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:
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.
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
Research 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.

Research motivation

The key to the retrospective cohort study is to explore DAA treatment in HCV-associated cirrhosis patients with HCC. Solutions to optimize DAAs treatment are explored to reduce the occurrence of HCC in patients with HCV-associated cirrhosis, and careful follow-up is needed.

Research objectives

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

Research methods

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.

Research results

The DAA treatment group was followed up for 1-84 mo, with a median follow-up of 28 mo, while the non-antiviral treatment group was followed up for 5-84 mo, with a median follow-up of 37 mo. Age > 58 [hazard ratio (HR) = 1.089; 95% confidence interval (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 DAA treatment didn’t show protective efficacy. After adjusting for confounding factors (age and sex), 27 cases of HCC occurred in the new DAA treatment group (236 cases), and there was no significant difference in the total incidence of HCC between the two groups (χ2 = 0.369, P = 0.544). In the new DAA treatment group, HCC incidence was 4.68/100PY (95%CI, 3.09-6.81), while it was 3.00/100PY (95%CI, 1.50-5.37) in the non-antiviral treatment group. The follow-up time of the new DAA treatment group was 1-84 mo (29.33 ± 16.20), the median follow-up time was 27 mo and the time of HCC occurrence in the new DAA treatment group was 5-66 mo. The incidence of HCC at 12, 24, 36 and 48 mo was 3.39%, 6.36%, 8.47% and 10.17% in the new DAA treatment group, and it was 0%, 0%, 3.39% and 9.32% in the non-antiviral treatment group, respectively.

Research conclusions

This is a novel assessment that provides theoretical insight into the impact of achieving SVR after DAA on HCC development in patients with HCV-associated cirrhosis. This study found that DAAs did not reduce the incidence of HCC in HCV-associated cirrhosis compared with no antiviral therapy, suggesting that the clinical priority of DAAs for patients with HCV is justified. We should also explore solutions to optimize DAAs therapy to reduce the occurrence of HCC in patients with HCV-associated cirrhosis.

Research perspectives

In future study, we should be focused on the research of the multicenter, large data, in order to more accurately assess DAAs influence on HCV-associated liver diseases in patients with HCC, thereby reducing the occurrence of HCC, and it can from common biochemical indicator, liquid biopsy, multiple sets of multi-angle discussion such as HCV-associated liver disease risk factors in patients with HCC.