Telaprevir‐based triple therapy in liver transplant patients with hepatitis C virus: A 12‐week pilot study providing safety and efficacy data

Abstract

After liver transplantation (LT), the management of recurrent hepatitis C virus (HCV) infections still remains a major challenge. In HCV genotype 1 patients not undergoing transplantation, the introduction of protease inhibitor (PI)-based regimens has increased the sustained virological response rate significantly. This pilot study investigated both the safety and efficacy of telaprevir (TVR)-based triple therapy in HCV-infected LT patients with a special emphasis on drug-drug interactions between immunosuppressants and PIs. Safety and efficacy data were gathered for 12 weeks for 9 HCV-infected LT patients who were treated with a combination of TVR, pegylated interferon, and ribavirin (RBV) in parallel with immunosuppressive drugs such as tacrolimus (TAC; n ¼ 4), cyclosporine A (CSA; n ¼ 4), and sirolimus (SIR; n ¼ 1). Seven of the transplant patients completed the 12 weeks of triple therapy. At week 4, 4 of the patients were found to be HCV RNA-negative, and importantly, 8 were found to be negative at week 12. During the 12-week course of triple therapy, short-term measurements of immunosuppressant trough levels required individual dose reductions in all patients (CSA, 2.5-fold; SIR, 7-fold; and TAC, 22-fold). Furthermore, two-thirds of the patients exhibited hematological side effects requiring RBV dose reductions, the administration of erythropoietin, or even blood transfusions. In conclusion, this pilot study provides evidence showing that TVR-based triple therapy is effective within the first 4 to 12 weeks in LT patients suffering from HCV genotype 1 recurrence, and it also provides evidence showing that drug-drug interactions between TVR and immunosuppressants can be handled appropriately through the close monitoring of trough levels and adequate dosage adjustments.

Telaprevir-based triple therapy for hepatitis C null responders among living donor liver transplant recipients

“…In contrast to several Western reports of the triple therapy demonstrating moderate success for genotype 1 recurrent hepatitis C after DDLT (3,15,16), the present results were discouraging, with an end-of-treatment response rate of only 25% (2/8). It is important to note, however, that all eight recipients indicated for the triple therapy in our study had been resistant to standard dual treatment with PEG-IFN and RBV.…”

“…In the present study, however, only 25% (2/8) of patients achieved HCV-negative status at the end of therapy. Accumulating reports from Western countries in a DDLT setting suggest the efficacy of triple therapy for recurrent hepatitis C with genotype 1b (3,15,16), but the present results demonstrated dismal results for non-responders to standard dual therapy. Documented drug-drug interactions with protease inhibitors have raised concerns about the safety of protease inhibitors in the post-transplant setting.…”

“…It is important to note, however, that all eight recipients indicated for the triple therapy in our study had been resistant to standard dual treatment with PEG-IFN and RBV. In the aforementioned Western reports (3,15,16), triple therapy was used as the initial antiviral treatment for recurrent disease after liver transplantation. Unlike this report, Ikegami and colleagues reported that 82% of patients achieved SVR after LDLT, however, 18% (2/11) of patients did not have previous IFN treatment history (5).…”

“…Several preliminary reports regarding triple therapy for deceased donor liver transplantation (DDLT) in Western countries were recently published (3,4). However, efficacy and safety was not well describe in a living donor liver transplant (LDLT) setting in an Japanese population (5).…”

Boceprevir-based triple therapy for belgian liver transplant patients infected with hepatitis C virus: A preliminary experience

“…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.…”