Practical management of boceprevir and immunosuppressive therapy in liver transplant recipients with hepatitis C virus recurrence.
Hepatitis C virus (HCV) recurrence is the most important complication in HCV liver transplant patients. Boceprevir with pegylated interferon and ribavirin (PegIFN/RBV) enabled improvement in sustained virological response rates of patients with genotype 1 HCV. Boceprevir interacts with immunosuppressive therapy (IT) by inhibiting the cytochrome P450 3A enzyme. Our aim was to study interactions and assess the safety of boceprevir in the context of HCV recurrence. Boceprevir (800 mg three times a day) initiated after a 4-week lead-in phase was associated with cyclosporine (three patients), tacrolimus (two patients), and everolimus (one patient) in five liver transplant patients with genotype 1 HCV infection who experienced HCV recurrence. The mean follow-up period after HCV therapy was 14.8 ± 3.1 weeks. Estimated oral clearances of IT decreased on average by 50%, requiring reduced dosing regimens. Anemia occurred in all patients, with a mean fall in hemoglobin levels between baseline and week 12 of 3.12 ± 2.27 g/dl. All patients required administration of β-erythropoietin (n = 5), three needed ribavirin dose reduction, and one needed a blood transfusion. A virological response was observed in all patients (mean HCV viral load [HVL] decrease at week 12, 6.64 ± 0.35 log(10) IU/ml). These preliminary results in liver transplant patients with HCV recurrence demonstrate the feasibility and safety of coadministration of boceprevir and IT.
AP-HP, Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France.
Audrey
A
Coilly
Valérie
V
Furlan
Bruno
B
Roche
Caroline
C
Barau
Coralie
C
Noël
Laurence
L
Bonhomme-Faivre
Teresa Maria
TM
Antonini
Anne-Marie
AM
Roque-Afonso
Didier
D
Samuel
Anne-Marie
AM
Taburet
Jean-Charles
JC
Duclos-Vallée
D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use; D019468:Disease Management; D004359:Drug Therapy, Combination; D000068338:Everolimus; D016174:Hepacivirus / Q000187:drug effects* / Q000254:growth & development; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012008:Recurrence; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D016559:Tacrolimus / Q000494:pharmacology / Q000627:therapeutic use; D019562:Viral Load / Q000187:drug effects
D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D016572:Cyclosporine; 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; D000068338:Everolimus; C100416:peginterferon alfa-2a; D020123:Sirolimus; D016559:Tacrolimus