Artificial liver： replacing the diseased liver is better than fighting Covid-19.

　　Pay attention to the development of artificial organs ①

　　Editor’s Note Recently, the Medical Equipment Industry Development Plan (2021— 2025) passed the expert argumentation. The plan puts forward seven major areas that China’s medical equipment industry will focus on in the next five years, one of which is the field of interventional devices including artificial organs.

　　In recent years, with the rapid development of biomedical engineering technology, the research on artificial organs has also made great achievements. Its appearance and clinical application have broadened the ways of disease treatment and brought more patients back to life. To this end, this newspaper specially planned a group of reports, focusing on the achievements in the field of artificial organs and exploring its future development direction.

　　For artificial organs, many people will have a stereotype — — It should look at least like the original organ, with a nose like a nose and eyes like eyes. But in reality, artificial liver is born out of the ordinary way — — First pursue the spirit likeness, then pursue the likeness.

　　Artificial liver is actually a kind of blood purification system. In the process of completely closed extracorporeal circulation, the pathogenic factors in the blood are effectively removed and then the blood is directly returned to the human body through special fiber membrane molecular sieve and plasma separator, filter, adsorber and other equipment made of adsorption materials. According to its composition and properties, artificial liver can be divided into three types: non-biological artificial liver, biological artificial liver and mixed artificial liver.

　　Synthesis, detoxification, metabolism, these are the main functions of the real liver, and the artificial liver does not fall behind. In the tough battle against severe and critical COVID-19, artificial liver is "out of the circle" because of its super ability, and it has become a new force to block the cytokine storm.

　　"Power War" cytokine storm

　　In the battle against the COVID-19 epidemic, artificial liver brought many patients back to life.

　　This kind of "coming back to life" is completely different from the scene shown in the TV series: it is not an instant input of true qi, but the courage, persistence and grinding wait of tug-of-war with death for dozens of days.

　　"Shock, coma, dilated pupils, no response to light." Nearly a year later, as a frontline doctor, Zhang Yimin, the chief physician of the First Affiliated Hospital of Zhejiang University School of Medicine (hereinafter referred to as the First Affiliated Hospital of Zhejiang University), can still clearly describe the clinical manifestations of a critically ill patient who is also a medical staff.

　　Prior to this, the patient’s condition was repeated and aggravated. The shadows in CT images of the lungs are getting bigger every day, and the expansion speed of the lesions even makes people feel the approaching of death. The secondary septicemia and sepsis accelerated the pace of death.

　　In the process of fighting for life with death, the team led by Li Lanjuan, an academician of China Academy of Engineering and director of the State Key Laboratory of Infectious Diseases, used Lee’s artificial liver, stem cells and microecology for many times, which made the cytokines of patients return to normal level.

　　Li Lanjuan elaborated on the role of artificial liver here in great detail. She said: Li’s artificial liver first led blood out of the human body, separated blood cells from plasma, discarded a lot of inflammatory mediators and supplemented fresh plasma; Then, the patient’s plasma is absorbed by the in vitro adsorption column, which greatly reduces the inflammatory mediators and toxic substances of large and medium molecules, and at the same time, it is combined with plasma filtration to remove the toxins of small and medium molecules. Through the organic combination of plasma exchange, continuous dialysis, filtration, adsorption and a series of other technologies, artificial liver effectively eliminated inflammatory factors, blocked the cytokine storm, and played a key role in the battle to save critically ill and critically ill COVID-19 patients.

　　"The effect of Li’s artificial liver treatment system has been verified in the treatment of patients with H7N9 avian influenza." Li Lanjuan said, "In the COVID-19 epidemic, we brought Li’s artificial liver system from Hangzhou to Wuhan to treat patients and save many patients from the storm of inflammatory factors." She revealed that the survival rate of patients with severe COVID-19 in the early and middle stages who were treated with Li’s artificial liver blood purification in the ICU ward of Wuhan University People’s Hospital was 100%.

　　Continuous improvement and innovation of artificial liver technology

　　People think that artificial organs are mostly substitutes, but why can artificial liver "go out of the circle" to play its role in the field of infectious disease treatment? This also starts with the birth of artificial liver in China.

　　Although hepatitis B is no longer a "high epidemic" in China, in the last century, hepatitis B virus infection became the primary cause of liver failure in China.

　　Severe liver damage endangers people’s health and life.

　　In 1986, Li Lanjuan and his team, who worked in the First Hospital of Zhejiang University, began to study the artificial liver support system. On the basis of careful study of pathophysiology and disease characteristics of liver failure, Li Lanjuan’s team systematically applied plasma exchange, plasma perfusion, hemofiltration and hemodialysis to the treatment of patients with liver failure for the first time, and formed Lee’s artificial liver system. In 1998, related research won the second prize of National Science and Technology Progress Award.

　　In practice, the artificial liver system is constantly innovating and improving. By innovatively using a plasma component separator with a pore size of only 1/10 of that of a common plasma separator for direct selective plasma exchange, the main toxins in patients with liver failure can be eliminated, and the consumption of fresh plasma can be reduced.

　　On this basis, "Li’s artificial liver system organically combines a series of technologies, such as plasma exchange, continuous dialysis, filtration and adsorption, and breaks through the ‘ Get stuck in the neck ’ Limited by technology, it has become a leading artificial liver system in the world. " Zhang Yimin said.

　　In 2013, the first prize of national scientific and technological progress was awarded to the scientific research team led by Academician Li Lanjuan from the First Hospital of Zhejiang University, in recognition of their years of research and breakthrough in theory and technology in the diagnosis and treatment of severe liver diseases.

　　"Advanced artificial liver systems need to simulate the functions of liver synthesis, detoxification and metabolism to the greatest extent, and at the same time be modular, intelligent, miniaturized, standardized, safe, reliable and can be popularized on a large scale." Zhang Yimin said that the research team led by Academician Li Lanjuan has never stopped. With the development of information technology, the team has successfully developed an intelligent Li’s artificial liver therapeutic instrument and realized the localization of functional components and control algorithms of artificial liver equipment.

　　In recent years, in the research of biological artificial liver and hybrid artificial liver, Academician Li Lanjuan’s team has also continued to innovate, keeping up with and even leading the international development frontier, and biological artificial liver has made great progress in both cell source and bioreactor. In terms of cell source, breakthroughs have been made in pig liver cells, tumor-derived liver cell lines, immortalized liver cell lines and induced differentiation of liver stem cells. In terms of bioreactor, the team also carried out innovative explorations such as microcapsule culture and funnel-shaped fluidized bed to improve the activity of hepatocytes.

　　"Li’s bioartificial liver system has undergone initial clinical trials, which will be further improved and promoted in the future, and we will try to gradually add nano-and microfluidic technologies to the design of the reactor." Zhang Yimin said.

　　Biological artificial liver can avoid rejection

　　In October, 2017, the website of China Academy of Sciences published a scientific research progress of "Bio-artificial liver is expected to be industrialized", and the protagonist of the report was the team of Hui Lijian, a researcher at the Institute of Biochemistry and Cell Biology, Shanghai Institute of Life Sciences, Chinese Academy of Sciences.

　　They realized the in vitro culture of "liver-like cells", provided the human cells needed for biological artificial liver, and successfully developed the biological artificial liver system.

　　Supported by the strategic science and technology pilot project of "Stem Cell and Regenerative Medicine Research" of Chinese Academy of Sciences and the major science and technology project of Shanghai Science and Technology Commission, Hui Lijian’s team transdifferentiated human fibroblasts into liver-like cells (hiHep cells) by transdifferentiation method, and further realized the large-scale expansion of hiHep cells.

　　In 2016, based on the research and development of the existing bioartificial liver, the Huilijian team improved the seed cells, and used human-derived liver-like cells as the seed cells in the bioreactor to construct the bioartificial liver. Because this technology uses cells from human beings, it can avoid immune rejection and is more easily accepted by patients. Later, the researchers treated a patient with severe liver failure with a new bioartificial liver support system independently developed. Up to now, 10 patients have obviously improved after receiving the system treatment.

　　Recently, the reporter of Science and Technology Daily learned that the industrialization of this bioartificial liver is continuing to advance. In the near future, functional hepatocytes produced by new technology will be applied to the treatment of human liver diseases, which is expected to be applied in clinic.