title: Aplastic Anemia and Severe Myelosuppression with Boceprevir or Simeprevir-Containing Hepatitis C Virus Treatment.
abstract: The addition of the new protease inhibitors (PIs) to peg-interferon (IFN) and ribavirin (RBV), approved for chronic hepatitis C, has clearly improved sustained virological response (SVR) rates although several adverse events have been reported with this regimens, including mild hematological toxicity. Moreover, severe pancytopenia and aplastic anemia during triple therapy with telaprevir has recently been described in seven patients. We report here two cases of severe agranulocytosis/aplastic anemia using boceprevir or simeprevir in interferon-based combination and 2 additional cases of severe myelosupression in IFN-free therapy with sofosbuvir and simeprevir plus RBV. Our observations suggest that PIs could have a sort of class-effect in developing severe hematologic toxicity or, at least, an additive interaction with other potentially myelotoxic agents such as IFN or RBV that are used in the classical regimens against HCV. Unfortunately, the mechanisms behind this phenomenon are currently unknown. In conclusion, given the lifethreatening character of these complications, close monitoring is mandatory in patients under PIs based therapy to promptly detect serious hematological toxicities and to carefully evaluate treatment discontinuation. Prospective studies assessing the usefulness of RBV in the era of new IFN-free combinations are needed.
authors.affiliation: Department of Clinical Hematology, Hospital del Mar, Barcelona, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Senín
authors.affiliation: Liver Unit, Gastroenterology Department, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Broquetas
authors.affiliation: Liver Unit, Gastroenterology Department, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Cañete
authors.affiliation: Liver Unit, Hospital Clinic, IDIBAPS, CIBERehd, Barcelona, Spain.
authors.forename: Sabela
authors.initials: S
authors.lastname: Lens
authors.affiliation: Liver Unit, Hospital Clinic, IDIBAPS, CIBERehd, Barcelona, Spain.
authors.forename: María-Carlota
authors.initials: MC
authors.lastname: Londoño
authors.affiliation: Department of Clinical Hematology, Hospital del Mar, Barcelona, Spain.
authors.forename: Mariana
authors.initials: M
authors.lastname: Ferraro
authors.affiliation: Liver Unit, Hospital Clinic, IDIBAPS, CIBERehd, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Forns
authors.affiliation: Department of Clinical Hematology, Hospital del Mar, Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Salar
authors.affiliation: Liver Unit, Gastroenterology Department, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Carrión
mesh_terms: D000328:Adult; D000741:Anemia, Aplastic / Q000139:chemically induced* / Q000175:diagnosis / Q000628:therapy; D000998:Antiviral Agents / Q000009:adverse effects*; D001855:Bone Marrow Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000628:therapy; D001856:Bone Marrow Examination; D004359:Drug Therapy, Combination; D017809:Fatal Outcome; D006526:Hepatitis C / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives*; D011480:Protease Inhibitors / Q000009:adverse effects*; D012307:Risk Factors; D012720:Severity of Illness Index; D000069616:Simeprevir / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D011480:Protease Inhibitors; 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; D000069616:Simeprevir
keywords: Anemia; Hepatitis; Toxicity and protease.