Long-term absence of porcine endogenous retrovirus infection in chronically immunosuppressed patients after treatment with the porcine cell-based Academic Medical Center bioartificial liver
Long-term absence of porcine endogenous retrovirus infection in chronically immunosuppressed patients after treatment with the porcine cell-based Academic Medical Center bioartificial liver
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DOI：
10.1111/j.1399-3089.2010.00617.x
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发表时间：
2010-11-01
影响因子：
3.9
通讯作者：
Chamuleau, Robert A. F. M.
中科院分区：
文献类型：
--
作者：
Di Nicuolo, Giuseppe;D'Alessandro, Alba;Chamuleau, Robert A. F. M.
背景：在急性肝功能衰竭中，临床使用基于猪细胞的生物人工肝（BAL）支持作为肝移植的桥接治疗，使患者暴露于猪内源性逆转录病毒（PERV）传播给人类的风险。当患者接受肝移植并随后受到免疫抑制时，这种风险可能会增加。作为对之前报告的患者的进一步随访（Di Nicuolo等人，2005），在BAL治疗后免疫抑制数年的相同患者群体和当时参与临床试验的医护人员（HCW）中进行PERV感染的评估。来自接受学术医学中心-BAL（AMC-BAL）治疗的8名存活至移植的患者和参与试验的13名HCW的血浆和外周血单核细胞（PBMC），检测PERV感染。一种新的定量实时聚合酶链反应assay已used.Results：8例接受肝移植后AMC-BAL治疗仍然存活下长期药理免疫抑制。目前的临床随访范围为BAL治疗后5.6至8.7年。已经开发并验证了一种新的q-real-time PCR检测方法来检测PERV感染。PERV DNA的定量限为>= 5个拷贝/1 x 105个PBMC。线性动态范围为5 x 100至5 x 106拷贝。在这两个病人和HCWs，既没有PERV DNA在PBMC中，也没有PERV RNA在血浆和PBMC samples.Conclusion：长达8.7年后，暴露于治疗与猪肝细胞为基础的BAL，没有PERV感染已被发现在长期的免疫抑制患者和HCWs的一个新的高度敏感和特异性的q-实时PCR检测。
Background:Clinical use of porcine cell-based bioartificial liver (BAL) support in acute liver failure as bridging therapy for liver transplantation exposes the patient to the risk of transmission of porcine endogenous retroviruses (PERVs) to human. This risk may be enhanced when patients receive liver transplant and are subsequently immunosuppressed. As further follow-up of previously reported patients (Di Nicuolo et al. 2005), an assessment of PERV infection was made in the same patient population pharmacologically immunosuppressed for several years after BAL treatment and in healthcare workers (HCWs) involved in the clinical trial at that time.Methods:Plasma and peripheral blood mononuclear cells (PBMCs) from eight patients treated with the Academic Medical Center-BAL (AMC-BAL), who survived to transplant, and 13 HCWs, who were involved in the trial, were assessed to detect PERV infection. A novel quantitative real-time polymerase chain reaction assay has been used.Results:Eight patients who received a liver transplant after AMC-BAL treatment are still alive under long-term pharmacological immunosuppression. The current clinical follow-up ranges from 5.6 to 8.7 yr after BAL treatment. A new q-real-time PCR assay has been developed and validated to detect PERV infection. The limit of quantification of PERV DNA was >= 5 copies per 1 x 105 PBMCs. The linear dynamic range was from 5 x 100 to 5 x 106 copies. In both patients and HCWs, neither PERV DNA in PBMCs nor PERV RNA in plasma and PBMC samples have been found.Conclusion:Up to 8.7 yr after exposure to treatment with porcine liver cell-based BAL, no PERV infection has been found in long-term immunosuppressed patients and in HCWs by a new highly sensitive and specific q-real-time PCR assay.