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Objectives: The aim of this multicenter retrospective study was to investigate safety and efficacy of direct acting antiviral (DAA) treatment in the rare subgroup of patients with HCV/HIV-coinfection and advanced liver cirrhosis on the liver transplant waiting list or after liver transplantation, respectively., Methods: When contacting 54 German liver centers (including all 23 German liver transplant centers), 12 HCV/HIV-coinfected patients on antiretroviral combination therapy were reported having received additional DAA therapy while being on the waiting list for liver transplantation (patient characteristics: Child-Pugh A (n = 6), B (n = 5), C (n = 1); MELD range 7-21; HCC (n = 2); HCV genotype 1a (n = 8), 1b (n = 2), 4 (n = 2)). Furthermore, 2 HCV/HIV-coinfected patients were denoted having received DAA therapy after liver transplantation (characteristics: HCV genotype 1a (n = 1), 4 (n = 1))., Results: Applied DAA regimens were SOF/DAC (n = 7), SOF/LDV/RBV (n = 3), SOF/RBV (n = 3), PTV/r/OBV/DSV (n = 1), or PTV/r/OBV/DSV/RBV (n = 1), respectively. All patients achieved SVR 12, in the end. In one patient, HCV relapse occurred after 24 weeks of SOF/DAC therapy; subsequent treatment with 12 weeks PTV/r/OBV/DSV achieved SVR 12. One patient underwent liver transplantation while on DAA treatment. Analysis of liver function revealed either stable parameters or even significant improvement during DAA therapy and in follow-up. MELD scores were found to improve in 9/13 therapies in patients on the waiting list for liver transplantation; in only 2 patients a moderate increase of MELD scores persisted at the end of follow-up., Conclusion: DAA treatment was safe and highly effective in this nation-wide cohort of patients with HCV/HIV-coinfection awaiting liver transplantation or being transplanted., Competing Interests: The authors have declared that no competing interests exist.

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., (© Georg Thieme Verlag KG Stuttgart · New York.)

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.

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 = 4), cyclosporine A (CSA; n = 4), and sirolimus (SIR; n = 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., (Copyright © 2012 American Association for the Study of Liver Diseases.)