编者按：今年的“第68届美国肝病研究学会年会”特别设置了 “State-of-the-Art Lecture”专题，邀请在肝癌肝移植、肠道微生态与肝脏、药物性肝损伤和慢加急性肝衰竭这四大研究领域的顶级大师分享最新学术动态，为与会医生和研究者们指点江山。
《国际肝病》前方记者邀请到来自美国明尼苏达大学医学中心John R. Lake教授，请他分享在22日“Thomas E. Starzl Transplant Surgery State-of-the-Art Lecture”专题中介绍的精彩内容。
一、器官分配方式
据Lake教授介绍，目前有两种器官分配方式：一种方式是对患者进行分组，另外一种方式是对患者进行排序。对患者进行分组的定义为根据供者医院或移植中心所处的地理区域进分配器官，整个美国划分为11个区域，有52个所谓的供者服务区（DSA）。目前，主要的器官分配区域为DSA，除非为极晚期急性肝衰竭患者（第1种情况）、极晚期肝病儿童患者（1b情况）或者终末期肝病模型（MELD）评分>35的患者。我们应用MELD评分，对器官分配中心内移植等待名单上的患者进行排序，目前，多数移植（大约60%）是在当地DSA进行。
二、器官分配的地区差异
在器官分配上，美国确实存在明显的地区差异，不同地区的移植率可相差4倍，等待肝移植期间的患者死亡风险可相差3倍。另外，如果考虑患者接受肝移植的主要指标，美国不同地区接受肝移植患者的中数MELD评分也存在极大的差异，从低至24分到超过35分，这一地区差异对某位患者是否可以接受移植具有很大的影响。或者解释为，患者的病情必须严重到什么程度，才能成功争取到供肝。在美国的某些地区，诸如加州或明尼苏达州，必须是病情特别严重的患者才能得到供肝。
三、解决器官分配地区差异问题的策略
尝试解决这一问题的第一种策略为引进MELD，用于确定肝移植等待名单上患者的优先次序，这种排序方式是从2002年开始使用的。过去15年来，我们已经对该方式进行了各种修订，但是并没有实际解决器官分配的问题。
在过去6年，我们继续努力解决这一问题。首先，我们考虑努力使供需相配，现在，像DSA等区域对器官的分配相当任意，他们并不一定反映供（可用供体器官的数量）需（移植等待名单上的人数）关系。我们首先在美国试用八区域模型，尝试对供需关系进行匹配，该模型确实相当成功，然而，最终还是失败，可能是由于变化太大所致。医生们担心对他们的中心影响太大—他们并非专注于患者，而是专注于中心。
我们已经考虑改变分配系统的其他许多方案，供者医院的周围圈可能是相当成功的策略。然而，每当做出改变时，倾向于必须使器官进行更远的旅行—更多的器官飞行，更多的移植外科医生飞行。已经对移植问题给予太多重视，希望社会可以对器官从A点改变地点到B点的新方式更加理解，并不需要雇用里尔喷射机转移器官，或者连夜转运移植外科医生去采集器官。
归根到底，我们还是没有足够的供体器官，我们所作的努力是以最精明的方式应用可用的器官。 对改变器官分配方式进行批评的另外一种观点是并没有解决可用供体器官数量不足的问题，我们应该寻找新的供体器官来源或者教育公众捐献更多的器官，正在努力进行这些工作。
肝移植后肝细胞癌（HCC）复发的风险因素和对策
影响肝移植后HCC复发的主要因素是移植时的肿瘤情况，肿瘤体积大、多个肿瘤、肿瘤侵犯血管的患者肝移植后发生HCC复发的风险较高。还可应用肿瘤标志物预测肝移植后的HCC复发风险，甲胎蛋白（AFP）常用于确定肝癌发生风险增加的人群。“我们主要通过选择合适的患者，尽量减少肝移植后的HCC复发。”目前，尚无满意的药物可以有效预防HCC复发，如果患者不幸发生HCC复发，可用的治疗选择非常有限。
Dr Lake: When you talk about organ distribution or allocation, there are two ways of looking at it. One is the grouping of the patients. The other is the ordering of the patients. The grouping of the patients is defined by the geographic area in which the donor hospital or transplant center resides. We have eleven regions across the country, and there are 52 so-called donor service areas (DSA). Currently, the primary area of distribution is the donor service area, unless patients either have very advanced acute liver failure (a status 1 patient) or a status 1b patient (which is a pediatric patient with very advanced liver disease) or a MELD score >35. We use the MELD score to prioritize patients on the wait list within that distribution unit. Most transplants (about 60%) occur within their local DSA at this time.
Dr Lake: Geographic disparity is real and is actually quite profound in the United States. The transplant rate can vary by as much as four-fold. The risk of death while on the wait list can vary by as much as three-fold. There are big differences across the country. Also, if you look at what we use as the primary indicator of geographic disparity, which is the median MELD score at the time of transplant, that can also vary quite dramatically across the country, from a low of 24 to greater than 35. This has a major impact on the likelihood of someone actually being able to undergo transplantation or not. Or equally important, how ill they have to become before they can successfully compete for a donor liver. In certain areas of the United States, like California or up in Minnesota where I live, people have to get quite ill before they can be offered a donor liver. The first strategy to try and address this problem was the introduction of MELD as a way of prioritizing people on the wait list. That occurred in 2002. We have been making all kinds of modifications over the last 15 years, but that hasn’t really addressed the unit of distribution. That is what we have been trying to address over the past six years. The first thing we looked at was trying to match up supply and demand. Right now, the regions are quite arbitrary, as are the DSAs. They don’t necessarily reflect the demand (the number of people on the wait list) and supply (the number of donor organs available). We first experimented with an eight-district model in the US, which would attempt to pair up supply and demand. And it did so quite successfully. It ultimately failed though, probably because it was a very big change. People were afraid that it would have a dramatic impact on their center – not focusing on the patients, but focusing on the center. We have looked at a number of other schemes for changing the distribution system. We have looked at circles around the donor hospitals, and that can be quite a successful strategy. But whenever you make a change, you tend to have to travel further for your organs – there is more flying of organs and more flying of transplant surgeons. I think too much emphasis has been placed on transplantation issues, because I would hope that the community would become more savvy about new ways of moving organs from point A to point B that doesn’t necessary require hiring a Learjet to transplant the organ or send transplant surgeons overnight to collect the organs. When it comes down to it, we don’t have enough organs. What we are trying to do is to use the organs we do have in the smartest way possible. One of the other criticisms of changing distribution is that it doesn’t address the number of donor organs we can access. No it doesn’t, but that is not to say that we should stop looking for new sources of donor organs or educating the public to donate more organs. Those efforts are ongoing.
Dr Lake: Primarily what affects recurrence of HCC after transplantation is the extent of tumor at the time of transplantation. Big tumors, many tumors, tumors that involve blood vessels – those are all at high risk for recurrence. We can also use tumor markers. Alpha-fetoprotein is commonly used to identify people at increased risk for liver cancer. Most of our efforts to decrease recurrence of hepatocellular carcinoma are through patient selection. We don’t have good drugs yet that are effective at preventing recurrence. If a patient does unfortunately experience recurrence, our options are somewhat limited.