Daily Low-dose Tacrolimus Is a Safe and Effective Immunosuppressive Regimen During Telaprevir-based Triple Therapy for Hepatitis C Virus Recurrence After Liver Transplant

Papadopoulos-Köhn, A; Achterfeld, Anne; Paul, Andreas; Canbay, Ali; Timm, Jörg; Jochum, Christoph; Gerken, Guido; Herzer, Kerstin

doi:10.1097/tp.0000000000000399

Cited by 7 publications

(8 citation statements)

References 25 publications

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“…First-generation PIs (TLV, BCV) are not only processed by but also inhibit the CYP3A4 isoenzyme, which is involved in the metabolism of most drugs, including the calcineurin inhibitors (CNIs) cyclosporin A (CSA) and tacrolimus (TAC). BCV has been shown to cause a 2.7-fold increase in the area under the curve (AUC) of CSA and a 17-fold increase in the AUC of TAC, whereas TLV causes a 4.6-fold increase in the AUC of CSA and a 70-fold increase in the AUC of TAC [31,32] . Considering the narrow therapeutic range of CSA and TAC, dose adjustments are of imminent importance, and these drugs must be very closely monitored when they are combined with PIs [27,28,33] .…”

Section: Previous Therapeutic Strategiesmentioning

confidence: 99%

Hepatitis C virus reinfection after liver transplant: New chances and new challenges in the era of direct-acting antiviral agents

Herzer

Gerken

2015

WJH

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The first interferon-free regimens have been approved for the treatment of patients with chronic hepatitis C virus (HCV). In the liver transplant (LT) setting, these regimens are expected to have an important effect, because graft loss due to HCV recurrence is a serious problem after LT. The response to the hitherto conventional treatment with pegylated interferon and ribavirin is poor. The significantly better response rates achieved with boceprevir-based and telaprevirbased triple therapy have led to better graft and patient survival rates, but severe drug interactions with immunosuppressants limit the feasibility of this therapy for LT patients. With the approval of sofosbuvir in January 2014, of simeprevir in May 2014, and of daclatasvir in August 2014, three antiviral agents are now available and promise to be applicable without relevant adverse effects or negative interactions with immunosuppressants. Thus, 2014 marks the beginning of a new era of treatment options for HCV recurrence after LT. Although safety and efficacy studies of several interferon-free regimens for patients with HCV recurrence after LT have achieved good preliminary results, reports of clinical experiences with LT patients are scarce. The lack of randomized studies, the small number of enrolled and carefully selected patients, and the heterogeneity of these studies make the results questionable. Real-life experiences are eagerly awaited so that clinicians can estimate the usefulness and the pitfalls of these new regimens. Additionally, the high costs of these agents may limit their accessibility for many patients. The aim of this review is to summarize the current experience with and the expectations of the new direct-acting antiviral agents for LT patients. Core tip: In the liver transplant (LT) setting, graft loss due to hepatitis C virus (HCV) recurrence is a serious problem after LT. The former conventional treatment with pegylated interferon and ribavirin is unsatisfying, due to poor response rates and tolerability. With the first interferon-free regimens that are currently being approved for the treatment of patients with chronic HCV, 2014 marks the beginning of a new era MINIREVIEWSSubmit a

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Section: Previous Therapeutic Strategiesmentioning

confidence: 99%

Hepatitis C virus reinfection after liver transplant: New chances and new challenges in the era of direct-acting antiviral agents

Herzer

Gerken

2015

WJH

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“…The day after stopping TVR, CyA was reinstituted at the dose before TVR-therapy with controls according to TAC. Trough blood concentrations (TBC) ranged from 5 to 7 ng/mL for TAC and from 50 to 80 ng/mL for CyA [16] . Creatinine clearance was estimated using the MDRD formula.…”

Section: Management Of Immunosuppression and Safety Assessmentsmentioning

confidence: 99%

“…All patients recovered completely from all side effects after discontinuation of treatment. Trough blood concentrations of IS were kept stable using a special dosing regimen as described [16] . Frequent controls of TBC were performed.…”

Section: Safetymentioning

confidence: 99%

“…Exclusion criteria for antiviral treatment were evidence of biopsy-proven acute rejection during the past 3 mo or any medical contraindication to treatment with PEG-IFN and RBV that would predict the occurrence of complications during IFN administration, such as platelet count lower than 100000/μL or white blood cell count lower than 2000/μL; clinical signs or laboratory values indicating decompensating liver function; renal insufficiency, with a glomerular filtration rate (GFR) lower than 60 mL/min; and anemia, with a hemoglobin level lower than 10 mg/dL at baseline. Whenever possible, treatment with mycophenolate mofetil and corticosteroids was discontinued before the initiation of antiviral treatment [16] . As limited experience exists in the post-LT setting, patients were thoroughly informed of possible interactions and side effects prior to treatment.…”

Section: Patients Studiedmentioning

confidence: 99%

“…For the assessment of efficacy, viral load was monitored in plasma using the ABBOTT Real Time HCV assay (Abbott Molecular, United States; lower limit of detection 12 IU/mL) at baseline and then at week 1, 2, 3, 4,8,12,16,20,24, 36 and 48. Genotypes were determined using phylogenetic analyses of the core region.…”

Section: Antiviral Treatment Regimenmentioning

confidence: 99%

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Management of telaprevir-based triple therapy for hepatitis C virus recurrence post liver transplant

Herzer¹

2015

WJH

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AIM: To characterize management of telaprevir (TVR)-based triple therapy of hepatitis C virus (HCV) reinfection after liver transplantation (LT). METHODS:We retrospectively analyzed safety and efficacy of telaprevir -based triple therapy in a single center cohort of 19 patients with HCV genotype (GT) 1 recurrence after LT, with respect to factors possibly predicting sustained viral response (SVR) or non-SVR. All patients were treated with TVR, pegylated (PEG) and ribavirine (RBV) for 12 wk followed by a dual phase with PEG/RBV for 12 wk in 7 patients and for 36 wk in 5 patients. RESULTS:In total 11/19 (58%) of patients achieved a sustained response. All (11/11) SVR patients showed a rapid viral response at treatment weeks 4 and 11/14 rapid virological response (RVR) patients achieved SVR. Notably, all (7/7) patients who completed 48 wk of therapy and 80% (4/5) patients who completed Management of telaprevir-based triple therapy for hepatitis C virus recurrence post liver transplant Retrospective Study ORIGINAL ARTICLE24 wk of therapy achieved SVR24. Treatment failure was significantly (P > 0.049) more frequent in GT1a infection (5/7) compared to GT1b (3/12) infection and was associated with emergence of resistance-associated mutations in the NS3 protease domain. Bilirubin level at baseline is also related to SVR (P > 0.030). None of the patients had to discontinue treatment due to side effects.CONCLUSION: RVR, GT and bilirubin are clearly related to achievement of SVR. Providing a thorough patient selection and monitoring, a full course of TVR-based triple therapy in LT patients is feasible and achieves high SVR rates.

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Therapie der Hepatitis C bei Patienten mit Zirrhose sowie vor und nach Lebertransplantation

Herzer

Gerken

2015

Gastroenterologe

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Daily Low-dose Tacrolimus Is a Safe and Effective Immunosuppressive Regimen During Telaprevir-based Triple Therapy for Hepatitis C Virus Recurrence After Liver Transplant

Abstract: In conclusion, substantial dose reduction and daily administration of low doses of TAC compose a safe and efficient immunosuppressive regimen during TVR-based triple therapy.

Cited by 7 publications

References 25 publications

Hepatitis C virus reinfection after liver transplant: New chances and new challenges in the era of direct-acting antiviral agents

Hepatitis C virus reinfection after liver transplant: New chances and new challenges in the era of direct-acting antiviral agents

Management of telaprevir-based triple therapy for hepatitis C virus recurrence post liver transplant

Therapie der Hepatitis C bei Patienten mit Zirrhose sowie vor und nach Lebertransplantation

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