肝移植手术起源于1963年的美国，历经半个世纪的蓬勃发展，在全球都已进入成熟期。随着现代科学技术的不断发展、新型免疫制剂的应用和临床经验不断积累，肝移植围手术期发病率以及死亡率都已下降，术后存活率以及存活时间不断提高。我国肝移植事业虽然起步较晚，但随着医疗技术和设备的迅速发展，在移植数量和质量方面已跻身国际先进行列。我国由于乙型肝炎流行，乙型肝炎肝移植占比远高于西方国家，肝移植相关话题也始终受到临床关注。
第57届欧洲肝病研究学会年会（EASL2022）暨2022年国际肝脏大会TM（ILC 2022）上，意大利帕多瓦大学医院Patrizia Burra教授主持了肝移植热点话题论坛，并做了关于肝移植的专题报告。《国际肝病》记者有幸在现场采访了Patrizia Burra教授，请她围绕肝移植临床现状、新冠病毒肺炎疫情对肝移植的影响、肝癌肝移植适应证、降低移植术后疾病复发等话题进行阐述。
《国际肝病》
在今年的EASL大会上，您做了关于肝移植的专题报告。目前全球肝移植的临床现状如何？
Patrizia Burra教授
在过去50年里，肝移植已成为全球所有终末期肝病患者的重要治疗选择。近年来，伴随手术技术改进、免疫抑制管理和原发疾病复发预防等措施，我们在这一领域取得了很大进步。也正因此，世界各地肝移植中心在开展30余年的临床实践后，终于得以见证如此好的结果，这也是我们要为终末期肝病患者提供这种治疗选择的主要原因。肝移植可用于失代偿、肝硬化、肝细胞癌患者，以及慢加急性肝功能衰竭或急性肝功能衰竭患者。
英文原文：
: You made an important report on the progress of liver transplantation at the conference. Would you please first tell us the current global clinical status of liver transplantation?
Prof. Patrizia Burra: That is an important question. Globally, over the last 50 years, transplantation has become an important therapeutic option for all patients with end-stage liver disease. In recent years, we have improved a lot with different surgical techniques, the management of immunosuppression and prevention of recurrence of the primary disease. This is why we really are seeing such good results after at least 30 years of activity in different liver transplant centers around the world. That is why we need to offer this option to patients with end-stage liver disease. This can be for decompensation, cirrhosis, patients with hepatocellular carcinoma, and also patients with acute-on-chronic liver failure, or patients with acute liver failure.
《国际肝病》
您认为新冠病毒肺炎疫情给临床肝移植带来哪些影响和挑战？新冠病毒感染是否会增加肝移植候选者的死亡率？
Patrizia Burra教授
我们认为肝硬化、肝胆恶性肿瘤和肝移植患者更容易感染新冠病毒，因此决定对这三类患者进行随访。欧洲不同中心建议对这三类患者接种新冠病毒疫苗。起初，我们不知道患者接种新冠病毒疫苗后抗体应答率和保护率如何。2021年以来的数据显示，肝移植患者抗体应答率相当低，在某些情况下可能< 50%，但好消息是保护期可长达6个月。现已确定疫苗失败的危险因素，如高龄、肾功能障碍、使用免疫抑制剂，并尝试平衡这些危险因素以增加疫苗的保护水平。这在大多数情况下都是有效的，所以我觉得当前接种新冠病毒疫苗还是挺安全的。高龄、合并肾病和心血管疾病或肥胖的长期移植术后患者，是新冠肺炎的危险人群。
英文原文：
: In your opinion, what are the impacts and challenges brought by COVID-19 to clinical liver transplantation? Does COVID-19 infection increase mortality among liver transplant candidates?
Prof. Patrizia Burra: Actually, what we can say is that you know better than us, because SARS-CoV-2 appeared in China before Europe and the United States. But what has happened is that we decided to follow-up at least three categories of patients: the patients with cirrhosis; the patients with hepatobiliary malignancies; and the patients with liver transplantations. Those three categories were given priority because we thought they were much more exposed to the viral infection, and at risk of becoming COVID-positive. Vaccination were proposing and performing vaccinations in those three categories in different centers in Europe. At the beginning, we didn’t know how much response there would be in terms of reduction in antibodies against SARS-CoV-2, and for how long those patients would be protected. Now we have some data since 2021 showing that the response to antibodies is quite low in patients with a transplantation (maybe <50% in some cases), but the good news is that they can maintain the protection up to six months. We have identified the risk factors for failure of vaccination, such as old age, the presence of renal dysfunction, the use of immunosuppressants, and we try to balance these risk factors in order to increase the level of protection. It is working today in the majority of cases. So I think it is quite safe today. The problem with infection is if you have a patient who is long-term post-transplantation, maybe older, with renal disease, cardiovascular disease and maybe obese, that is the patient at risk for COVID-19.
《国际肝病》
肝移植作为肝癌根治性的手术选择，可以挽救很多患者的生命。那么，临床上哪些肝癌患者可以考虑做肝移植？关于肝癌肝移植适应证的问题，目前国内外也很难有一个共同的标准，请您谈谈您对于这个问题的看法？
Patrizia Burra教授
这是一个热门话题。今天，我们使用“移植肿瘤学”这个术语。在中国，HBV与肝细胞癌（HCC）非常常见且密切相关。HCC是最常见的肝脏肿瘤，但不是唯一的。对于HCC，全球各地都有丰富的临床实践并取得良好结果，并没有新进展。然而，在移植肿瘤学领域，已有关于如何为胆管癌患者进行肝移植的探讨，直径＜2 cm的肝内胆管细胞癌是未来的新挑战。在移植肿瘤学学术界中，还有对结直肠癌肝转移的患者进行肝移植的提议，不能切除时可考虑移植。这些话题非常小众，但仍是肝移植肿瘤学未来的挑战。
英文原文：
: As a radical surgical option for liver cancer, liver transplantation can save many patients' lives. So, which patients with liver cancer can be considered for liver transplantation? As for the indication of liver transplantation for liver cancer, it is difficult to have a common standard at present. Would you please share your opinion on this issue?
Prof. Patrizia Burra: I think that is a very hot topic. Today, we use the term transplant oncology. For you in China, HBV and hepatocellular carcinoma are very common and closely associated. HCC is the most common tumor in the liver, but it is not the only one. For hepatocellular carcinoma, there is a lot of activity and good results around the world, without any new advances happening. However, within transplant oncology, there is discussion about how to offer liver transplantation to patients who have cholangiocarcinoma. A small intrahepatic cholangiocarcinoma (<2 cm in diameter) is the new challenge for the future. Also among the transplant oncology community is the proposed liver transplantation for patients with liver metastases from colorectal cancer. When not resectable, there is consideration for transplantation. This is a very niche topic, but still a challenge for the future in liver transplant oncology.
《国际肝病》
为了降低移植术后的疾病复发，提高患者长期生存，目前可以有哪些积极的措施？未来，在这方面还有哪些有待进一步研究的需求或者方向？
Patrizia Burra教授
丙型肝炎的复发率高达75%，控制疾病复发真的很难。如今，随着新药出现，HCV感染者数量已大幅下降，而从前的丙肝患者因为进展成HCC，仍需要接受肝移植治疗。现在，有了新药和直接抗病毒药物，可以很容易地在移植后立即进行治疗以避免复发。对于在中国非常常见的乙型肝炎，我们有预防复发的标准方案。在欧洲，倾向于将核苷（酸）类似物（NAs）与抗HBV免疫球蛋白联用。而在中国，更倾向单独使用NA，甚至不用免疫球蛋白。现在对HBV的保护和预防程度较高，仅有不到 3%的患者会出现乙肝复发。
在欧美更常见的另两种肝移植适应证是酒精相关性肝病（ALD）和非酒精性脂肪性肝病（NAFLD）/非酒精性脂肪性肝炎（NASH）。对于ALD，需要采取综合措施来防止移植后再次饮酒而复发，这就需要选择患者，并在移植前后与患者和照护者共同进行综合护理。NAFLD/NASH是一个热门话题，因为需要预防移植后NAFLD/NASH复发，也要预防新的代谢综合征，实现后者在很大程度上取决于生活方式，即适度体力活动、不饮酒、避免移植术后肥胖或体重增加、低脂低糖饮食等。这些措施将有助于预防NAFLD再次发生或复发。
英文原文：
: In order to reduce the disease recurrence after transplantation and improve the long-term survival of patients, what positive measures can be taken at present? In the future, do you think there are any needs or directions for further research in this regard?
Prof. Patrizia Burra: When we had hepatitis C and a 75% recurrence rate in patients with hepatitis C, that was really difficult to manage the recurrence of the disease. Today, with newer drugs, the number of patients with hepatitis C has dropped enormously, and the old cohorts of patients with hepatitis C are still undergoing liver transplantation because they developed hepatocellular carcinoma. Now, with the new drugs and the direct-acting antivirals, it is very easy to treat patients immediately after transplantation to avoid recurrence. For hepatitis B, which is very common in China, we have a standard protocol for prevention of recurrence. There are two main objectives. One is using nucleoside/nucleotide analogs together with anti-hepatitis B immunoglobulins, that is more preferred in Europe. In China, you prefer to use a single nucleotide or nucleoside analog, even without immunoglobulins. But having said that, protection and prevention of HBV is much higher now. Only a minority of patients (<3%) will experience hepatitis B recurrence.
The other two indications that are more common in Europe and the US, for example, are alcohol-related liver disease and NAFLD/ NASH. For the alcohol-related disease, you need an integrated system to prevent the relapse to alcohol consumption after transplant, meaning you have to select patients and perform integrated care before and after transplantation with the patient and the care-givers. For NAFLD/NASH, that is a hot topic, because you need to prevent recurrence of NAFLD/NASH after transplant, but also prevent de novo metabolic syndrome, which depends very much on lifestyle, meaning physical activity, not drinking alcohol, and avoiding obesity and gaining weight after transplant, a low fat diet, a low sugar diet. That will prevent the development of either de novo or recurrence of NAFLD.
《国际肝病》
在肝移植领域，您认为有哪些亟待解决的问题？
Patrizia Burra教授
我会专注于提高移植器官的利用率。流行病学告诉我们，肝移植供体也可能有脂肪肝。所以，我认为最具挑战性的方面是移植器官灌注。机械灌注去除肝脏脂肪是一个重要课题。这将增加可用供体的数量，也可以用机械灌注减轻缺血再灌注损伤。这就是肝移植领域的未来。其他方面还包括使用更多活体肝移植、拆分供体组织和心脏死亡器官捐献（DCD）的可能性。利用不同外科技术可增加捐赠数量，利用机械灌注则有助于提高移植器官的质量。
英文原文：
: In the future, what problems do you think need to be solved urgently in the field of liver transplantation?
Prof. Patrizia Burra: I think I would concentrate on the increasing rate of utilization of grafts. If we have a graft, epidemiology tells us that the donor can also have fatty liver. So today, I think the most challenging aspect is perfusion of the graft. Machine perfusion to de-fat the liver is one important topic. That will increase the number of donors that can be used instead of being discarded. Then you can also use machine perfusion to alleviate ischemic reperfusion injury. That is the future. Together with the possibility of using more living donor liver transplants, splitting donor tissues, and DCD (donation after cardiac death). These different surgical tools will increase the number of donations at one site, and machine perfusion will help improve the quality of grafts to be used.
编辑（editor）：任珈墨（Jiamo Ren ）
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