title: New hepatitis C virus therapies: drug classes and metabolism, drug interactions relevant in the transplant settings, drug options in decompensated cirrhosis, and drug options in end-stage renal disease.
abstract: OBJECTIVE
  This article will review the new direct acting antiviral agent (DAA) drug classes for the treatment of hepatitis C, how they are combined and the relevant drug-drug interactions in the postliver transplant setting. Treatment options for chronic hepatitis C in patients with decompensated cirrhosis and end-stage renal disease will also be discussed.
  
  
  RESULTS
  The availability of new drug classes has increased the treatment options in patients with hepatitis C in the post-transplant settings. Clinical trials have concluded that sofosbuvir (SOF) with ledipasvir (LDV) may be safely administered with calcineurin inhibitors (tacrolimus, cyclosporine) and rapamycin inhibitors (sirolimus, everolimus). Similarly, paritaprevir/ritonavir, ombitasvir, and dasabuvir may be administered with tacrolimus and cyclosporine though appropriate dose adjustments must be made to the calcineurin inhibitors. In those with decompensated Childs B/C cirrhosis, SOF, SOF and LDV, as well as daclatasvir may be given without dose adjustment. In renal impairment, all DAAs may be used safely down to a glomerular filteration rate (GFR) of 30 ml/min. Simeprevir, paritaprevir, ombitasvir, and dasabuvir may be given for those down to GFR of 15 ml/min. Finally, daclatasvir may be given without dose administration change.
  
  
  CONCLUSIONS
  In summary, DAAs have better tolerability and greater efficacy than interferon-based therapy post-transplant. Drug-drug interactions must be carefully assessed when these newer agents are used for therapy in the postliver transplant settings. Thus far, dose adjustments for DAAs have not been required in chronic kidney disease though data are incomplete in those with severe chronic kidney disease (CKD) or on dialysis. Hepatitis C treatment in those with decompensated cirrhosis results in impaired hepatic metabolism that may affect DAA levels, and clinicians should carefully choose treatment options for Childs B and C cirrhotic patients.
authors.affiliation: aDepartment of Medicine, Division of Gastroenterology/Hepatology bDepartment of Medicine, Division of General Internal Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Paul Y
authors.initials: PY
authors.lastname: Kwo
authors.forename: Maaz B
authors.initials: MB
authors.lastname: Badshah
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism / Q000627:therapeutic use*; D004347:Drug Interactions; D016174:Hepacivirus; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications*; D008103:Liver Cirrhosis / Q000209:etiology*; D016031:Liver Transplantation
chemical_list: D000998:Antiviral Agents