Outcomes and predictors of treatment failure following direct-acting antiviral therapy in chronic hepatitis C: A retrospective cohort study

Abstract

Objective: To evaluate the effectiveness of direct-acting antivirals (DAAs) in patients with chronic hepatitis C, assess changes in liver function and hepatic fibrosis following treatment, and identify independent predictors of treatment failure.

Methods: This retrospective cohort study included patients who received DAA therapy at Hospital Kuala Lumpur between January 2020 and December 2023. Sustained virologic response (SVR) was assessed at least 12 weeks post-treatment by reverse transcription-polymerase chain reaction for hepatitis C virus (HCV) RNA. Demographic, clinical, and laboratory data were collected and analyzed. Multiple logistic regression analysis was performed to identify independent predictors of treatment failure.

Results: A total of 335 patients in the study. The overall SVR rate was 89%. After achieving SVR, significant improvements were observed in liver enzyme levels and non-invasive liver fibrosis scores, whereas the overall Model for End-Stage Liver Disease (MELD) scores remained unchanged. Significant independent predictors of treatment failure included non-compliance with DAA therapy [adjusted odds ratio (aOR) 68.3; 95% confidence interval (95% CI) 16.3-285.0; P<0.001], treatment with sofosbuvir/velpatasvir (aOR 6.1; 95% CI 1.4-26.5; P=0.015), MELD score of 10-15 (aOR 4.6; 95% CI 1.1-18.2; P=0.031), HCV genotype 3 infection (aOR 4.5; 95% CI 1.1-17.6; P=0.031), and elevated serum total bilirubin level (aOR 1.1; 95% CI 1.0-1.1; P=0.003).

Conclusions: DAA therapy yielded a high SVR rate, and treatment failure was strongly associated with non-adherence to therapy and advanced liver disease. These findings underscore the necessity of adherence support, early diagnosis, and individualized clinical management to optimize treatment outcomes in patients with chronic hepatitis C.

Keywords

Chronic hepatitis C / Direct-acting antiviral agent / Liver function / Cirrhosis / Treatment compliance / Hepatitis elimination

Conflict of interest statement

The authors have no competing interests to declare that are relevant to the content of this article.

Ethical statement

Ethical approval was waived by the National Medical Research Register, the Medical Research and Ethics Committee at the National Institute of Health Malaysia [NMRR ID-23-01664-VNC (IIR)] in view of the retrospective nature of the study and all the procedures being performed were part of the routine care. The site of study, the Clinical Research Centre of Hospital Kuala Lumpur (CRCHKL-2023-07-164) approved this study.

Data availability

The datasets generated during and/or analysed during the current study are not publicly available due to reasons of sensitivity but are available from the corresponding author on reasonable request.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Authors’ contributions

NBH, NIKR, NMT, MM, NZ, ZS and SNM contributed to the study concept; NBH and NIKR were responsible for data acquisition and statistical analysis; NBH, NIKR, NMT, MM, NZ, ZS and SNM drafted the initial manuscript; NMT, MM, NZ, ZS and SNM provided critical review and expert opinion for the manuscript; NBH and SNM take responsibility for the integrity of the work as a whole. All authors have reviewed and approved the final version of the manuscript.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Edited by Pan Y, Lei Y, Zhang Q

Acknowledgments

I would like to express my sincere gratitude to the Pathology

Department at Hospital Kuala Lumpur and all the staff in the Microbiology Unit for providing me with the opportunity and support to conduct this study. I am also grateful to Mrs. Hasnah from the Institute of Medical Research for her guidance on biostatistics and Dr Yau Weng Keong, the Head of the Medical Department at Hospital Kuala Lumpur, for approving the study involving patients suffering from chronic hepatitis C.

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