Abstract
Treatment guidelines differ in their recommendation to determine baseline resistance associated substitutions (RAS) before starting a first-line treatment with direct-acting antivirals (DAAs). Here we analyze the efficacy of DAA treatment with baseline RAS information. We conducted a prospective study involving 23 centers collaborating in the GEHEP-004 DAA resistance cohort. Baseline NS5A and NS3 RASs were studied by Sanger sequencing. After issuing a comprehensive resistance report, the treating physician decided the therapy, duration and ribavirin use. Sustained virological response (SVR12) data are available in 275 patients. Baseline NS5A RAS prevalence was between 4.3% and 26.8% according to genotype, and NS3 RASs prevalence (GT1a) was 6.3%. Overall, SVR12 was 97.8%. Amongst HCV-GT1a patients, 75.0% had >800,000 IU/ml and most of those that started grazoprevir/elbasvir were treated for 12 weeks. In genotype 3, NS5A Y93H was detected in 9 patients. 42.8% of the HCV-GT3 patients that started sofosbuvir/velpatasvir included ribavirin, although only 14.7% carried Y93H. The efficacy of baseline resistance-guided treatment in our cohort has been high across the most prevalent HCV genotypes in Spain. The duration of the grazoprevir/elbasvir treatment adhered mostly to AASLD/IDSA recommendations. In cirrhotic patients infected with GT-3 there has been a high use of ribavirin.
Highlights
Hepatitis C infection is a leading cause of liver diseases, liver cirrhosis, and hepatocellular carcinoma
Direct Acting Antiviral (DAA) combinations that are currently recommended as first line treatment of HCV infected patients allow achieving high sustained virological response (SVR) rates (>90–95%) for all HCV genotypes [2]
Most of the patients were infected with HCV GT-1a (n = 223; 43.2%), followed by 141 patients with HCV GT-3 infection (27.3%), 82 patients with HCV GT-1b infection
Summary
Hepatitis C infection is a leading cause of liver diseases, liver cirrhosis, and hepatocellular carcinoma. As of 2015, the Polaris Observatory estimated that, globally, about 71 million of individuals have viraemic HCV infections and need antiviral treatment [1]. Direct Acting Antiviral (DAA) combinations that are currently recommended as first line treatment of HCV infected patients allow achieving high sustained virological response (SVR) rates (>90–95%) for all HCV genotypes [2]. HCV genotype, liver disease severity and previous treatment experience are still considered key factors to select first line treatment regimens by international treatment guidelines [3,4]. HCV GT-1, GT-2, and GT-3 are the most prevalent genotypes [9]. In contrast to the great amount of information on HCV genotype distribution, little information is known about the prevalence of resistance associated substitutions (RAS) in the different genotypes. Most data come from the retrospective analysis of pooled phase II and III clinical trials including patients with HCV GT-1 [11,12] and HCV GT-3 [13,14]
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