Sirolimus has a potential to influent viral recurrence in HCV positive liver transplant candidates

Wagner, Doris; Kniepeiss, Daniela; Schaffellner, S.; Jakoby, E.; Mueller, Helmut; Fahrleitner‐Pammer, Astrid; Stiegler, Philipp; Tscheliessnigg, Karlheinz; Iberer, F.

doi:10.1016/j.intimp.2010.05.006

Cited by 40 publications

(27 citation statements)

References 20 publications

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“…79,80 A retrospective analysis of 141 HCV+ LT recipients demonstrated that a sirolimus-based regimen did not significantly delay the time to develop severe recurrence of HCV after LT. 79 In contrast, in a prospective cohort of 67 patients (39 received sirolimus, 28 received calcineurin inhibitors), the sirolimus group had significantly lower HCV-RNA levels and increased survival. 81 In addition, two independent retrospective studies (N51274 and 313) have demonstrated with sirolimus a reduction in the degree of fibrosis and the rate of progression in HCV+ LT recipients. 82,83 However, an analysis of 26,414 patients (12,589 with HCV) in the UNOS/SRTR database suggested a link between sirolimus use and risk of death and graft loss after LT in HCV patients that was not seen in patients without HCV.…”

Section: Immunosuppressive Regimensmentioning

confidence: 99%

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

Bunchorntavakul¹,

Reddy²

2014

JCTH

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Management of hepatitis C (HCV) in liver transplantation (LT) population presents unique challenges. Suboptimal graft survival in HCV+ LT recipients is attributable to universal HCV recurrence following LT. Although eradication of HCV prior to LT is ideal for the prevention of HCV recurrence it is often limited by adverse events, particularly in patients with advanced cirrhosis. Antiviral therapy in LT candidates needs careful monitoring, and prophylaxis with HCV antibodies is ineffective. Early antiviral therapy after LT has been investigated, but no clear benefit has been demonstrated. Protocol liver biopsy is generally recommended in HCV+ LT recipients, and antiviral therapy can be considered in those with severe/ progressive HCV recurrence. Sustained virological response (SVR) can be achieved in approximately 30% of LT recipients with pegylated interferon/ribavirin (PEG-IFN/RBV) with survival benefit, but adverse effects are common. Favorable patient characteristics for response to therapy include non-1 genotype, previously untreated, low baseline HCV-RNA, and donor IL28B genotype CC. Direct acting antiviral (DAA)-based triple therapy is associated with higher rates of SVR, but with similar or slightly higher rates of side effects, and immunosuppressive regimens need to be closely monitored and adjusted during the treatment period. Notably, the safety and efficacy of HCV treatment are very likely to improve with newer generation DAA. The benefit of immunosuppressive strategy on the natural history HCV recurrence has not been well elucidated. Based upon available evidence, cyclosporine A (CSA), mycophenolate mofetil (MMF), and sirolimus appear to have a neutral or small beneficial impact on HCV recurrence. Donor interleukin 28 B (IL28B) polymorphisms appear to impact the course and treatment outcomes in recurrent HCV. Retransplantation should be considered for patients with reasonable survival probability.

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Section: Immunosuppressive Regimensmentioning

confidence: 99%

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

Bunchorntavakul¹,

Reddy²

2014

JCTH

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“…24 Studies on liver transplantation reported a beneficial effect of mTOR inhibitors on viral load in HCV patients after liver transplantation in comparison to CNI-based regimens. 7,9 A retrospective cohort study enrolled 67 HCV-positive recipients of liver transplantation, 39 on mTOR inhibitors and 28 on CNI since the transplant. All patients received a maximum dosage of prednisolone until month 3 and mycophenolate mofetil.…”

Section: Discussionmentioning

confidence: 99%

“…The study also reported improved survival rates after liver transplantation of HCVpositive patients receiving SRL in comparison to patients on calcineurin inhibitor-based regimens. 7 No significant changes in the logarithm of viral copies nor any alteration of liver function was observed in HCVpositive kidney transplant recipients that switched to SRL, but liver transplant recipients on SRL monotherapy showed a decrease in viral replication. 8,9 Similar to SRL, everolimus (EVR) is a potent mTOR inhibitor (mTORi) and has been used as an immunosuppressive agent in kidney transplantation.…”

Section: Introductionmentioning

confidence: 90%

“…A follow-up time of one year is another restriction, although in a study with liver recipients, it was possible to observe different responses in a small number of patients after 9 months of treatment. 7 The use of mTORi subsequent to transplantation could lead to a more efficient prevention of viral replication; however, in the present study, patients were enrolled in the trial more than 23 months after transplantation.…”

Section: Graphmentioning

confidence: 95%

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Effect of conversion from calcineurin inhibitors to everolimus on hepatitis C viremia in adult kidney transplant recipients

et al. 2018

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Efeitos da conversão de inibidores da calcineurina para everolimo na viremia por hepatite C em receptores adultos de transplantes renais Introdução: Atualmente não há um protocolo imunossupressor específico para os receptores de transplantes renais portadores de hepatite C (HCV). Assim, o objetivo deste estudo foi avaliar o efeito da conversão a Everolimo (EVR) na HCV em receptores adultos de transplantes renais. Método: Trata-se de um estudo unicêntrico, prospectivo, randomizado, exploratório, controlado, aberto em receptores de aloenxertos renais com sorologia positiva para HCV. Os participantes foram randomizados para conversão a EVR ou manutenção dos inibidores da calcineurina. Resultados: Trinta pacientes foram randomizados e 28 foram acompanhados por um período de 12 meses (grupo de conversão, Grupo 1 = 15 e grupo controle, Grupo 2 = 13). Níveis de RT-PCR HCV descritos em valores logarítmicos foram compará-veis entre os grupos e entre pacientes em um mesmo grupo. A análise estatística não mostrou efeitos de interação entre tempo e grupo (valor p G*M = 0,852), ao longo do tempo em cada grupo (valor p M = 0,889) e entre grupos (valor p G = 0,286). O Grupo 1 apresentou uma maior incidência de eventos de dislipidemia (p = 0,03) e proteinúria (p = 0,01); não houve diferença na incidência de anemia (p = 0,17), diabetes mellitus de início pós-transplante (p = 1,00) ou infecção do trato urinário (p = 0,60). A TFGe média foi semelhante nos dois grupos. Conclusão: Nosso estudo não mostrou redução da carga viral após conversão a EVR com manutenção do tratamento antiproliferativo. ResumoPalavras-chave: Imunossupressão; Hepatite C; Transplante Renal; Carga Viral. Introduction:Currently, there is no specific immunosuppressive protocol for hepatitis C (HCV)-positive renal transplants recipients. Thus, the aim of this study was to evaluate the conversion effect to everolimus (EVR) on HCV in adult kidney recipients. Method: This is an exploratory single-center, prospective, randomized, open label controlled trial with renal allograft recipients with HCV-positive serology. Participants were randomized for conversion to EVR or maintenance of calcineurin inhibitors. Results: Thirty patients were randomized and 28 were followed-up for 12 months (conversion group, Group 1 = 15 and control group, Group 2 = 13). RT-PCR HCV levels reported in log values were comparable in both groups and among patients in the same group. The statistical analysis showed no interaction effect between time and group (p value G*M = 0.852), overtime intra-groups (p-value M =0.889) and between group (p-value G = 0.286). Group 1 showed a higher incidence of dyslipidemia (p = 0.03) and proteinuria events (p = 0.01), while no difference was observed in the incidence of anemia (p = 0.17), new onset of post-transplant diabetes mellitus (p = 1.00) or urinary tract infection (p = 0.60). The mean eGFR was similar in both groups. Conclusion: Our study did not show viral load decrease after conversion to EVR with maintenance of antiproliferative therapy. AbstRAct

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“…Pre-transplant antiviral treatment is poorly tolerated in Child C patients (Melero et al, 2009). The antifibrotic effect of sirolimus has been considered to have a potential impact on slowing down fibrosis progression in HCV-positive recipients (Wagner et al, 2010). A recent study on 88 patients treated with sirolimus-based immunosuppression reports that, although timing or severity of post-transplant HCV recurrence were not affected, hepatitis activity and fibrosis scores were lower on serial biopsy compared to conventional immunosuppression regimens (Asthana et al, 2011).…”

Section: Immunosuppression In Liver Transplantationmentioning

confidence: 99%

Current Immunosuppression in Abdominal Organ Transplantation

Girlanda¹,

Matsumoto²,

Melancon³

et al. 2012

Immunosuppression - Role in Health and Diseases

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Sirolimus has a potential to influent viral recurrence in HCV positive liver transplant candidates

Cited by 40 publications

References 20 publications

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

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

Effect of conversion from calcineurin inhibitors to everolimus on hepatitis C viremia in adult kidney transplant recipients

Current Immunosuppression in Abdominal Organ Transplantation

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