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肝移植临床应用中的热点和难点问题

——Ronald W.Busuttil博士访谈

[日期:2011-07-10] 来源:  作者: [字体: ]

Ronald W.Busuttil博士是朗迈尔特聘教授,大卫格芬医学院UCLA外科学分布执行主席,肝脏和胰腺移植科主任。Busuttil博士和他的团队已经进行了近5000例肝移植,因为在移植和手术方面的突出成就,他已拥有国际知名度。

美国肝移植专家

以下访谈中Ronald W.Busuttil博士就肝移植临床应用中的血型不合、补救性肝移植、劈离式肝移植以及肝移植后肾功能衰竭、肝癌复发、免疫抑制剂的应用等问题为我们进行了详细解读。

  问题一

  Hepatology Digest: According to the experiences in your center, can you talk about some innovative techniques to overcome the challenges of ABO-incompatible liver transplantation?
  《国际肝病》:我们知道,加州大学洛杉矶分校有悠久的肝移植历史。根据你们中心的经验,您能否谈谈克服ABO血型不合肝移植挑战的一些创新技术?
  Ronald W.Busuttil博士: Certainly, ABO-incompatible liver transplantation is a very challenging problem that we have to deal with. Personally, in our centre we do not perform ABO incompatible liver transplants unless it is an absolute emergency. When we do we perform plasmapheresis before the transplant to decrease the levels of circulating antibodies coupled with the administration of rituximab, an agent which decreases the antibodies further. Overall, these transplantation procedures are rare because the incidence of rejection is very high.
  Busuttil博士:当然,ABO血型不合肝移植是一个非常有挑战性的的难题,亟待解决。在我们中心,除非情况危急,否则我们不会做ABO血型不合肝移植。在移植前,我们先会让患者接受血浆置换,以减少其血液循环中的抗体,同时应用利妥昔单抗来进一步减少患者血液中的抗体。总体而言,由于它的高排斥率,这种移植方式很少被选择。

  问题二

  Hepatology Digest: Salvage liver transplantation has been performed for recurrent hepatocellular carcinoma (HCC) or deterioration of liver function after primary liver resection. For small HCC, in your opinion, should we choose to do hepatic resection, and then do salvage liver transplantation when HCC recurrence occurs, or directly do liver transplantation? Which method is better?
  《国际肝病》:补救性肝移植是用来治疗原发性肝癌切除术后肝细胞癌复发或肝功能恶化时的手段。对于小肝癌,在您看来,我们应选择先做肝切除,然后当肝癌复发时再行肝移植术,还是直接行肝移植手术?哪种方法更好呢?
  Ronald W.Busuttil博士: We believe that if you are able to perform resection in an individual who has compensated liver disease even if they have cirrhosis that this should be done, due to the fact there are just not enough organs to go around. We will perform salvage liver transplantation in some of these patients but if they are resectable we go ahead and resect them. As a matter of fact I participated yesterday in a right lobe lobectomy in a patient with compensated cirrhosis and this is exactly what we would do at UCLA.
  Busuttil博士:基于全世界都存在的器官短缺这一现状,我们认为如果术前评估处于代偿期肝脏疾病,并且能够耐受肝脏切除手术的患者,即使他们已经有肝硬化,也应该选择进行肝癌切除术。当然,我们会对某些患者实施补救性肝移植,但是如果他们是可以耐受肝脏切除的,我们就会选择再行切除术。我们昨天就完成了一台右半肝切除术,患者为代偿期肝硬化。UCLA也正是这样处理这些患者的。

  问题三

  Hepatology Digest: Can you talk about some risk factors for post liver transplant acute renal injury and failure? How to deal with it?
  《国际肝病》:您能否谈一下肝移植后急性肾功能损伤和肾功能衰竭的一些危险因素呢?这种情况发生时,我们应该如何处理呢?
  Ronald W.Busuttil博士: Renal failure is particularly a problem for those very sick patients who have a very high MELD score. Many of these patients who have been on dialysis for 30 days or more require combined kidney and liver transplantation. The biggest cause of kidney failure after liver transplantation is due to the immunosuppressive drugs that we give. These include particularly the calceneurin inhibitors which have been shown to induce nephrotoxicity and I think limiting the use of these agents in the long term is important in these patients.
  Busuttil博士:肾功能衰竭确实是肝移植术后一个棘手的问题,尤其是那些十分虚弱、终末期肝病评分(MELD评分)很高的患者。对于那些术前接受透析治疗30天以上的患者往往需要接受肝肾联合移植。我认为,免疫抑制剂的应用是肝移植术后发生肾功能衰竭的最大诱因,尤其是神经钙蛋白阻滞剂,它们已经被证实能诱导肾毒性。长期来看,我认为减少这些免疫抑制剂的应用对这部分患者非常重要。

  问题四

  Hepatology Digest:Organ shortage is a world problem. Can you talk about the application of split liver transplantation in solving this problem? What are the indications and complications of split liver transplantation? Will the patient and graft survival be worse than whole liver transplantation?

  《国际肝病》:器官短缺是一个世界性难题。你能谈谈劈离式肝移植在解决这个问题上的应用吗?劈离式肝移植的适应证和术后并发证是什么?患者和移植物的存活会不会比全肝移植差呢?
  Ronald W.Busuttil博士: There is no question that split liver transplantation is more advantageous for children than for adults. In my experience the results of split liver transplantation are equivalent to whole organs. However, in order to perform a split liver transplantation you will need a perfect graft and so extended criteria donors will not be acceptable. Therefore, I think no, split liver transplantation will not solve organ shortage but it does help in the pediatric transplant population and for those selective adult patients who can receive a split graft.
  Busuttil博士:毫无疑问,与成人相比,劈离式肝移植在儿童肝移植中的应用更具优势。根据我们中心的经验,劈离式肝移植和全肝移植的效果是相近的。然而,要进行劈离式肝移植需要一个完美的供体器官,因此很多超过标准的供体就无法使用。所以我认为,劈离式不会解决器官短缺的问题,但是它在儿童肝移植方面的确有帮助,并且对于那些能够接受劈离式肝移植的成人患者也有帮助。

  问题五

  Hepatology Digest: Can you talk about the advancement in targeted therapy in the prevention of HCC recurrence after liver transplantation?

  《国际肝病》:你能谈谈靶向治疗在预防肝移植术后肝癌复发的一些进展吗?
  Ronald W.Busuttil博士: There has not been an agent that has shown to be effective in adjuvant therapy for HCC until the advent of sorafenib which is a multi-kinase inhibitor. We are currently doing a multi-centre trial looking to see if the addition of sorafenib in adjuvant therapy will be beneficial. All previous trials have not conclusively shown a benefit because those drugs are not directly targeted for HCC whereby sorafenib is.
  Busuttil博士:HCC一直缺乏有效的辅助治疗药物,直到一种多激酶抑制剂——索拉非尼的出现。目前,我们正在进行一项多中心临床试验,研究在辅助治疗方案中添加索拉非尼是否有效。既往其他所有药物的临床试验都没有显示出明确的疗效,这是因为这些药物与索拉非尼不同,均不是直接靶向治疗HCC的药物。

  问题六

  Hepatology Digest: Can you discuss some advances in immunosuppressive regimens in liver transplantation for HCC?

  《国际肝病》:您能谈一下关于肝癌肝移植术后免疫抑制剂方案应用的一些进展吗?
  Ronald W.Busuttil博士: The only potential advancement which has yet been tested in terms of a clinical trial is the use of M-TOR inhibitors. There have been several studies looking at M-TOR inhibitors which have shown supposedly a decrease in reoccurrence. However, these have not been subjected to a randomized control trial and so the jury is still out if whether M-TOR inhibitors are going to be advantageous. Personally, I think so but we need a randomized controlled trial and we need to see the conclusions of that trial.

  Busuttil博士:经过多项临床试验研究,惟一有潜在优势的是M-TOR抑制剂的应用。目前,国际上已经有一些针对M-TOR抑制剂的研究,结果显示M-TOR抑制剂可能能降低肝癌移植术后复发率。然而,因为没有进行随机对照试验,所以仍然不能确定M-TOR抑制剂是否真的有效。我个人认为M-TOR抑制剂是有效的,但是我们需要进行随机对照试验,并且根据试验结果得出最终结论。

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