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Peer-reviewedCC BY-NC-NDBMC infectious diseases

Prevalence of Y93H resistance-associated substitution in treatment-naïve hepatitis C virus genotype 1b patients: a systematic review and meta-analysis.

12 affiliations
  1. 1Department of Microbiology, Sharda University, Greater, Noida, India.
  2. 2Kookmin University, Seoul, 02707, South Korea.
  3. 3Department of Biotechnology, Graphic Era Deemed University, Dehradun, India.
  4. 4Centre for Promotion of Research, Graphic Era Hill University, Dehradun, India.
  5. 5Department of Surgery, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed-to-be-University), Pimpri, Pune, Maharashtra, 411018, India.
  6. 6School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India.
  7. 7Department of Pharmacology, NIET Pharmacy Institute, Greater, Noida, India.
  8. 8Centre for Research Impact & Outcome, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, 140401, India.
  9. 9Department of Community Medicine, Malla Reddy Institute of Medical Sciences, Hyderabad, India.
  10. 10Saveetha Medical College & Hospital, Saveetha University, Chennai, India.
  11. 11Jawaharlal Nehru Medical College and Global Health Academy, School of Epidemiology and Public Health, Datta Meghe Institute of Higher Education, Wardha, India.
  12. 12University Centre for Research and Development, Chandigarh University, Mohali, Punjab, India. [email protected].

Abstract

Background

Hepatitis C virus (HCV) genotype 1b infection remains a leading cause of chronic liver disease despite advances in direct-acting antivirals (DAAs). Resistance-associated substitutions (RASs) in the non-structural 5 A (NS5A) region, particularly the Y93H mutation, have been associated with reduced antiviral susceptibility and variable treatment outcomes. The global baseline prevalence of this substitution in treatment-naïve populations has not been systematically characterized.Methods

A systematic review and meta-analysis were conducted in accordance with PRISMA 2020 guidelines and registered with PROSPERO. Observational and randomized studies reporting baseline NS5A Y93H prevalence in treatment-naïve HCV genotype 1b patients were identified through PubMed, Embase, and Web of Science. Data were synthesized using a random-effects model, and heterogeneity was quantified by the I² statistic. Sensitivity and publication bias analyses were performed using leave-one-out and DOI plot methods.Results

Nine studies comprising 1,560 treatment-naïve patients from Asia and Europe, were included. The pooled prevalence of Y93H was 12% (95% CI, 6%-20%), with substantial heterogeneity (I² = 82.4%). Sensitivity analyses confirmed result stability, and minor asymmetry in the DOI plot suggested low publication bias.Conclusion

The Y93H substitution is a frequent naturally occurring variant in untreated HCV genotype 1b infection. Despite reduced clinical relevance with pangenotypic DAAs, its persistence warrants continued monitoring. Standardized sequencing and global resistance surveillance remain essential for optimizing treatment strategies and informing antiviral policy.Clinical trial number

Not applicable.

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BibTeX
@article{kakru2026prevalence,
  title = {{Prevalence of Y93H resistance-associated substitution in treatment-naïve hepatitis C virus genotype 1b patients: a systematic review and meta-analysis.}},
  author = {Dilip Kumar Kakru and Do-Youn Lee and Navin Kumar and Rekha Arcot and Sorabh Lakhanpal and Saumya Das and Sanjay Kumar and Sushma Narsing Katkuri and Jeffrin Reneus Paul and Abhay M Gaidhane and Prakasini Satapathy},
  journal = {BMC infectious diseases},
  year = {2026},
  month = jul,
  doi = {10.1186/s12879-026-14091-y},
  url = {https://europepmc.org/article/MED/42902253},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Prevalence of Y93H resistance-associated substitution in treatment-naïve hepatitis C virus genotype 1b patients: a systematic review and meta-analysis.
AU  - Dilip Kumar Kakru
AU  - Do-Youn Lee
AU  - Navin Kumar
AU  - Rekha Arcot
AU  - Sorabh Lakhanpal
AU  - Saumya Das
AU  - Sanjay Kumar
AU  - Sushma Narsing Katkuri
AU  - Jeffrin Reneus Paul
AU  - Abhay M Gaidhane
AU  - Prakasini Satapathy
PY  - 2026
DA  - 2026/07/01
JO  - BMC infectious diseases
DO  - 10.1186/s12879-026-14091-y
UR  - https://europepmc.org/article/MED/42902253
AB  - Background  Hepatitis C virus (HCV) genotype 1b infection remains a leading cause of chronic liver disease despite advances in direct-acting antivirals (DAAs). Resistance-associated substitutions (RASs) in the non-structural 5 A (NS5A) region, particularly the Y93H mutation, have been associated with reduced antiviral susceptibility and variable treatment outcomes. The global baseline prevalence of this substitution in treatment-naïve populations has not been systematically characterized.Methods  A systematic review and meta-analysis were conducted in accordance with PRISMA 2020 guidelines and registered with PROSPERO. Observational and randomized studies reporting baseline NS5A Y93H prevalence in treatment-naïve HCV genotype 1b patients were identified through PubMed, Embase, and Web of Science. Data were synthesized using a random-effects model, and heterogeneity was quantified by the I² statistic. Sensitivity and publication bias analyses were performed using leave-one-out and DOI plot methods.Results  Nine studies comprising 1,560 treatment-naïve patients from Asia and Europe, were included. The pooled prevalence of Y93H was 12% (95% CI, 6%-20%), with substantial heterogeneity (I² = 82.4%). Sensitivity analyses confirmed result stability, and minor asymmetry in the DOI plot suggested low publication bias.Conclusion  The Y93H substitution is a frequent naturally occurring variant in untreated HCV genotype 1b infection. Despite reduced clinical relevance with pangenotypic DAAs, its persistence warrants continued monitoring. Standardized sequencing and global resistance surveillance remain essential for optimizing treatment strategies and informing antiviral policy.Clinical trial number  Not applicable.
SN  - 1471-2334
ER  -