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TO THE EDITORS:

The management of recurrent hepatitis C virus (HCV) infections remains a major challenge after liver transplantation because sustained virological response rates are generally less favorable than those in nontransplant settings.[1] Protease inhibitor–based regimens improve the virological response in nontransplant patients with HCV genotype 1. In a previous issue of Liver Transplantation, Werner et al.[2] demonstrated the safety and efficacy of telaprevir-based triple therapy in liver transplant patients with HCV. Boceprevir with a calcineurin inhibitor (CNI) seems to require a lower dose reduction than telaprevir.[3] Here we report the Belgian experience with boceprevir-based triple therapy after liver transplantation. The safety and efficacy of boceprevir treatment in combination with pegylated interferon and ribavirin were investigated in 7 liver transplant patients with recurrent HCV genotype 1 (3 men and 4 women with a mean age of 53 ± 10.4 years). Two patients had cholestatic hepatitis, and 5 had chronic hepatitis with F1 (n = 1), F2 (n = 1), F3 (n = 1), or F4 fibrosis (n = 2) according to the METAVIR system. The median time between liver transplantation and HCV treatment initiation was 249 days (range = 47-2411 days). The median follow-up period was 33 weeks (range = 15.86-54.43 weeks). All patients had achieved a steady state of immunosuppressive drug use before boceprevir initiation. Because of drug interactions, the immunosuppressant treatment was reduced in all but 1 patient, and this led to stability of the CNI trough blood concentration after boceprevir initiation, as shown in Table 1. In 1 patient, the serum creatinine level increased, although the CNI levels always remained in the therapeutic range. All patients required a ribavirin dose reduction because of anemia; in addition, 6 patients received blood transfusions, 4 patients were administered erythropoietin, and boceprevir was ceased for 1 patient after 8 weeks of triple therapy. The median HCV viral loads at the beginning of HCV treatment and at the time of boceprevir initiation were 7.54 × 106 IU/mL (range = 1.07 × 106 to 7 × 107 IU/mL) and 5.85 × 105 IU/mL (range = 2.59 × 104 to 5.5 × 107 IU/mL), respectively. After 8 weeks of triple therapy, 5 patients had HCV viral loads less than 30 IU/mL, and they remained negative until the end of follow-up; 1 patient was a nonresponder with a viral load of 402 IU/mL; and 1 patient stopped treatment because of severe anemia and thrombocytopenia at week 4. These results confirm the feasibility of boceprevir-based triple therapy in liver transplant patients. The efficacy results are promising, but close monitoring of immunosuppressive drug levels and hematological side effects is required.

Table 1. Immunosuppressive Regimens, Renal Function, Hemoglobin Levels, and Anemia Management During Boceprevir-Based Therapy
 Patient 1Patient 2Patient 3Patient 4aPatient 5bPatient 6Patient 7
CNITacrolimusTacrolimusCyclosporine A TacrolimusCyclosporine ACyclosporine A
Other immunosuppressionMycophenolate mofetilMycophenolate mofetilMycophenolate mofetilEverolimus and mycophenolate mofetilMycophenolate mofetilMycophenolate mofetilMycophenolate mofetil and steroid
  1. a

    Treatment was stopped at week 4.

  2. b

    Boceprevir was stopped at week 8.

  3. c

    Modification of Diet in Renal Disease.

CNI/everolimus dose (mg/day)       
Week 0621501.751200250
Week 420.55010.585250
Week 810.575 0.7575250
Week 160.750.7575 270250
CNI/everolimus level (ng/mL)       
Week 011.56.91527.42.115970
Week 4Not done4.9628.53.4119295
Week 87.52.3101 7.897109
Week 165.6483 5.355273
Creatinine (mg/dL)/glomerular filtration rate (mL/minute)c       
Week 00.9/>600.9/>600.7/>601.6/491.9/371.1/>600.4/>60
Week 40.9/>601/>600.7/>601.5/521.7/391.3/560.4/>60
Week 80.79/>601/>600.9/>60 1.7/371.5/500.7/>60
Week 160.8/>601.1/560.9/>60 1.6/401.6/450.8/>60
Hemoglobin (g/dL)       
Week 07.1118.99.48.812.79.3
Week 49.19.88.77.288.88.2
Week 810.66.49.3 6.98.210.3
Week 1610.410.47.8 10.99.109.1
Ribavirin dose (mg/day)       
Week 0600800600600400200400
Week 44008006000200200400
Week 8400400600 2000400
Week 16600400400 20000
Blood transfusionYesYesYesYesYesNoYes
Erythropoietin administrationYesYesYesNoYesNoNo
  • Delphine Degre, M.D.1

  • Isabelle Colle, M.D., Ph.D.2

  • Hans Van Vlierberghe, M.D., Ph.D.2

  • Christophe Moreno, M.D., Ph.D.1

  • 1Department of Gastroenterology, Hepatopancreatology, and Digestive OncologyErasme HospitalUniversité Libre de BruxellesBrussels, Belgium

  • 2Department of HepatogastroenterologyGhent University HospitalGhent, Belgium

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