协助预测肝脏移植后存活率之模式

　　November 3, 2006 — 根据一项发表于11月号肝脏移植期刊的研究指出，当肝脏是来自特定捐赠者、特别是高风险捐赠者，一个新的模式或许可以协助预测肝脏移植后存活率，该模式可能可以预测移植后存活之时间长短。
　　
　　来自华盛顿西雅图后备军人事务Puget Sound健康照护系统的George N. Ioannou与其同事表示，增加肝脏移植器官机会的方式是放宽挑选肝脏捐赠者的条件。
　　
　　Ioannou医师表示，不幸的，目前并没有大家一致认同的捐赠条件，相对的，个别的肝脏移植系统使用不同且通常是以定义不清的条件来决定捐赠者是否适合进行肝脏移植，这样的条件包括捐赠者年龄、是否有高风险行为、肝脏切片显示之脂肪变性程度、冷冻缺血时间、活体外时间以及肝脏巨观。
　　
　　这项试验的目的在于发展且验证一个根据移植前捐赠者以及受赠者状况，以预测病患接受肝脏移植后存活率的模式；联合器官共享网络收集于1994年至2004年间在美国接受肝脏移植病患资料，总共有6,477位病患感染C型肝炎病毒（HCV），透过比例风险回归模式，研究者找出一个最能够预测存活率的捐赠者与受赠者特征，并将这些特征纳入多变项模式中。
　　
　　排除条件包括10岁以下、75岁以上捐赠者、活体捐赠者、部分肝脏捐赠者、心跳停止捐赠者、血清钠浓度高于170 mmol/l以上的捐赠者、多重器官捐赠者、过去已捐赠过器官病患、以及资料不全者。
　　
　　最能够预测肝脏移植后存活率的特征，包括是否感染HCV，该模式利用4种捐赠者特征（年龄、冷冻缺血时间、性别、以及种族／宗教），以及9种受赠者特征（年龄、身体质量指数、末期肝脏疾病严重度指标、联合器官共享网络病况指标、性别、种族／宗教、糖尿病、肝脏疾病成因、与血清白蛋白浓度）；HCV感染病患所使用的模式些微不同，同样的捐赠者特征、所有受赠者的特征，除了肝脏疾病成因与血清白蛋白浓度。
　　
　　作者表示，该模式突显了捐赠者与受赠者特征对于移植后存活的影响很大，这里所提出的模式或许可以转化为分数，以可能的捐赠者、受赠者、捐赠者／受赠者组合等变项，来评估器官移植后器官功能丧失的风险；该模式或许可以用为当已有特定捐赠者告知肝脏移植候选人以及医师，移植后的存活率有多少，对中度风险与高风险捐赠者来说是特别有意义的。
　　
　　试验限制包括无法校正每个移植中心的差异、无法确认资料的正确性、排除资料不足的病患，以及在研究进行的10年间，预测存活率的变数可能改变的误差。
　　
　　作者的结论是，最终，以这个模式决定风险指数以及预测存活率可能是一个评估特定活体捐赠者、受赠者或是捐赠者／受赠者组合风险较客观的方式；如果同时有2位捐赠者，预测存活率较低的受赠者接受预测存活率较高的捐赠者是比较适当的，反之亦然，因为这样可以使这两种受赠者的移植后存活率相当。
　　
　　美国肠胃医学会青年学者发展奖、退伍军人事务西北C型肝炎资源中心、退伍军人事务Puget Sound健康照护系统研究增益奖计划以及健康资源与服务部门协助赞助该研究。
　　
　　在随后的评论中，来自宾州费城Thomas Jefferson大学医院Ignazio R. Marino医师建议，应该进行以肝脏移植者为对象的大型前瞻性试验，来协助改善分配条件、并且定义模式中未来的捐赠者不会被误认为受赠者。
　　
　　Marino医师表示，如果肝脏移植候选人可以在器官分派时被分为不同的风险类别，不可避免的问题将会发生，我们应该试着寻找合适捐赠者以及受赠者吗？除此之外，我们应该试着评估病患是否太虚弱而不适合接受移植，并且建立统一的排除条件？目前为止，我们可能对于配对尚未准备完全，但是这措施将会是我们的最终目标。

Model May Help Predict Survival After Liver Transplant

By Laurie Barclay, MD
Medscape Medical News

November 3, 2006 — A new model may help predict survival after liver transplant, according to a report in the November issue of Liver Transplantation. The model may predict the length of posttransplant survival when a given donor is offered and may be particularly helpful for marginal or high-risk donors.

"One way to increase the availability of organs for liver transplantation is to expand the criteria that are used to determine whether an organ from a potential liver donor is acceptable for liver transplantation," write George N. Ioannou, from the the Veterans Affairs Puget Sound Health Care System in Seattle, Washington, and colleagues.

"Unfortunately, no such universally accepted criteria exist," according to Dr. Ioannou. "Instead, individual transplant programs use different, and often poorly defined, criteria to determine whether to use the liver of a potential liver donor for transplantation. Such criteria include donor age, donor high-risk behavior, the degree of steatosis on liver biopsy, cold ischemia time, down time, and the macroscopic appearance of the liver."

The objective of this study was to develop and validate a comprehensive model that predicts survival after liver transplantation, based on pretransplant donor and recipient characteristics. The United Network for Organ Sharing had complete data available for 20,301 patients who underwent liver transplantation in the United States between 1994 and 2003, including 6477 patients infected with hepatitis C virus (HCV). Using proportional-hazards regression, the investigators identified the donor and recipient characteristics that best predicted survival and incorporated these characteristics in a multivariate model.

Exclusion criteria were patients who had donors younger than 10 years or older than 75 years, living donors, split-liver donors, non–heart beating donors, donors with serum sodium concentration greater than 170 mmol/L, as well as patients with multiple organ transplants, previous liver transplants, and incomplete information.

To best predict survival after liver transplantation in patients without HCV infection, the model used 4 donor characteristics (age, cold ischemia time, sex, and race/ethnicity) and 9 recipient characteristics (age, body mass index, model for end-stage liver disease score, United Network for Organ Sharing priority status, sex, race/ethnicity, diabetes mellitus, cause of liver disease, and serum albumin). A slightly different model was used for patients with HCV infection, including the same donor characteristics, and all recipient characteristics except cause of liver disease and serum albumin.

"The models illustrate that variations in both pretransplant donor and recipient characteristics have a large effect on posttransplant survival," the authors write. "The models presented here can be used to derive scores that are proportional to the excess risk of graft loss after liver transplantation for potential donors, recipients, or donor/recipient combinations. The models may be used to inform liver transplant candidates and their doctors what posttransplant survival would be expected when a given donor is offered and may be particularly helpful for marginal or high-risk donors."

Study limitations include inability to adjust for each individual center; inability to verify the accuracy of the data; exclusions of persons with missing data; and the possibility that predictors of survival might have changed slightly during the 10-year study period.

"Ultimately, risk scores and predicted survivals determined from such models may be an objective
way to assess the risk of a given liver donor, recipient, or donor/recipient combination," the authors conclude. "If two donors are expected to be available at approximately the same time, it would be more equitable for the recipient with worse predicted post-transplant survival to receive the donor with the better predicted survival and vice versa since that would make the post-transplant survival of the two recipients more similar."

The American College of Gastroenterology Junior Faculty Development Award, Veterans Affairs Northwest Hepatitis C Resource Center, Veterans Affairs Puget Sound Health Care System Research Enhancement Award Program, and the Health Resources and Services Administration helped fund this study.

In an accompanying editorial, Ignazio R. Marino, MD, FACS, from the Thomas Jefferson University Hospital in Philadelphia, Pennsylvania, recommends a large prospective study of liver transplant candidates to help optimize allocation criteria and to define when a prospective donor should not be used for a prospective recipient.

"If candidates for [liver transplant] can be stratified into different risk categories at the time of the actual organ allocation, the inevitable question arises: Should we try to match donors and recipients?" Dr. Marino writes. "In addition, should we try to implement rules to assess when a patient is too sick for [liver transplant] and have uniform delisting criteria?.... We might not be ready to match donors and recipients yet, but this procedure should be our ultimate goal."

Liver Transplantation. 2006;12(11):1574-1576, 1594-1606