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NS5A resistance-associated variants undermine the effectiveness of ledipasvir and sofosbuvir for cirrhotic patients infected with HCV genotype 1b.

Abstract：

BACKGROUND:Little real-world cohort data has been reported for Asians who have received interferon-free regimens with sofosbuvir (SOF) for chronic hepatitis C virus (HCV) infection. We evaluated the effectiveness and safety in clinical practice of ledipasvir (LDV) plus SOF for Japanese patients infected with HCV genotype 1. METHODS:This large, multicenter, real-world cohort study consisted of 772 patients treatment-naive or -experienced, with or without compensated cirrhosis, who were treated with LDV (90 mg)/SOF (400 mg) for a fixed 12-week duration. Direct sequence analysis of the NS5A genes (L31 and Y93) was performed at baseline. RESULTS:Almost all (99.6%) were infected with HCV genotype 1b. The overall sustained virological response 12 weeks after the end of treatment (SVR12) rate was 98.8% (763/772). Multivariable logistic regression analysis extracted male (odds ratio [OR] 6.62, p = 0.024), cirrhosis (OR 20.1, p = 0.0054), and baseline NS5A resistance-associated variants (RAVs) (OR 29.3, p = 0.0018) as independently associated with treatment failure. Notably, the SVR12 rate for cirrhosis patients with baseline NS5A RAVs (87.5%, 49/56) was statistically lower than for the other groups. This tendency was found except for patients with prior daclatasvir/asunaprevir failure. All patients with treatment failure had NS5A Y93H at relapse, whether or not they had NS5A RAVs at baseline. Serious adverse effects were very rare, and discontinuation was required for only five (0.6%) patients. CONCLUSIONS:LDV/SOF for HCV genotype 1b was exceptionally effective, however, NS5A RAVs undermined the virological effect for cirrhosis patients. Moreover, LDV/SOF was shown to be safe, irrespective of age or fibrosis status.

journal_name

J Gastroenterol

journal_title

Journal of gastroenterology

authors

Ogawa E,Furusyo N,Nomura H,Dohmen K,Higashi N,Takahashi K,Kawano A,Azuma K,Satoh T,Nakamuta M,Koyanagi T,Kato M,Shimoda S,Kajiwara E,Hayashi J,Kyushu University Liver Disease Study (KULDS) Group.

doi

10.1007/s00535-016-1290-1

subject

Has Abstract

pub_date

2017-07-01 00:00:00

pages

845-854

issue

eissn

0944-1174

issn

1435-5922

pii

10.1007/s00535-016-1290-1

journal_volume

pub_type

杂志文章,多中心研究

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NS5A resistance-associated variants undermine the effectiveness of ledipasvir and sofosbuvir for cirrhotic patients infected with HCV genotype 1b.