Retreatment efficacy and predictors of ledipasvir plus sofosbuvir to HCV genotype 1 in Japan
Predictors of treatment efficacy with ledipasvir plus sofosbuvir as direct-acting antiviral (DAA) regimen for HCV infection are still unclear. Retreatment efficacy of ledipasvir plus sofosbuvir for failures to prior DAA regimens, including NS5A inhibitors, are also unknown because resistance-associated variants (RAVs) in NS5A have been shown to persist up to the long-term of post-treatment. One hundred seventy-five patients with chronic HCV genotype 1 infection, without decompensated liver cirrhosis and hepatocellular carcinoma, were evaluated SVR12 by ledipasvir 90mg plus sofosbuvir 400mg once-daily for 12 weeks. Overall, SVR12 were 92%, based on intention to treat analysis. In failures to daclatasvir plus asunaprevir, SVR12 were 71%. The study using ultra-deep sequencing showed that ledipasvir plus sofosbuvir was effective to one case of failures to daclatasvir plus asunaprevir with multidrug RAVs (triple mutation in NS3-D168/NS5A-L31/NS5A-Y93). Multivariate analysis identified FIB4 index (<3.25), IL28B rs8099917 (TT type), and NS5A-L31 (Wild type) as significant determinants of SVR12. SVR12 rates in patients with three factors of poor response (RAVs Positive, IL28B non-TT, and FIB4 index ≥3.25) simultaneously were significantly lower than those of the other patients. Prediction of response to therapy based on combination of three predictors had high sensitivity and positive predictive values. In conclusions, this study indicated the favorable efficacy of ledipasvir plus sofosbuvir for HCV genotype 1 infection, including multidrug RAVs in Japan. Treatment efficacy could be predicted by the combination of viral and host factors. J. Med. Virol. 89:284-290, 2017. © 2016 Wiley Periodicals, Inc..
Medienart: |
Artikel |
---|
Erscheinungsjahr: |
2017 |
---|---|
Erschienen: |
2017 |
Enthalten in: |
Zur Gesamtaufnahme - volume:89 |
---|---|
Enthalten in: |
Journal of medical virology - 89(2017), 2, Seite 284-290 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Akuta, Norio [VerfasserIn] |
---|
Links: |
---|
RVK: |
---|
doi: |
10.1002/jmv.24617 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
OLC1990261701 |
---|
LEADER | 01000caa a2200265 4500 | ||
---|---|---|---|
001 | OLC1990261701 | ||
003 | DE-627 | ||
005 | 20230507231647.0 | ||
007 | tu | ||
008 | 170303s2017 xx ||||| 00| ||eng c | ||
024 | 7 | |a 10.1002/jmv.24617 |2 doi | |
028 | 5 | 2 | |a PQ20170301 |
035 | |a (DE-627)OLC1990261701 | ||
035 | |a (DE-599)GBVOLC1990261701 | ||
035 | |a (PRQ)p1577-9357692a28ce3b082fabfa641d5429acd1e7469248d2a03b6f57465ebb108e833 | ||
035 | |a (KEY)0015763520170000089000200284retreatmentefficacyandpredictorsofledipasvirplusso | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
082 | 0 | 4 | |a 610 |q DE-600 |
084 | |a XA 10000 |q AVZ |2 rvk | ||
084 | |a 44.00 |2 bkl | ||
100 | 1 | |a Akuta, Norio |e verfasserin |4 aut | |
245 | 1 | 0 | |a Retreatment efficacy and predictors of ledipasvir plus sofosbuvir to HCV genotype 1 in Japan |
264 | 1 | |c 2017 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
338 | |a Band |b nc |2 rdacarrier | ||
520 | |a Predictors of treatment efficacy with ledipasvir plus sofosbuvir as direct-acting antiviral (DAA) regimen for HCV infection are still unclear. Retreatment efficacy of ledipasvir plus sofosbuvir for failures to prior DAA regimens, including NS5A inhibitors, are also unknown because resistance-associated variants (RAVs) in NS5A have been shown to persist up to the long-term of post-treatment. One hundred seventy-five patients with chronic HCV genotype 1 infection, without decompensated liver cirrhosis and hepatocellular carcinoma, were evaluated SVR12 by ledipasvir 90mg plus sofosbuvir 400mg once-daily for 12 weeks. Overall, SVR12 were 92%, based on intention to treat analysis. In failures to daclatasvir plus asunaprevir, SVR12 were 71%. The study using ultra-deep sequencing showed that ledipasvir plus sofosbuvir was effective to one case of failures to daclatasvir plus asunaprevir with multidrug RAVs (triple mutation in NS3-D168/NS5A-L31/NS5A-Y93). Multivariate analysis identified FIB4 index (<3.25), IL28B rs8099917 (TT type), and NS5A-L31 (Wild type) as significant determinants of SVR12. SVR12 rates in patients with three factors of poor response (RAVs Positive, IL28B non-TT, and FIB4 index ≥3.25) simultaneously were significantly lower than those of the other patients. Prediction of response to therapy based on combination of three predictors had high sensitivity and positive predictive values. In conclusions, this study indicated the favorable efficacy of ledipasvir plus sofosbuvir for HCV genotype 1 infection, including multidrug RAVs in Japan. Treatment efficacy could be predicted by the combination of viral and host factors. J. Med. Virol. 89:284-290, 2017. © 2016 Wiley Periodicals, Inc. | ||
540 | |a Nutzungsrecht: © 2016 Wiley Periodicals, Inc. | ||
650 | 4 | |a ultra‐deep sequencing | |
650 | 4 | |a sofosbuvir | |
650 | 4 | |a FIB4 index | |
650 | 4 | |a ledipasvir | |
650 | 4 | |a direct‐acting antiviral | |
650 | 4 | |a resistance‐associated variants | |
650 | 4 | |a IL28B | |
650 | 4 | |a HCV | |
650 | 4 | |a multidrug resistance | |
650 | 4 | |a Hepatitis | |
650 | 4 | |a Viral infections | |
650 | 4 | |a Antiviral drugs | |
650 | 4 | |a Genotype & phenotype | |
700 | 1 | |a Sezaki, Hitomi |4 oth | |
700 | 1 | |a Suzuki, Fumitaka |4 oth | |
700 | 1 | |a Fujiyama, Shunichiro |4 oth | |
700 | 1 | |a Kawamura, Yusuke |4 oth | |
700 | 1 | |a Hosaka, Tetsuya |4 oth | |
700 | 1 | |a Kobayashi, Masahiro |4 oth | |
700 | 1 | |a Kobayashi, Mariko |4 oth | |
700 | 1 | |a Saitoh, Satoshi |4 oth | |
700 | 1 | |a Suzuki, Yoshiyuki |4 oth | |
700 | 1 | |a Arase, Yasuji |4 oth | |
700 | 1 | |a Ikeda, Kenji |4 oth | |
700 | 1 | |a Kumada, Hiromitsu |4 oth | |
773 | 0 | 8 | |i Enthalten in |t Journal of medical virology |d Hoboken, NJ : Wiley-Liss, 1977 |g 89(2017), 2, Seite 284-290 |w (DE-627)130482439 |w (DE-600)752392-0 |w (DE-576)016070275 |x 0146-6615 |7 nnns |
773 | 1 | 8 | |g volume:89 |g year:2017 |g number:2 |g pages:284-290 |
856 | 4 | 1 | |u http://dx.doi.org/10.1002/jmv.24617 |3 Volltext |
856 | 4 | 2 | |u http://onlinelibrary.wiley.com/doi/10.1002/jmv.24617/abstract |
856 | 4 | 2 | |u http://search.proquest.com/docview/1845028089 |
912 | |a GBV_USEFLAG_A | ||
912 | |a SYSFLAG_A | ||
912 | |a GBV_OLC | ||
912 | |a SSG-OLC-PHA | ||
912 | |a SSG-OLC-DE-84 | ||
912 | |a GBV_ILN_4012 | ||
936 | r | v | |a XA 10000 |
936 | b | k | |a 44.00 |q AVZ |
951 | |a AR | ||
952 | |d 89 |j 2017 |e 2 |h 284-290 |