Feasibility of Telaprevir-Based Triple Therapy in Liver Transplant Patients with Hepatitis C Virus: SVR 24 Results

Abstract

Management of recurrent Hepatitis C virus (HCV) infection following liver transplantation remains a major challenge. In non-transplanted HCV genotype 1 patients, the introduction of protease inhibitor-based regimens has significantly increased the rate of sustained virological response. In this follow-up study, on the first published cohort of post-liver transplant patients treated with telaprevir-based triple therapy, we investigated both efficacy and safety data in follow-up to 24 weeks (SVR 24) after end of treatment (EOT). SVR 24 efficacy and safety data from 9 liver transplant HCV patients being treated with telaprevir, pegylated interferon, and ribavirin, showed 5 of the transplanted patients accomplished the full duration of the 48 week triple therapy. Notable were the 4 patients found to be HCV RNA-negative at week 4, and 8 patients at week 12. Upon EOT, at week 48, 6 patients were HCV RNA-negative. Importantly, at follow-up (24 weeks after EOT), a favorable sustained virological response rate was observed in 5 of these patients with HCV RNA remaining negative, including in one patient who discontinued treatment prematurely. Due to side effects, 2 patients discontinued, 2 suffered from virological breakthrough after the telaprevir treatment phase, and 1 patient had a relapse after EOT. Two thirds of patients exhibited hematological side effects requiring ribavirin dose reductions, administration of erythropoetin, or even blood transfusions. This retrospective analysis provides evidence that - with respect to SVR 24 - liver transplant patients suffering from HCV genotype 1 recurrence may benefit from a telaprevir-based triple therapy as this new regimen showed acceptable antiviral efficacy in this small cohort of mostly pre-treated patients. Management of drug-drug interactions is challenging, but feasible. In part severe side effects are frequent during treatment and require therapeutic interventions.

Treatment of Recurrent Genotype 1 Hepatitis C Post-Liver Transplantation: Single Center Experience with Telaprevir-Based Triple Therapy

“…Granulocyte-colony stimulating factor (G-CSF) was given if patients' leukocyte counts were found to be below 1000/µl [26]. The modalities of treatment, on-treatment surveillance, and follow-up are described in detail in our recent publications [19,25].…”

“…However, no episodes of acute rejection occurred and no premature discontinuation was caused by disturbances in trough levels of immunosuppression [19,25]. Fig.…”

“…Looking back on TVR-triple therapy, demanding side effects are the hallmark of this treatment regimen at least in "difficult-totreat" groups of patients. Presumably, side effects represent the downside of the strong antiviral potency of TVR-based triple therapy both in post-LT and non-LT patients [19,25,26], being considerably more pronounced in the post-LT group of patients. Surely, the major side effect is hematological toxicity, with severe anemia (hemoglobin < 8.5 g/dL) in almost all post-LT patients (Eleven out of 14), according to other post-LT experiences [21,23,24].…”

Management of Hepatitis C Before and After Liver Transplantation in the Era of Rapidly Evolving Therapeutic Advances

“…Another smaller series reported a SVR rate of 56% (5/9) with TVR-based triple therapy for LT recipients with recurrent HCV (most of them were previously treated with PEG-IFN/RBV). 58 There is limited data on the interaction between DAA and mammalian target of rapamycin (mTOR) inhibitors. Recognizing that sirolimus carries a black box warning for use in LT, 59 it may be sensible to avoid this agent altogether in patients receiving TVR or BOC.…”

“…60 Taken together, DDA-based therapy is feasible for LT recipients with severe HCV recurrence. 54,57,58 Higher rates of SVR (more than 50%) can be expected with BOC-and TVRbased therapy, but close monitoring for side effects and immunosuppressive drug levels are warranted. The use of newer protease inhibitors, such as simeprevir, faldeprevir, daclatasvir, and sofosbuvir, will likely be associated with improved SVR rates in LT recipients as well as fewer drug interactions and side effects.…”