM, Zeng MH and Zhao YF and Han JX performed the research; Tao XM carried out statistical analysis; Tao XM wrote the manuscript; Xu L and Mi YQ critical revised of the manuscript. All the authors have read and approved the final revision to be published. Xu L and Mi YQ, as co-corresponding authors, played an important and indispensable role in the experimental design, data interpretation, and manuscript writing. Xu L and Mi YQ applied for and received funding for this research project. Mi YQ was responsible for the conceptualization, design and supervision of the overall project and the revision of the article. Xu L was responsible for the design of the experiment, revision of the article, preparation and submission of the current version of the manuscript.
Supported by Chinese Foundation for Hepatitis Prevention and Control—Tian Qing Hepatitis Research Fund, No. TQGB20210175; Tianjin Key Medical Discipline (Specialty) Construction Project, TJYXZDXK-059B; Tianjin Health Science and Technology Project Key Discipline Special, TJWJ2022XK034; and Research project of Chinese Traditional Medicine and Chinese Traditional Medicine Combined With Western Medicine of Tianjin Municipal Health and Family Planning Commission, No. 2021022.
Institutional review board statement: The study was reviewed and approved by Medical Ethics Committee of Tianjin Second People's Hospital Approval Certificate of Ethical Review, and the certificate number: Tianjin Second People's Hospital Ethics Review word [2018] No. 21.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.
STROBE statement: The authors declare they have read the STROBE statement. The present manuscript was prepared and revised following the checklist of the STROBE statement.
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: Liang Xu, PhD, Chief Physician, Clinical School of the Second People’s Hospital, Tianjin Medical University, No. 7 South of Sudi Road, Nankai District, Tianjin 300192, China. xuyangliang2004@sina.com
Received: November 21, 2023
Peer-review started: November 21, 2023
First decision: December 5, 2023
Revised: December 18, 2023
Accepted: January 9, 2024
Article in press: January 9, 2024
Published online: January 27, 2024
Abstract
BACKGROUND

Direct-acting antivirals (DAAs) revolutionized the treatment of chronic hepatitis C virus (HCV)-associated disease achieving high rates of sustained virological response (SVR). However, whether DAAs can reduce the occurrence of hepatocellular carcinoma (HCC) in patients with HCV-associated cirrhosis who are at high risk have not been concluded.

AIM

To investigate the effect of DAAs on the occurrence of HCC in patients with HCV-associated cirrhosis after achieving SVR.

METHODS

Of 427 inpatients with HCV-associated cirrhosis were enrolled in Tianjin Second People's Hospital from January 2014 to April 2020. 118 patients weren’t received antiviral treatment with any reasons named non-antiviral treatment group, and 236 patients obtained from the 309 DAAs treatment patients according to the propensity score matching named DAAs treatment group. Demographic information and laboratory data were collected from baseline and the following up. Kaplan-Meier curve and Log-Rank test were used to compare the incidence and cumulative incidence of HCC between the two groups. Cox proportional risk regression was used to re-evaluate the risk factors for HCC.

RESULTS

HCC incidence was 4.68/100PY (95%CI, 3.09-6.81) in the DAAs treatment group, while it was 3.00/100PY (95%CI, 1.50-5.37) in the non-antiviral treatment group, and the relative risk was 1.82 (95%CI, 0.93-3.53, P > 0.05). The incidence of HCC at 12, 24, 36 and 48 months was 3.39%, 6.36%, 8.47% and 10.17% in the DAAs treatment group, and it was 0%, 0%, 3.39% and 9.32% in the non-antiviral treatment group, respectively. Age > 58 [hazard ratio (HR) = 1.089; 95%CI, 1.033-1.147; P = 0.002] and liver stiffness measurement > 27.85 kPa (HR = 1.043; 95%CI, 1.022-1.065; P = 0.000) were risk factors for HCC in all patients (n = 427), and DAAs treatment didn’t show protective efficacy.

CONCLUSION

DAAs treatment seems failed to reduce the incidence of HCC occurrence in HCV-associated cirrhosis in 48 months, and even increased the incidence of HCC in 36 months.

Keywords: Direct-acting antivirals, Sustained viral response, Cirrhosis, Hepatocellular carcinoma, Risk factor

Core Tip: We evaluated the effect of direct-acting antivirals (DAAs) on the development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-associated cirrhosis during long-term follow-up. We performed propensity score matching, Kaplan-Meier curve and Log-Rank test, the incidence and cumulative incidence of HCC in DAAs treatment group (n = 236) and non-antiviral treatment group (n = 118) were retrospectively evaluated, and the risk factors for HCC were evaluated by Cox regression. We found that DAAs treatment of HCV-associated cirrhosis failed to reduce the incidence of HCC over 48 mo. Age and liver stiffness measurement were risk factors for developing HCC in all patients (n = 427), and DAAs treatment showed no protective effect.