title: Hepatitis C virus treatment and liver transplantation in the era of new antiviral therapies.
abstract: OBJECTIVE
  The new standard-of-care treatment for genotype 1 hepatitis C virus infection is a combination of PEG-interferon (PEG-IFN), ribavirin (RBV) and a protease inhibitor - telaprevir or boceprevir. As triple therapy is not yet approved for use in decompensated cirrhotics and liver transplant recipients, we examine the efficacy and safety of PEG-IFN, RBV and protease inhibitors in nontransplant populations to inform the current and future treatment paradigms for transplant candidates and recipients.
  
  
  RESULTS
  Protease inhibitor-based triple therapy is more efficacious than PEG-IFN and RBV in nontransplant genotype 1 patients, so sustained virologic response rates are predicted to be higher in waitlisted candidates and transplant recipients treated with protease inhibitor-triple therapy. Because of the need to use a backbone of PEG-IFN and RBV, tolerability of therapy will remain a major challenge. Anemia, a well recognized side-effect with PEG-IFN and RBV, will be especially common with protease inhibitor-triple therapy. Both protease inhibitors can modify the levels of drugs metabolized by the CYP3A/4 pathway, and in posttransplant patients, the protease inhibitors increase the levels of cyclosporine and tacrolimus, with the magnitude of the drug-drug interactions varying with protease inhibitor and type of calcineurin inhibitor (CNI).
  
  
  CONCLUSIONS
  Given the complexities of treatment, it is best undertaken by experienced clinicians and only after a detailed discussion of risks-benefits with the patient. To maximize the benefit while minimizing risk, only Child-Turcott-Pugh A (CPT-A) cirrhotics should be considered for pretransplant protease inhibitor-triple therapy. For transplant recipients, very close monitoring and adjustment of CNI levels is critical during protease inhibitor-triple therapy. Cytopenias, especially anemia, will require aggressive management.
authors.affiliation: University of California, San Francisco, California, San Francisco, USA.
authors.forename: Varun
authors.initials: V
authors.lastname: Saxena
authors.forename: Norah
authors.initials: N
authors.lastname: Terrault
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000601:surgery / Q000821:virology; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use; D016031:Liver Transplantation; D009842:Oligopeptides / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011392:Proline / Q000031:analogs & derivatives / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D007370:Interferon Type I; D009842:Oligopeptides; D011480:Protease Inhibitors; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline