title: The efficacy and safety of direct acting antiviral treatment and clinical significance of drug-drug interactions in elderly patients with chronic hepatitis C virus infection.
abstract: Direct antiviral therapies for chronic hepatitis C virus (HCV) infection have expanded treatment options for neglected patient populations, including elderly patients who are ineligible/intolerant to receive interferon (IFN)-based therapy.
  
  
  
  To investigate the efficacy, tolerability and potential for drug-drug interactions (DDIs) of IFN-free treatment in patients aged ≥65 years in a large real-world cohort.
  
  
  
  A total of 541 patients were treated with different combinations of direct antiviral agents (DAAs: ledipasvir/sofosbuvir ±ribavirin; daclatasvir/sofosbuvir ±ribavirin; paritaprevir/ombitasvir ±dasabuvir ±ribavirin or simeprevir/sofosbuvir ±ribavirin in genotype 1/4, and daclatasvir/sofosbuvir ±ribavirin or sofosbuvir/ribavirin in genotype 2/3). Efficacy, safety and potential DDIs were analysed and compared between patients aged <65 years (n = 404) and patients aged ≥65 years (n = 137) of whom 41 patients were ≥75 years.
  
  
  
  Sustained virological response rates were 98% and 91% in patients aged ≥65 years and <65 years, respectively. Elderly patients took significantly more concomitant medications (79% vs. 51%; P < 0.0001). The number of concomitant drugs per patient was highest in patients ≥65 years with cirrhosis (median, three per patient; range, 0-10). Based on the hep-druginteractions database, the proportion of predicted clinically significant DDIs was significantly higher in elderly patients (54% vs. 28%; P < 0.0001). The number of patients who experienced treatment-associated adverse events was similar between the two age groups (63% vs. 65%; P = n.s.).
  
  
  
  Elderly patients are at increased risk for significant DDIs when treated with DAAs for chronic HCV infection. However, with careful pre-treatment assessment of concomitant medications, on-treatment monitoring or dose-modifications, significant DDIs and associated adverse events can be avoided.
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany. Johannes.Vermehren@kgu.de.
authors.forename: J
authors.initials: J
authors.lastname: Vermehren
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany.
authors.forename: K-H
authors.initials: KH
authors.lastname: Peiffer
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Welsch
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Grammatikos
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany.
authors.forename: M-W
authors.initials: MW
authors.lastname: Welker
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Weiler
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany.
authors.forename: T M
authors.initials: TM
authors.lastname: Welzel
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Sarrazin
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004347:Drug Interactions; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy; D008297:Male; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents