ABSTRACT FINAL ID: 1924
TITLE: Favorable efficacy of combination therapy with direct-acting antivirals to elderly aged 70 and older with HCV genotype 1
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This study was supported in part by a Grant-in-Aid from the Ministry of Health, Labor and Welfare, Japan.
BACKGROUND: All-oral combinations with direct-acting antivirals for patients with HCV infection show the favorable efficacy, but treatment efficacy and pretreatment predictors of efficacy for elderly aged 70 and older is unclear. The first aim of this study was to determine treatment efficacy and pretreatment predictors of efficacy, especially in elderly. The second aim was to determine the impact of treatment to AFP levels and Liver Stiffness, that might be useful as one of predictors of early hepatocarcinogenesis in HCV patients without hepatocellular carcinoma.
METHODS: 914 patients, with chronic HCV genotype 1b infection, introduced the regimen of daclatasvir 60 mg once daily plus asunaprevir 100 mg twice daily for 24 weeks. Resistance-associated variants (RAVs) of NS3-D168 and NS5A-L31/Y93 were evaluated using cycling-probe real-time PCR combined with direct sequencing and/or PCR invader assay. Quantitative analysis of NS5A-Y93H mutation more than 20% was evaluated as significant. Liver stiffness levels were evaluated at baseline and at point within 6 months after the stop of treatment. FibroScan 502 was used for measurement with the M-probe and XL-probe.
RESULTS: Sustained virological response (SVR) rates, based on intention to treat analysis, were 87% and 88% in overall patients and elderly aged 70 or more, respectively. SVR rates of patients, without RAVs in NS3 and/or NS5A region by direct sequencing, were 94% and 94% in overall patients and elderly aged 70 or more, respectively. In both groups of overall patients and elderly aged 70 or more, multivariate analysis identified NS5A-Y93H mutation (<20 %), pretreatment (failures to treatment except for triple therapy with simeprevir, or treatment naive), and levels of viremia (<6.0 log IU/ml) as independent pretreatment predictors of SVR. Frequencies of patients with NS3-D168 mutation at baseline, by direct sequencing, in failures to triple therapy with simeprevir (44%) were significantly higher than those of the others (2%). Levels of AFP and Liver Stiffness after the stop of treatment were significantly lower than those at baseline, in both groups of SVR and non SVR.
CONCLUSIONS: All-oral combinations with daclatasvir and asunaprevir achieved the high SVR rates to HCV genotype 1b patients, including the elderly aged 70 and older. Viral factors, including RAVs in NS3 and/or NS5A region, mainly affected poor response. The induction of treatment improved levels of AFP and Liver Stiffness as surrogate marker of hepatocellular carcinoma, regardless of treatment efficacy. Further study should be performed to investigate whether viral eradication in elderly might improve the prognosis.