面对新冠肺炎全球大流行，肝脏领域2020年压轴大戏——美国肝病研究学会年会（AASLD2020）作出了全程线上召开的调整，化挑战为机遇，既坚持了促进肝病交流的办会初衷，又进一步扩大了覆盖人群，更为难得的是还为参会者赢得了与2020年诺贝尔奖获得者面对面交流的机会。

 

《国际肝病》邀请到AASLD2020主席、美国辛辛那提儿童医院医疗中心Jorge A. Bezerra教授，就AASLD2020在疫情中的调整、美国肝病诊疗因疫情而遭受的影响和应对策略，以及他的重点研究方向——儿童胆道闭锁领域的最新研究进展进行了分享。

 

AASLD2020化挑战为机遇

 

采访中，Jorge A. Bezerra教授首先表达了希望所有听众及其家人、朋友在此疫情期间一切安好的期望。AASLD年会是一年一度的肝病学术会议，为AASLD成员、医疗服务人员及研究者提供肝病领域的前沿进展，帮助他们获悉最新临床诊疗指南、听取专家对热点问题的观点，同时也是同事、朋友间合作交流的平台。尽管新冠疫情令会议计划受到影响，但并没有改变会议举办及创建肝病交流平台的初衷信念。

 

肝病学是一个充满活力的领域，不断有新的发现和临床研究进展推动促进肝病患者的健康。因此，我们将挑战化为机遇，此次会议为临床医生及研究者提供了更长的提交研究摘要时间，并和科学计划委员会合作，导入数字平台以促进参会者交流，也降低了会议注册费，让更多人有机会参会。

 

此外，疫情期间的AASLD会议有两个特别之处。首先，增加了肝病和新冠肺炎的相关内容，邀请专家进行讲座。其次，会议最后为所有参会者准备了特殊的“礼物”，让参会者能有机会与2020年诺贝尔获得者Harvey J. Alter、Michael Houghton和Charles M. Rice教授交流。

 

新冠疫情使美国肝病人群和慢性肝病管理面临挑战

 

新冠疫情的流行确实对慢性肝病的管理提出了挑战。首先，存在肝病的易感人群，例如非酒精性脂肪性肝炎（NASH）、NASH伴失代偿肝硬化和免疫抑制的患者，可能因疫情造成病情加重。

 

尽管新冠病毒对肝脏无直接作用，但病毒可损伤血管及肝血窦内皮细胞，导致肝脏炎症、胆汁流量减少等继发性损伤。在COVID-19重症患者中，肝酶、胆红素升高等表现提示肝病严重。

 

其次，疫情对肝病管理造成了间接影响。在疫情高风险地区，肝病患者就医机会减少，患者及家属因担心被感染而不愿寻求帮忙，医生也会建议延后就诊，事实上，医院及诊所都正在采取有力的措施以保障就医环境的安全。疫情着实对社会经济等各方面造成影响，一些患者在疫情间医疗保险中断。

 

疫情对肝癌等患者影响较大，这类患者若不寻求专业的咨询和帮助，会导致疾病进展、预后恶化。疫情对急、慢性肝衰竭需要肝移植的患者也造成了影响，即使在肝源可获得的情况下，外科、肝病医师也需要根据医院病床的情况再做决定。令人欣喜的是，在确保患者安全的前提下，目前大家共同努力，肝移植手术仍在有序进行中。

 

AASLD2020上儿童胆道闭锁领的重要研究进展

 

胆道闭锁是严重影响儿童健康的疾病，在病因和新型生物标志物探寻、病程和并发症监测等方面的认识正逐步加深。

 

Jorge A. Bezerra教授所在的美国辛辛那提儿童医院的研究者利用胆道正常与胆道闭锁患者的胆道结构构建了类器官，即谱系胆道类器官，研究发现正常患者活检上皮和胆管周围腺体形态结构正常，而胆道闭锁患者的上皮发育延迟、异常且胆管周围腺体形态异常，这说明上皮发育延迟是胆道闭锁的主要原因之一。

 

来自德州儿童医院的两项研究也取得了重要进展，由美国国立卫生研究院资助的多中心联盟利用儿童肝病研究网络所完成。其中一项研究发现，胆道闭锁患者在肝门-空肠吻合术(Kasai手术)后，若胆道引流良好、血清胆汁酸水平低，则预后较好；相反，若血清胆汁酸水平高，则自体肝脏存活率低，多需要肝脏移植来获得长期生存。

 

胆道闭锁、Alagille综合征和alpha-1抗胰蛋白酶缺乏症是三种最重要的儿童肝病。另一项研究中，研究者分析了这三类疾病患者中血清生物标志物与肝脏硬度的相关性，发现胆道闭锁患者中MMP-7、IL-8和整合素这三种生物标志物与肝脏硬度相关。在Alagille综合征患者中，IL-8与肝脏硬度相关。alpha-1抗胰蛋白酶缺乏症患者中，结缔组织生长因子与肝脏硬度相关。

 

这两项研究揭示了特殊疾病中生物标志物的重要性，但是在门静脉高压和肝纤维化等疾病中，情况会有所不同。

 

<Hepatology Digest>: The Liver Meeting is the annual must-attend event bringing together attendees from around the world, what adjustments have been made to the meeting by the organizing committee due to the outbreak of novel coronavirus disease-2019?

 

Prof. Jorge A. Bezerra：First and foremost, I wish that you and those watching this interview are well and working together to promote health and safety among your friends and loved ones. You are right. The liver meeting is the annual event where members and all hepatology providers and investigators present the latest advances in the field. They learn about newest clinical protocols, listen to key opinion leaders present new discoveries, and lectures on hot topics in hepatology. It is also where they meet with colleagues, make new friends, and really establish new collaborations. The pandemic fragmented our plan for the meeting as we knew it. But it did not change our resolve to have the annual liver meeting and to maintain our commitment to the hepatology community. So, we decided that the liver meeting must go on. The reality is that hepatology remains a vibrant field. Despite the pandemic, hepatology has new discoveries and ongoing clinical trials that ultimately improve the health of patients with liver disease. Therefore, we made a series of efforts to turn the challenge into a major opportunity for the field. We gave clinicians and researchers more time to complete their work and submit abstracts by delaying the deadline for submission of abstracts. Then, we worked with the scientific program committee to redesign our program and put it in a digital platform in a way that also enabled interaction among the participants. Aware of the socio-economic impact of the pandemic, we also lowered the registration price so that more could participate in the meeting. More than ever, we felt we needed to share new knowledge more broadly - all over the world. Last but not least, we took two other steps to make the liver meeting really special. First, we developed a new sessions focused on COVID-19 and the liver and invited Dr. Anthony Fauci, a leader who has given consistent national advice on the pandemic in the United States, to talk about the new developments on COVID-19. At the end of the meeting, the AASLD gave a gift to all participants by a special hour-long interview with with the three recipients of the 2020 Nobel Prize for Physiology or Medicine: Drs. Harvey J. Alter, Michael Houghton, Charles M. Rice.

 

<Hepatology Digest>: The COVID-19 pandemic has caused significant impact on global health, what is its impact on the management of chronic liver diseases in high-prevalence areas?

 

Prof. Jorge A. Bezerra：You're absolutely right. The pandemic has imposed new challenges in the management of all patients with chronic liver disease. First, there is a real potential for COVID-19 to worsen preexisting liver disease in a vulnerable population, such as those with NASH or non-alcoholic steatohepatitis, those with decompensated cirrhosis, and those requiring immune suppression. Even when there is no direct effect of the virus in the liver, the virus may injure the endothelium of the blood vessels and the sinusoid, cause secondary lesion in the liver with inflammation, and decrease bile flow. It's also clear that patients with very high liver enzymes and bilirubin, which usually reflect severe liver disease, have severe COVID-19 disease.

 

The second is that the pandemic has also had an indirect effect in patients with liver diseases, who have decreased access to care in areas of high prevalence and high transmission rates of coronavirus. Sometimes the patients and family members are afraid to seek help because they are concerned they may get infected if they seek medical care at a hospital or physician’s office. The good news is that hospitals and clinics are taking extra steps to keep the environment safe. Health care providers, whenever possible, will recommend that the patients seek proper care, wherever they are, in the United States, in China and in other countries. The patients may also not seek care because they have lost health insurance. This really shows how the pandemic has impacted different socio-economic status of the patients. Patients with diseases like cancer need to be evaluated regularly to prevent progression of the disease. Otherwise, they may have more difficult outcomes.

 

The pandemic also impacted patients with chronic or acute liver failure that need liver transplantation. With a large number of occupied beds at major transplant centers, even when a new liver is available, the surgeons and hepatologists have to make decisions based on the availability of ICU, medical, and surgical beds. We are glad that the community continues to be creative and work together to still perform liver transplantation while keeping patients safe.

 

<Hepatology Digest>: How about the latest progresses in the research of biliary atresia communicated at this meeting?

 

Prof. Jorge A. Bezerra：Biliary atresia is indeed a disease of severe consequences to the health of affected children. We are moving closer to understanding the cause of the disease and identifying new biomarkers to monitor the course of disease, screen for complications, and hopefully use as endpoints for clinical trials. At the liver meeting, a group of investigators from my hospital, Cincinnati Children's Hospital, reported their ability to engineer a biliary organoid directly liver biopsies of babies with biliary atresia. They called it multi-lineage biliary organoid. Then they studied these organoid and found that epithelium and peribiliary glands are presented if the biopsies come from a normal patient. But if it comes from a patient with biliary atresia, the epithelium is delayed and abnormal and the peribiliary glands are not very well formed. Therefore, they provide the evidence there is a delay of the epithelium development as one of the main causes for biliary atresia.

 

I'll tell you about two other stories. A group of investigators from Texas Children's Hospital reported the results of two studies supported by the Childhood Liver Disease Research Network. This is a multi-center consortium funded by the National Institutes of Health in the United States. In the first study, they reported serum bile acids in children with good biliary drainage after the Kasai procedure which is the initial surgery for biliary atresia. If they have good biliary drainage and low serum bile acids, they have the best outcome. In contrast, if they have surgery and good biliary drainage, but high concentrations of serum bile acids, they have lower survival with the native liver and require liver transplantation for long-term survival. In the second study, they analyzed a group of patients with biliary atresia, Alagille syndrome, and alpha-1 antitrypsin deficiency, three important pediatric liver diseases. They correlated serum biomarkers with the liver stiff measurement. They found that in patients with biliary atresia, there was a correlation between the concentration of three biomarkers, MMP-7 (matrix metalloproteinase-7), IL-8 (interleukin-8) and endoglin with high liver stiffness measurement. They also found that for Alagille disease, there is correlation between IL-8 and high liver stiffness measurement. For alpha-1 antitrypsin deficiency, it was high level of connective tissue growth factor and liver stiffness. So, these studies show the importance of discoveries of biomarkers for specific diseases, and that the biology of portal hypertension and fibrosis is not the same role for all diseases.

 

（来源：《国际肝病》编辑部）