To the Editor:
According to the American Association for the Study of Liver Diseases guidelines, the optimal therapy for genotype 1 chronic hepatitis C virus (HCV) infection is the use of boceprevir or telaprevir in combination with pegylated interferon alpha (Peg-IFN-α) and ribavirin (RBV). However, treatment failure is often associated with the presence of HCV mutations that reduce sensitivity to telaprevir or boceprevir. Currently, there is no available therapeutic option in this situation.
We report on the case of a Caucasian 42-year-old man with chronic HCV infection who relapsed after telaprevir-based triple therapy and who was retreated with dual therapy. At admission in our department in May 2005, physical examination was normal, except for overweight (body mass index: 27.5 kg/m2). All blood samples were normal, except for the aminotransferase level—at 1.5 times the upper normal limit. Virus genotype was 1b, and serum HCV RNA was quantified at 6,086,220 IU/mL (6.78 log) (COBAS TaqMan HCV/HPS assay [version 1.0]). All other causes of chronic liver disease were excluded. Liver biopsy showed a METAVIR score of A1F1. In November 2006, the patient entered a protocol of antiviral therapy, combining Peg-IFN-α-2a (180 μg/week), RBV (1,000 mg/day), and telaprevir (750 mg three times every 24 hours) for a total duration of 12 weeks. At initiation, viral load was of 11,900,000 IU/mL and became undetectable (<30 IU/mL; COBAS TaqMan) from day 15 until end of treatement. No major side effect or dosage reduction were noted. However, at week 12 after treatment discontinuation, in May 2007, the patient relapsed, with a viral load at 136,000 IU/mL. Retrospective viral sequencing analysis showed an R155T mutation. In June 2007, we decided to retreat the patient with a “classical” combination of Peg-IFN-α-2a (180 μg/week) and RBV (1,000 mg/day) for 48 weeks. Under this regimen, viral load decreased from 1,070,038 IU/mL (6.03 log) at initiation to 158 IU/mL (2.20 log) at week 4 and became undetectable (<43 IU/mL; COBAS TaqMan) at week 12. The undetectability of viral load persisted during the whole duration of treatment and 6 months after its discontinuation. Currently, viral load is still undetectable, and noninvasive serum markers suggest a METAVIR score of A0F0. Interleukin (IL)28B genotype (rs12979860), retrospectively assessed, was C/T.
In this case report, we show, for the first time, the efficacy of dual therapy with Peg-IFN/RBV in a patient who failed to respond to telaprevir-based triple therapy, despite the presence of a telaprevir-resistant variant. Because of cross-resistance between telaprevir and boceprevir, retreatment with triple therapy was not an option. A previous Japanese study has shown efficiency of Peg-IFN/RBV in patients with a resistant variant secondary to telaprevir monotherapy. As expected, the telaprevir-resistant variant (R155T) was eliminated with Peg-IFN/RBV in our patient. Relapse subsequent to the first 12-week course of telaprevir-based triple therapy might be explained by the short duration of treatment, together with unfavorable IL28B genotype. Retreatment with a 48-week course of Peg-IFN/RBV was able to achieve SVR, suggesting therapeutic insufficiency during the first course of treatment. Therefore, pending new molecules, retreatment with a reinforced regimen of Peg-IFN/RBV could be a therapeutic option in genotype 1–naïve patients who failed to achieve sustained virological response with telaprevir-based triple therapy.
OlivierChazouillères M.D., Ph.D.
AP-HP, Hôpital Saint-Antoine, Service d'Hépatologie, Paris, France
University Pierre and Marie Curie Paris 6, UMR_S938, Paris, France