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.

AIMTo gather data on the antiviral efficacy and safety of second generation direct acting antiviral (DAA) treatment with respect to sustained virological response (SVR) 12 wk after conclusion of treatment, and to determine predictors of SVR12 in this setting.METHODSTwo hundred and sixty patients treated with SOF combination partners PR (n = 51), R (n = 10), SMV (n = 30), DCV (n = 81), LDV (n = 73), or 3D (n = 15). 144/260 were pre-treated, 89/260 had liver cirrhosis, 56/260 had portal hypertension with platelets < 100/nL, 25/260 had a MELD score ≥ 10 and 17/260 were post-liver transplantation patients. 194/260 had HCV GT1, 44/260 HCV GT3.RESULTSTwo hundred and forty/256 (93.7%) patients achieved SVR12 (mITT); 4/260 were lost to follow-up. SVR12 rates for subgroups were: 92% for SOF/DCV, 93% for each SOF/SMV, SOF/PR, 94% for SOF/LDV, 100% for 3D, 94% for pretreated, 87% for liver cirrhosis, 82% for patients with platelets < 100/nL, 88% post-liver transplantation, 95% for GT1a, 93% for GT1b, 90% for GT3, 100% for GT2, 4, and 6. 12 patients suffered from relapse, 6 prematurely discontinued treatment, of which 4 died. Negative predictors of SVR12 were a platelet count < 100/nL, MELD score ≥ 10 (P < 0.0001), liver cirrhosis (P = 0.005) at baseline. In Interferon-free treatment GT3 had significantly lower SVR rates than GT1 (P = 0.016). Side effects were mild.CONCLUSIONExcellent SVR12 rates and the favorable side-effect profile of DAA-combination therapy can be well translated into “real-world”. Patients with advanced liver disease, signs of portal hypertension, especially with platelets < 100/nL and patients with GT3 are in special need for further research efforts to overcome comparatively higher rates of virological failure.

Recurrent HCV infection post-liver transplantation (post-LT) is still a major challenge in the treatment of hepatitis C virus (HCV) infection. In this retrospective analysis we gathered data about treatment response and safety of all 14 post-LT patients who were treated between 2011 and 2013 at our centre with a telaprevir (TVR)-based triple therapy. Seven out of 14 patients completed the full treatment course of 48 weeks. Five patients achieved a SVR 24, while 3 additional HCV RNA-negative patients are still in follow-up (end of treatment, SVR 12 and 22). Four patients discontinued treatment prematurely due to side effects. A virological non-response at TW 4 was seen in 1 patient. Virological breakthrough was observed in 2 patients at TW 16 and 28, respectively; 1 patient displayed a virological relapse after the end of treatment (EOT). Patients with a complicated course post-LT accumulated most of the severe side effects, largely infections. One patient with cholestatic hepatitis died 11 weeks after discontinuation of treatment due to progressive graft failure. In conclusion, TVR-based triple therapy in post-LT patients reveals an acceptable antiviral efficacy. Unfortunately, severe side effects are frequent and often require therapeutic interventions. Therefore, with the approval of less straining DAA like sofosbuvir in sight, TVR-based triple therapy in post-LT patients should be, if possible avoided.

Since 2011, telaprevir (TVR)-based triple therapy is the new treatment standard for hepatitis C genotype 1 virus infection. The aim of our retrospective interim analysis encompassing the first 24 weeks on TVR-based triple therapy was to assess 'real-life' antiviral efficacy and side effects in a large single-centre cohort, both in comparison with the data obtained in large prospective clinical trials. In total, we treated 102 patients: 24 treatment-na€ ıve patients, 58 patients pretreated with PEG-IFN/RBV (thereof: 28 with nonresponse, 25 with relapse, five unknown) and 20 patients who previously had received nonpegylated interferon. 74 of 102 patients were assigned with HCV genotype 1b; 34 of 102 patients were treated in the context of liver cirrhosis. 72 of 102 patients have reached treatment week 24 (mean treatment duration 31 weeks). In the ITT analysis, overall response rates were at: week 4: 66%; week 12: 85%; and week 24: 78%. So far, 24 patients discontinued treatment prematurely, of those, 10 patients were due to virological failure. Haematological side effects were frequent (40% anaemia), as were 'flu-like' symptoms (94%), rash (65%) and pruritus (79%). According to our interim ITT analysis encompassing up to 24 weeks of TVR-based triple therapy, our 'real-life' antiviral effects are comparable to the results of large multicentric clinical trials. However, TVR-based triple therapy exhibited a high frequency of side effects requiring multiple therapeutic interventions. Notably, in our 'real-life' cohort, no lethal case was observed so far.

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.