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Drug Resistance Profile and Clinical Features for Hepatitis C Patients Experiencing DAA Failure in Taiwan

Chun-Ming Hong1, You-Yu Lin2, Chun-Jen Liu2,3

  • 1Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10022, Taiwan.

Viruses
|November 27, 2021
PubMed

Insights

Hepatitis C treatment failures in Taiwan were due to poor adherence and specific drug resistance mutations. Some cases may be reinfections, highlighting unique resistance profiles in Taiwan.

Area of Science:

  • Hepatology
  • Virology
  • Pharmacogenomics

Background:

  • Taiwan faces a significant burden of chronic hepatitis C, with 4% seropositive for anti-HCV antibodies and 70% with HCV RNA.
  • National health insurance in Taiwan now covers genotype-specific and pangenotype direct-acting antivirals (DAAs) to combat this.
  • Despite high success rates (97% SVR12), a small percentage of patients do not clear HCV after DAA treatment.

Purpose of the Study:

  • To investigate the causes of direct-acting antiviral (DAA) treatment failure in Taiwanese patients with hepatitis C virus (HCV).
  • To characterize the resistance-associated substitutions (RASs) and genetic profiles of HCV in DAA failure cases.
  • To compare virologic findings with clinical adherence data.

Main Methods:

  • A multi-center clinical and virologic study enrolled 147 patients who failed DAA therapy.
  • Population sequencing and whole genome sequencing (WGS) were used to identify RASs in HCV NS3/4A, NS5A, and NS5B genes.
  • Clinical adherence and HCV genotype consistency were assessed.

Main Results:

  • Poor patient adherence was a significant clinical cause of DAA failure.
  • Common RASs identified included NS5A-L31, NS5A-Y93, and NS5B-C316 for genotype-specific DAAs, and NS5A-L31, NS5A-A/Q/R30, and NS5A-Y93 for pangenotype DAAs.
  • Whole genome sequencing revealed novel amino acid changes, and 12 cases suggested reinfection due to inconsistent HCV genotypes.

Conclusions:

  • The study identified key virologic and clinical factors contributing to DAA failure in Taiwan.
  • The identified drug resistance profiles differ from those reported in other countries.
  • Findings underscore the importance of adherence monitoring and understanding specific RASs for optimizing HCV treatment strategies in Taiwan.

Keywords:
Taiwanchronic hepatitis Cdirect-acting antiviral agentresistance-associated substitutiontreatment failurewhole genome sequencing

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