Antiviral Treatment of Patients with Recurrent Hepatitis C After Liver Transplantation with Pegylated Interferon

Schmidt, Sven; Bahra, Marcus; Bayraktar, Sandra; Berg, Thomas; Schmeding, Maximilian; Pratschke, Johann; Neuhaus, P.; Neumann, Ulf

doi:10.1007/s10620-009-0982-2

Cited by 23 publications

(14 citation statements)

References 37 publications

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“…Additionally, the post‐LT recurrence of HCV infections is one of the major causes of morbidity and allograft loss after LT 11,14–16. Because the outcomes of post‐LT therapy with the classic antiviral agents PEG‐IFN and RBV are at most moderate with respect to a sustained virological response (SVR), LT patients constitute one of the classic difficult‐to‐treat groups 16–22. Newly introduced protease inhibitor (PI)–based triple therapy now offers promising perspectives for the management of LT patients, although TVR is not yet approved for use in LT patients.…”

mentioning

confidence: 99%

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

Werner¹,

Egetemeyr²,

Lauer³

et al. 2012

Liver Transpl

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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.

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confidence: 99%

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

Werner¹,

Egetemeyr²,

Lauer³

et al. 2012

Liver Transpl

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“…A sustained virological response (SVR; ie, the patient is serum‐negative for HCV by polymerase chain reaction 6 months after the cessation of therapy) occurs in approximately 40% to 50% of patients with genotype 1 and in 80% of patients with genotype 2 or 3 9‐12. After LT, such therapy is associated with frequent adverse events, and response rates, varying between 30% and 40%, are substantially lower in all HCV‐positive patients 13‐15…”

mentioning

confidence: 99%

Relationship between the interleukin-28b gene polymorphism and the histological severity of hepatitis C virus-induced graft inflammation and the response to antiviral therapy after liver transplantation

et al. 2011

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“…Non-1 genotype [26, 27, 199, 202, 213, 218, 220, 234, 235], absence of prior antiviral therapy [194], early virologic response (evaluated after 3 months) [27, 28, 202, 205, 207–210, 214, 215, 217–221, 223, 235], rapid virologic response (evaluated after 1 month) [206, 208, 220], adherence to therapy [27, 202, 207, 211, 213, 216–218], low baseline viral load [27, 208, 211–213, 216, 221, 222], low pretreatment fibrosis stage [26, 28, 204], younger donor age [26, 28, 221, 234], polymorphisms close to the IL-28B gene [66–69], and cyclosporine-based immunosuppression [26, 234, 236] are associated with an improved SVR. Most studies demonstrated improved biochemical and histologic findings, even in virologic nonresponders [222, 237], but whether antiviral therapy slows disease progression in nonresponders has not yet been demonstrated.…”

Section: Antiviral Treatmentmentioning

confidence: 99%

Liver Transplantation and Hepatitis C

Akamatsu

Sugawara

2012

International Journal of Hepatology

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Hepatitis-C-virus- (HCV-) related end-stage cirrhosis is the primary indication for liver transplantation in many countries. Unfortunately, however, HCV is not eliminated by transplantation and graft reinfection is universal, resulting in fibrosis, cirrhosis, and finally graft decompensation. The use of poor quality organs, particularly from older donors, has a highly negative impact on the severity of recurrence and patient/graft survival. Although immunosuppressive regimens have a considerable impact on the outcome, the optimal regimen after liver transplantation for HCV-infected patients remains unclear. Disease progression monitoring with protocol biopsy and new noninvasive methods is essential for predicting patient/graft outcome and starting antiviral treatment with the appropriate timing. Antiviral treatment with pegylated interferon and ribavirin is currently considered the most promising regimen with a sustained viral response rate of around 30% to 35%, although the survival benefit of this regimen remains to be investigated. Living-donor liver transplantation is now widely accepted as an established treatment for HCV cirrhosis and the results are equivalent to those of deceased donor liver transplantation.

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Antiviral Treatment of Patients with Recurrent Hepatitis C After Liver Transplantation with Pegylated Interferon

Abstract: The outcome of antiviral combination therapy for HCV reinfection after OLT can be best predicted by week-24 virologic response. The high SVR rates in patients with detectable HCV RNA at week 12 might suggest a prolonged treatment protocol in liver transplant recipients.

Cited by 23 publications

References 37 publications

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

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

Relationship between the interleukin-28b gene polymorphism and the histological severity of hepatitis C virus-induced graft inflammation and the response to antiviral therapy after liver transplantation

Liver Transplantation and Hepatitis C

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