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Late Relapse after a Sustained Virologic Response at 24 Weeks after Treatment with Daclatasvir and Asunaprevir Combination Therapy for Chronic Hepatitis C Virus Genotype 1b Infection with Liver Cirrhosis.

ABSTRACT: There have been few studies on relapse after a sustained virological response in hepatitis C virus (HCV) patients treated with interferon-free regimens. Thus, the risk of late relapse in patients treated with interferon-free therapy remains unclear. A 67-year-old woman with HCV genotype 1b and liver cirrhosis received oral daclatasvir and asunaprevir. Combination therapy was stopped after 4 weeks because of an episode of encephalopathy. Nonetheless, an HCV polymerase chain reaction at 24 weeks posttreatment was negative. However, HCV ribonucleic acid was detectable at approximately 62 weeks posttreatment. Very late HCV relapses may occur in patients with liver cirrhosis who receive an interferon-free regimen when the treatment period is insufficient.

SUBMITTER: Uojima H

PROVIDER: S-EPMC5919851 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Late Relapse after a Sustained Virologic Response at 24 Weeks after Treatment with Daclatasvir and Asunaprevir Combination Therapy for Chronic Hepatitis C Virus Genotype 1b Infection with Liver Cirrhosis.

Uojima Haruki H Murakami Shuko S Nakatani Seigo S Hidaka Hisashi H Takeuchi Atsuko A Tanaka Yoshiaki Y Inoue Tomoyoshi T Yamane Keiko K Kubota Kousuke K Nakazawa Takahide T Shibuya Akitaka A Tanaka Yasuhito Y Koizumi Wasaburo W

Internal medicine (Tokyo, Japan) 20171208 7

There have been few studies on relapse after a sustained virological response in hepatitis C virus (HCV) patients treated with interferon-free regimens. Thus, the risk of late relapse in patients treated with interferon-free therapy remains unclear. A 67-year-old woman with HCV genotype 1b and liver cirrhosis received oral daclatasvir and asunaprevir. Combination therapy was stopped after 4 weeks because of an episode of encephalopathy. Nonetheless, an HCV polymerase chain reaction at 24 weeks p ...[more]

PMID: 29225269

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Project description:IntroductionOral daclatasvir (DCV; pangenotypic NS5A inhibitor) plus asunaprevir (ASV; NS3 protease inhibitor) is approved in Japan and Korea for treatment of chronic hepatitis C virus (HCV) genotype 1. Response to DCV + ASV is affected by DCV resistance-associated polymorphisms (RAPs) in HCV NS5A. The prevalence and influence of these RAPs on 12-week sustained virologic response (SVR12) to DCV + ASV was evaluated in Asian and non-Asian patients.MethodsData were pooled from 5 national and international studies of patients with HCV genotype 1b (GT-1b) receiving DCV + ASV at their recommended doses. Baseline NS5A RAPs and their effect on SVR12 were assessed overall, in older (≥65 years) patients, patients with cirrhosis, and in patients stratified by baseline HCV RNA or prior treatment experience with interferon-based therapy.ResultsBaseline NS5A sequences were available from 988 patients (374 Japanese; 125 Korean/Taiwanese; 489 from non-Asian countries), 979 of whom were assessed for SVR12. Pretreatment NS5A-L31F/I/M/V and/or NS5A-Y93H polymorphisms were present in 18% of Japanese and 12-13% of non-Japanese patients; these RAPs reduced SVR12 by 54.9% overall (93.9% [787/838] SVR12 when absent, 39.0% [55/141] SVR12 when present), with comparable reductions observed in Asians and non-Asians and across all categories of treatment experience, age, and cirrhosis. RAP-associated SVR12 rates declined with increasing baseline HCV RNA (SVR12 with RAPs: 64.7% [11/17] at 5-6 log10 IU/mL, 29.8% [14/47] at 7-8 log10). Without baseline RAPs, very high SVR12 rates (92-100%) were observed in older patients and patients with cirrhosis irrespective of national origin, with similarly high rates observed among treatment-naïve and interferon-experienced patients and those with high baseline HCV RNA.ConclusionsFollowing DCV + ASV treatment, the SVR12 rates in GT-1b patients without baseline NS5A-L31F/I/M/V and/or NS5A-Y93H polymorphisms were very high (approximately 90-100%), irrespective of age, cirrhosis, prior interferon treatment, or baseline HCV RNA.FundingBristol-Myers Squibb.

Project description:AimTo assess daclatasvir plus asunaprevir (DUAL) in treatment-naïve patients from mainland China, Russia and South Korea with hepatitis C virus (HCV) genotype 1b infection.MethodsPatients were randomly assigned (3:1) to receive 24 wk of treatment with DUAL (daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily) beginning on day 1 of the treatment period (immediate treatment arm) or following 12 wk of matching placebo (placebo-deferred treatment arm). The primary endpoint was a comparison of sustained virologic response at posttreatment week 12 (SVR12) compared with the historical SVR rate for peg-interferon plus ribavirin (70%) among patients in the immediate treatment arm. The first 12 wk of the study were blinded. Safety was assessed in DUAL-treated patients compared with placebo patients during the first 12 wk (double-blind phase), and during 24 wk of DUAL in both arms combined.ResultsIn total, 207 patients were randomly assigned to immediate (n = 155) or placebo-deferred (n = 52) treatment. Most patients were Asian (86%), female (59%) and aged < 65 years (90%). Among them, 13% had cirrhosis, 32% had IL28B non-CC genotypes and 53% had baseline HCV RNA levels of ≥ 6 million IU/mL. Among patients in the immediate treatment arm, SVR12 was achieved by 92% (95% confidence interval: 87.2-96.0), which was significantly higher than the historical comparator rate (70%). SVR12 was largely unaffected by cirrhosis (89%), age ≥ 65 years (92%), male sex (90%), baseline HCV RNA ≥ 6 million (89%) or IL28B non-CC genotypes (96%), although SVR12 was higher among patients without (96%) than among those with (53%) baseline NS5A resistance-associated polymorphisms (at L31 or Y93H). During the double-blind phase, aminotransferase elevations were more common among placebo recipients than among patients receiving DUAL. During 24 wk of DUAL therapy (combined arms), the most common adverse events (≥ 10%) were elevated alanine aminotransferase and upper respiratory tract infection; emergent grade 3-4 laboratory abnormalities were infrequently observed, and all grade 3-4 aminotransferase abnormalities (alanine aminotransferase, n = 9; aspartate transaminase, n = 6) reversed within 8-11 d. Two patients discontinued DUAL treatment; one due to aminotransferase elevations, nausea, and jaundice and the other due to a fatal adverse event unrelated to treatment. There were no treatment-related deaths.ConclusionDUAL was well-tolerated during this phase 3 study, and SVR12 with DUAL treatment (92%) exceeded the historical SVR rate for peg-interferon plus ribavirin of 70%.

Dataset Information

Late Relapse after a Sustained Virologic Response at 24 Weeks after Treatment with Daclatasvir and Asunaprevir Combination Therapy for Chronic Hepatitis C Virus Genotype 1b Infection with Liver Cirrhosis.

Publications

Late Relapse after a Sustained Virologic Response at 24 Weeks after Treatment with Daclatasvir and Asunaprevir Combination Therapy for Chronic Hepatitis C Virus Genotype 1b Infection with Liver Cirrhosis.

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