编者按：“2018年CSH-EASL DAY”于“2018年中华医学会肝病学分会学术年会”期间举行，法国巴黎Pitié-Salpêtrière医院肝脏胃肠科Dominique Thabut教授代表欧洲肝脏研究学会（EASL）在会上分享了欧洲在肝硬化并发症和肝脏移植方面的研究进展、最新观念和临床实践经验，并于会后就肝硬化患者的生存趋势、预后预测和治疗问题接受了《国际肝病》的专访。

 

近十年来，代偿期和失代偿期肝硬化患者的长期生存趋势如何？

 

代偿期和失代偿期肝硬化的预后在当前世界各国整体呈现越来越好的趋势。这是因为预防性使用抗生素和β受体阻滞剂，以及某些患者接受经颈静脉肝内门体分流术（TIPS）治疗，使肝硬化并发症获得了更好的治疗，尤其是在控制出血方面。此外，我们开始治疗HCV和HBV，阻止病毒复制。

 

然而，肝细胞癌（HCC）的发病率正在增加。NASH的发病率也在增加，但我们没有任何可以针对NASH病因的治疗方法。肝硬化患者生存改善的趋势可能会因此停止，在未来，我们可能会看到肝硬化患者的生存率再次降低。

 

: How about long-term survival trends in patients with compensated and decompensated cirrhosis during recent decade?

 

Prof. Thabut: The prognosis for compensated and decompensated cirrhosis is getting better, and this is the trend worldwide. This is because antibiotic prophylaxis and beta-blockers (and TIPS in some patients) have made the management of complications better, especially bleeding. Also, we are starting to treat HCV and HBV, and stopping virus replication. 

 

However, the incidence of HCC is growing. The incidence of NASH is growing. We don’t have any treatment for the causal factors of NASH, so we should expect that this improvement in survival will stop. In the future, we may see a decrease in survival again in cirrhotic patients.

 

除Child-Pugh和MELD评分外，是否新预测模型常用于失代偿期肝硬化的预后评估，肝移植的器官分配？

 

对肝硬化患者的预后进行评估是非常重要的。Child-Pugh评分源自临床实践，非常实用，已经使用了五十余年。但Child-Pugh评分仍存在一定的局限性，就是主观性强，特别是在评估肝性脑病和腹水时，也与紧急情况下不能使用白蛋白有关。

 

MELD评分?未必更好。事实上，与Child-Pugh评分相比，其在预测预后方面的作用是相同的，但是评估指标更为客观。然而，MELD评分也远非完美，用于移植器官分配时，未评估肝性脑病、腹水和HCC情况。

 

目前已开发出其他评分，特别是关于器官衰竭的，如CLIF-SOFA评分。据Thabut教授介绍，这些评分尚不能用于移植器官分配，所以从事肝移植手术的医生们正在尝试通过添加其他参数来完善MELD评分，例如纳入血钠水平和肝性脑病。

 

这些新评分依然有局限性，其主观性指标占比重，由于病情变化必须每天评估肝功能情况。但临床上有时并不能获得肝性脑病、腹水等变量，这是一个现实问题。“在评估肝硬化患者的生存方面，我们很难得到一个完美的评分，但是Child-Pugh和MELD评分也还不错。”

 

: Are there any other prognostic models besides Child-Pugh and MELD score commonly used to assess prognosis, including organ allocation for liver transplantation in patients with decompensated cirrhosis? What are the main limitations of these scores?

 

Prof. Thabut: This is a very important question for assessing the prognosis of cirrhosis. The Child-Pugh score have been used for fifty years, and it works very well because it was made by a clinician. Ascites is important, and encephalopathy is important. The drawbacks of Child-Pugh is that it can be subjective, especially in the assessment of encephalopathy and ascites, and also because albumin is not available in an emergency setting. 

 

MELD score is not necessarily better. In fact, it is the same as the Child-Pugh score at predicting prognosis, but it is more objective. However, the score is far from perfect, because it is used for organ allocation for transplant, but does not include encephalopathy or ascites or HCC. 

 

Other scores have been developed, especially regarding organ failure, like the CLIF-SOFA score. They are not used in the transplant setting as far as I know. They also have drawbacks. So people who work with liver transplantation are trying to improve the MELD score by adding other parameters, such as natremia and encephalopathy, but these are not used on a regular basis. The drawbacks of these scores is that subjectivity can be important, and that liver function has to be assessed every day because it varies over time. This is a real issue. Sometimes, we cannot include variables like encephalopathy or ascites that vary also. It is difficult to have a perfect score to assess survival in cirrhosis, but Child-Pugh and MELD are not so bad.

 

干细胞和人工肝支持系统在肝硬化并发症治疗中的作用如何？

 

Thabut教授在采访中指出，早在二十年前，干细胞就是一个非常有前景的研究方向。巴塞罗那小组在今年的EASL年会上提供了最新的动物研究数据，结果提示注射干细胞可改善门静脉高压症，这为进一步的研究打开了大门。

 

在同源肝脏移植方面也是如此，来自瑞士的一项研究显示，大鼠在接受小鼠的肝脏移植后可存活四个月之久。所以，这些都是新的选择。“当然，我们渴望看到所有这些研究的最终结果。”

 

Thabut教授认为，人工肝支持系统只是一种过渡，而不是肝脏疾病的最终治愈方法，它可以用于治疗某些表现，但不能从根本上解决问题。

 

: What’s the role of stem cells and artificial liver support systems in the management of complications of cirrhosis?

 

Prof. Thabut: There has been a lot of hope around stem cells, even twenty years ago. There were data presented at EASL by the Barcelona group on animal studies where injecting stem cells was improving portal hypertension. That opens the door for further research even in transplantation with syngeneic livers. There is a Swiss study showing that you can transplant rats with mouse livers with survival up to four months. So these are new options. Of course, we are eager to see the results of all these studies. 

 

Artificial support of the liver is just a transition, rather than a definitive cure of the liver disease. It can be used in certain indications, but does not solve the problem.