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The special session on the role of albumin in liver cirrhosis was concluded

2022-11-28 09:00/ 发布者: Jay/ 查看: 624/ 评论: 0

      On November 27, 2022, it was sponsored by the China Liver Health, planned by the "digestive community" organization, supported by the kilifu pharmaceutical science and Technology (Shanghai) Co., Ltd.,  "diagnosis and treatment standardization of cirrhosis and its complications" held as scheduled online, and numerous expert scholars at home and abroad in the field of liver diseases gathered together to deeply explore the relevant hot topic of albumin's role in cirrhosis from multiple perspectives, Assist clinicians to establish a standardized diagnosis and treatment concept for the use of albumin in cirrhosis, make rational decisions in the diagnosis and treatment of cirrhosis and its associated complications, improve the prognosis of patients with cirrhosis, and protect more patients with liver disease.

      This meeting was chaired by Prof. Xiaoyuan Xu from Peking University First Hospital and Prof. Jidong Jia from Beijing Friendship Hospital, Capital Medical University, and Prof. Rajiv Jalan, Institute of liver and digestive health, University College London, Royal Free Hospital, United Kingdom Prof. Paolo caraceni, Center for applied biomedical research, Department of medical and surgical sciences, University of Bologna, Italy, and Prof. Jidong Jia, Beijing Friendship Hospital, Capital Medical University served as invited, expert scholars in multiple liver disease fields to share discussions on hot topics of the role of albumin in cirrhosis. The academic meeting was wonderful and well attended by clinicians.

      Meeting inception, Prof. Xiaoyuan Xu first gave his remarks. According to Prof. Xu, this event was the third issue of the series of activities "International Academic Exchange Conference on standardization of diagnosis and treatment of liver cirrhosis and its complications", and also thank the kirif company once again for providing us with a very good learning and communication platform for a wide range of doctors.

Remarks to Professor Xiaoyuan Xu


      At the "international frontiers" academic section, Prof. Rajiv Jalan from the United Kingdom has given a detailed account on the biological properties of albumin and its use in different stages of cirrhosis. The complex molecular structure of albumin confers it many physiological functions, including maintenance of plasma colloid osmotic pressure, binding and transport of a variety of substances, antioxidation, anticoagulation, and immunomodulation, among others. Albumin also has an endothelial stabilizing effect, and the rise in blood pressure after albumin infusion results not only from the volume expansion effect of albumin but also from its stabilizing effect on the vascular endothelium. Additionally, albumin is able to maintain capillary permeability, which is critical for patients with inflammatory derangements in multi organ dysfunction. Albumin is not only found inside blood vessels, but also distributed outside blood vessels. Thus albumin not only exerts its effect inside the blood vessels, but also can enter the cells to protect the cells from damage.

      The two most prominent pathogenesis driving disease progression, development of complications, and death from cirrhosis are cardiovascular dysfunction and systemic inflammation. Albumin has an ameliorative effect on both of these major factors, modifying the disease natural history of cirrhosis, which theoretically supports that albumin therapy could benefit patients with cirrhosis.

      Prof. Jalan subsequently introduced a progression trajectory model for cirrhosis. Patients with compensated cirrhosis develop their first episode of acute decompensation years later. After entering the decompensation phase, patients could be classified as having ACLF with or without ACLF (stable decompensated cirrhosis, unstable decompensated cirrhosis, pre ACLF). The risk of readmission for complications or death after discharge varies among subgroups of patients, and the efficacy of human albumin varies.


Taught by Professor Rajiv Jalan


      Prof. Paolo caraceni shared this under the question "measurement of effective albumin in patients with decompensated cirrhosis: clinical and prognostic implications". Albumin is the most dominant protein in the human blood circulation. More than 90% of healthy adults have serum albumin concentrations between 40-50 g / L. One of the most important structures of the albumin molecule is the free cysteine-34 residue (Cys34), which is the main redox site of albumin and the largest pool of thiols in plasma and has antioxidant and binding effects. In healthy people, there are three main subtypes of albumin, the main subtype of which is human thiol albumin (HMA, accounting for 70-80%), and HMA can be oxidized through the Cys34 residue to produce two oxidized forms of albumin: hna1 (reversible oxidation, 20-30%), hna2 (irreversible oxidation, 5%).

      Albumin in the body of patients with decompensated cirrhosis, not only reduced in quantity but also impaired in function. In decompensated cirrhosis, the pro oxidant and pro-inflammatory state leads to significant alterations in the structure of albumin. From a healthy population, patients with acute decompensated (AD) cirrhosis, to patients with ACLF, the proportion of HMAS decreased gradually and the proportions of hna1 + hna2 and hna2 increased gradually. Patients with cirrhosis had significantly lower amounts of native albumin and significantly higher amounts of semiaminated albumin than healthy controls. As the molecular structure of albumin is destroyed, the function of albumin also occurs obstacles. From outpatients with compensated cirrhosis, AD patients, to ACLF patients, the conjugation and detoxification efficiency of albumin gradually decreased.

      Effective albumin refers to the detectable subtype of albumin with intact function. Total albumin concentrations were not significantly different between patients with acutely decompensated cirrhosis and those with ACLF, although the effective albumin concentration was significantly lower in patients with ACLF. Multiple studies have shown that the three impaired albumin subtypes, hna2, has + cys-da, and dhsa Da, can be used as biomarkers for predicting prognosis. Compared with total albumin concentration, effective albumin concentration has a higher correlation with MELD score and better predicts outcomes, including the incidence of 30 day ACLF and 90 day mortality, in patients hospitalized with acute decompensated cirrhosis. Notably, a study showed that both total and effective albumin concentrations increased significantly after 60 g human albumin infusion in outpatients with stable cirrhosis and uncomplicated ascites, whereas 1 week after administration, total albumin concentrations decreased to baseline, whereas effective albumin concentrations remained significantly higher.


Taught by professor Paolo caraceni


      Prof Jidong Jia details the concept of further staging and decompensation of cirrhosis, as well as recommendations for the use of albumin in decompensated cirrhosis, in the academic section 'the voice of China'. Professor Jia indicated that the stage of cirrhosis was divided into 5 stages from previous 2 (compensated and decompensated) to the latest European American study (compensated cirrhosis without esophageal varices, compensated cirrhosis with esophageal varices, only upper gastrointestinal bleeding, first episode of non bleeding decompensation, and second episode of any decompensation). The more detailed the staging of cirrhosis, the more helpful it is to judge the prognosis and to develop therapeutic measures in a targeted manner. However, it needs to be noted that the main etiologies in the populations studied in Europe and the United States were hepatitis C virus and alcohol, while the main etiology in Chinese cirrhotic patients was hepatitis B virus, so whether Chinese patients are suitable for this classification needs to be verified by larger cohort studies.

      In addition, Professor Jia compared the recommendations of the 2019 Chinese guideline with the 2020 British BASL guideline, the 2021 Italian aisf guideline, and the US AASLD guideline for the use of albumin in decompensated cirrhosis. Albumin when used for ascites treatment, the recommendation of Chinese guidelines is 20-40 g / day as an intermediate dose. When albumin is used for the treatment of refractory ascites, the recommended dose in Chinese guidelines is LVP (4-5l / day) + albumin 4G / L, which is lower than other guidelines. Albumin when used in the treatment of HRS and SBP, the recommendations of Chinese guidelines are all medium doses. Professor Jia pointed out that in general, albumin is recommended in decompensated cirrhosis by each guideline, and the recommended dose in the European American guideline is higher than that in the Chinese guideline. The recommendation of the Chinese guideline is more positive than before, but still somewhat reserved.

     For the 3 long-term clinical studies on the use of albumin (answer study, di Pascoli and Macht study), Prof Jia emphasized: the inability to simply draw the same or opposite conclusion by looking at the results of the studies is important to consider different study populations, control populations, treatment regimens, clinical outcomes and so on. In combination with a recent meta-analysis published by a Chinese expert team that included 42 randomized controlled studies on the efficacy of albumin, overall, long-term infusion of larger doses of albumin is still helpful in improving patient outcomes.


Taught by Professor Jidong Jia


Discussion

      In a special discussion session, Professor Lungen Lu, the first people's Hospital affiliated with Shanghai Jiao Tong University School of medicine, asked the question whether the application of albumin in patients with portal hypertension, would increase portal pressure and the risk of esophageal variceal bleeding in patients with cirrhosis. Professor Lin Bingliang, the Third Affiliated Hospital of Sun Yat sen University, asked whether the two European professors used the overavailable albumin concentration as a predictive model and whether the effective albumin concentration truly had predictive value. Professor Weifeng Zhao, the First Affiliated Hospital of Soochow University, asked questions about the correlation between the levels of serum albumin and portal thrombosis in patients with cirrhosis in European and American countries. Prof. Wei Xie, Beijing Ditan Hospital, Capital Medical University, in response to a single price to measure the effective albumin concentration, and asked questions about the requirements to submit specimens for testing. Prof. Xing WuChun, Beijing Ditan Hospital, Capital Medical University, asked about the changes in the proportion of effective albumin in total protein as the disease progressed.


      Professor Rajiv Jalan showed that long-term use of albumin is highly effective in specific patient populations, such as patients with refractory ascites and a MELD score < 15. However, at present, it is not possible to offer long-term albumin therapy to all fit patients because of tissue management and cost. There are currently 3 simple and nonexpensive methods for determining effective albumin concentrations (ischemic modified albumin measurement, measurement of HMA and hna1 / 2 ratio, and albumin binding capacity measurement), but the use of this as a routine project test in clinical practice remains to be validated by more studies. Previous animal and clinical studies have suggested that albumin reduces portal pressure by reducing the degree of systemic inflammatory response, and data from an unpublished study in which he participated also suggest that albumin infusion could be used as a potential treatment for portal hypertension.


      Professor Paolo caraceni believes that, except in Italy, the main hindrance to the long-term use of albumin in other countries lies in tissue management and costs. The answer study was cost-effective because long-term use of albumin reduced a large number of hospitalizations due to complications. When using albumin in patients with portal hypertension, the two situations of acute phase use and long-term use of albumin need to be discussed separately. If Macroalbumin is infused at once, as with any other volume expander, it increases blood volume, eventually raising portal pressure. But if it is a long-term use of albumin, the anti-inflammatory effect of albumin may become dominant, thereby counteracting the effect of the volume expansion effect on the body and eventually allowing the portal pressure to drop. Moreover, based on his findings and his experience in clinical practice, no increased risk of variceal bleeding has been reported in patients on long-term use of albumin. Also noted that long-term use of albumin did not increase the risk of pulmonary oedema in cirrhotic patients. The infusion of albumin for 6-12 months to patients with alcoholic decompensated cirrhosis has been shown to decompensate cirrhosis in such patients by reducing the incidence of cirrhosis related complications.


      Prof. Ning Qin, Tongji Hospital, Tongji Medical College, Huazhong University of science and Technology (HUST), indicated that patients with decompensated cirrhosis ACLF account for approximately 1 / 3 of all treated patients in the infectious department of our hospital, and such patients often suffer from various complications, so that the topics discussed today,"from the basis of cirrhosis, to pathophysiology, and finally to clinical research", are very important to guide clinical practice. It is important to note that we followed the indications appropriate for Chinese patients when using albumin due to the different etiology from that of European American cirrhotic patients, and the administration dose and course of albumin need to be further defined. The recommendation for albumin administration in the Chinese expert consensus, is based both on clinical studies and incorporates clinical practice and characteristics of our population.


      According to Prof YinZhong Shen at Shanghai Clinical Center of public health (Shanghai, China), the quantity and function of albumin are altered in many diseases, so monitoring the effective albumin concentration is valuable for diagnosis, disease progression and prognosis, and infusing albumin can be helpful to change the prognosis of diseases; How much value monitoring of effective albumin concentration really has to improve disease prognosis requires further exploration; In addition, any one treatment needs to be combined with multiple treatments to really benefit patients.


      Professor Yanyan Yu, Peking University First Hospital, said the introduction of effective albumin concentration and its predictive value has greatly benefited a wide range of physicians, and more needs to be focused on in the future: what are the influencing factors for effective albumin concentration reduction, and how can we slow the effective albumin concentration reduction as much as possible? In addition, albumin infusion, especially as early as possible, is of great value in patients with decompensated cirrhosis with SBP, where it can delay disease progression and reduce readmissions and kidney injury.


      According to Prof. JingHang Xu at Peking University First Hospital, most of the data in the current study are correlation studies, and we need to pay more attention to the intervention studies, such as what effect the infusion of albumin has on a certain indicator, what benefits the long-term prognosis of patients will bring, and so on.



      Professor Jidong Jia, President of the final Congress, summarized the excellent contents of the meeting. This Sino Western dialogue has greatly harvested people, not only let us learn a lot of new viewpoints, but also provide a lot of potential research topics, hope that in the future, everyone will have a better topic, more evidence when doing scientific research!


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