Severe liver disease is a critical clinical syndrome caused by acute and widespread hepatocyte death and severe impairment of liver function due to hepatitis virus, drugs or other causes, mainly manifesting as jaundice, hepatic encephalopathy and coagulation dysfunction, etc. It is characterized by rapid onset, rapid progression, complex disease and a mortality rate of more than 70%, making treatment quite difficult. Liver transplantation Conventional medical treatment and simple non-biological artificial liver treatment are unable to reverse the prognosis of severe liver disease. The one-year survival rate of patients with severe liver disease treated by liver transplantation is 60% to 90%, but the problem of insufficient donor livers severely limits the widespread use of liver transplantation, according to incomplete statistics, the ratio of recipient to donor in China is 150:1, that is, only one out of 150 patients waiting for a donor can receive a liver transplant. As an early liver transplantation in China, Nanjing Gulou Hospital has hundreds of liver transplantation cases so far, including improvements in new surgical methods such as living liver transplantation and split liver transplantation to solve the lack of donor livers. In addition, in order to extend the lives of more people, the Ministry of Health and the Red Cross Society of China have recently launched a pilot program for organ donation after cardiac death (DCD), also known as Non-Heart Beating Donation (NHBD), which refers to the donation of organs by citizens after cardiac death. It is a transplantation procedure that begins after a doctor declares clinical death, using medical means to maintain the function of vital organs, and after the family determines to make a donation. As one of the first DCD (Cardiac Death Donation) transplantation pilot centers in the province, our hospital also actively carries out DCD liver transplantation to further alleviate the lack of donor liver from the source. Artificial liver therapy Although the challenge of lack of donor livers has been alleviated with the DCD work, due to the very rapid progression of severe liver disease patients, there are often cases where patients lose their chance of survival while waiting for a matching donor liver in this process. Artificial liver systems can serve as a bridge by briefly replacing liver function and keeping the patient alive to buy time to find a donor liver for liver transplantation or to recover liver function on its own after treatment. Artificial liver systems can be divided into BAL (biological artificial liver) and NBAL (non-biological artificial liver) according to whether they contain cellular materials. BAL has an unparalleled advantage in replacing liver function due to the introduction of cellular materials with synthetic and metabolic functions similar to those of the liver. At present, there are several BALs entering clinical trials at home and abroad, but how to obtain sufficient cellular materials conveniently and optimize the bioreactor for culturing cellular materials are yet to be solved for entering clinical applications. Our team has spent nearly 15 years on the development of BAL, and finally constructed a new bioartificial liver support system in 2010 by using a 2:1 co-culture system of porcine liver cells and bone marrow mesenchymal stem cells as cell materials, combined with a multilayer plate bioreactor based on chitosan nanofiber scaffold developed by ourselves. The co-culture of porcine hepatocytes and bone marrow mesenchymal stem cells can better maintain and promote the function of hepatocytes, which can be considered as a more ideal and feasible BAL cell material. The overall performance is better than the existing reactors at home and abroad, and it is the first reactor with independent intellectual property rights in China. After animal experiments to verify the safety and ethical committee approval, it is now in the clinical trial stage, and the results show that patients have improved various indexes and good results after treatment, and no xenogeneic rejection or PERV virus infection has been found. Porcine hepatocytes are the first choice for many BAL systems at home and abroad because of their convenience and sufficient quantity as BAL cell material, but after all, they are cells of xenogeneic origin, and theoretically the most ideal cell material is hepatocytes differentiated from human stem cells. With the continuous development of technology, stem cells are expected to completely solve the difficulties of their large-scale proliferation culture and low differentiation efficiency to hepatocytes, and become the ideal cell material that BAL can operate, thus avoiding the possible safety doubts caused by the use of allogeneic cell material. While our new bioartificial liver support system is entering clinical trials, we are also conducting in-depth research on stem cells as an ideal cell material, and have obtained strong funding from the Chinese Academy of Sciences. Early this year, the Chinese Academy of Sciences established the Strategic Pioneer Project on Stem Cells and Regenerative Medicine to focus on key core technologies such as stem cell regulation, core mechanism of stem cell therapy, and stem cell application system. Artificial liver combined with liver transplantation For patients with severe liver disease, liver transplantation is the only effective means, but it is difficult to wait for a donor liver, and the disease progresses rapidly, so the artificial liver system can replace the liver function to temporarily maintain the patient’s life, in order to wait for the arrival of a suitable donor liver, and finally successfully perform liver transplantation, and get a second life. The artificial liver combined with liver transplantation is a new model for the treatment of severe liver disease, which can largely alleviate the problem of lack of donor livers in terms of both the source of donor livers and the waiting time for patients, and create a new situation in the treatment of severe liver disease. Since 1998, our transplantation center has been performing artificial liver combined with liver transplantation for severe liver disease, and has completed more than 100 cases so far, forming its own professional characteristics in artificial liver and liver transplantation, which is one of the case groups with better efficacy in China. Among them, 14 patients with severe liver failure have been treated with our first generation BAL 16 times, and all of them have successfully undergone biological artificial liver treatment, 2 cases have improved, and 10 cases have successfully transitioned to the liver transplantation stage and finally been able to undergo liver transplantation, which illustrates the effectiveness and prospect of the new model of BAL combined with liver transplantation for severe liver disease from clinical examples. As a result, our team has won the Chinese Medical Award, the Second Prize of Science and Technology Progress of the Ministry of Education and the First Prize of Science and Technology Progress of Jiangsu Province. Therefore, we believe that this new treatment model of artificial liver combined with liver transplantation, especially after the development of DCD work and the application of BAL system, not only greatly alleviates the problem of lack of donor liver, but also fundamentally reverses the prognosis of severe liver disease, and is a more ideal model for modern treatment of severe liver disease at present.