Efficacy and safety of ledipasvir/sofosbuvir with ribavirin in chronic hepatitis C patients who failed daclatasvir/asunaprevir therapy: pilot study
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In Japan, daclatasvir (DCV) and asunaprevir (ASV) therapy was the first IFN-free treatment to be approved, and thousands of patients have since been successfully treated, with an SVR rate of around 90%. The converse, however, is that around 10% of patients fail to achieve viral eradication and must be retreated using a different approach. This study is to evaluate treatment efficacy of ledipasvir/sofosbuvir and ribavirin in patients who failed to respond to DCV and ASV therapy.
Thirty patients were treated with 12 weeks of ledipasvir/sofosbuvir and ribavirin. We evaluated the rate of sustained virological response 12 weeks after the end of treatment (SVR12) and examined the incidence of adverse events during ledipasvir/sofosbuvir and ribavirin treatment. NS5A and NS5B resistance-associated variants (RAVs) in treatment failure cases were examined.
The overall SVR12 rate was 86.7% (26/30). Large decreases in mean log10 HCV RNA levels were observed in patients without cirrhosis, and the SVR12 rate for these patients was 100% (12/12). In cases of cirrhosis, SVR12 rate was 72.2% (13/18). The common factors in treatment failure cases were the presence of liver cirrhosis and both NS5A L31M/I and Y93H RAVs. The frequency of RAVs did not change before and after treatment among patients who relapsed.
Ledipasvir/sofosbuvir with ribavirin is an effective retreatment option for patients with chronic hepatitis C who failed to respond to prior daclatasvir and asunaprevir therapy.
KeywordsDaclatasvir Asunaprevir Ledipasvir/sofosbuvir with ribavirin Retreatment Resistance-associated variants NS5A inhibitor NS5B polymerase inhibitor
The Institute of Physical and Chemical Research
Hepatitis C virus
Sustained virological response
Direct-acting antiviral agents
End of treatment
Serious adverse event
We thank Akemi Sada for clerical assistance, and Tsuyoshi Nagata for preparation of the manuscript. Part of this work was carried out at the Analysis Center of Life Science, Hiroshima University. This study was supported by the Research Program on Hepatitis from Japanese Agency for Medical and development (AMED) Japan (Grant Number16fk0210301h0003).
Compliance with ethical standards
Conflict of interest
K. Chayama has received research grants and consulting fees from Bristol-Myers Squibb, Dainippon Sumitomo Pharma, Mitsubishi Tanabe Pharma, Daiichi Sankyo, Toray Industries, Otsuka Pharmaceutical Company, and GlaxoSmithKline KK. All other authors have no conflicts to report.
This study was supported in part by a Grant-in-Aid for Scientific Research from the Japanese Ministry of Labor and Health and Welfare.
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