A new model for treatment of severe liver disease

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Severe liver disease due to hepatitis B virus, drugs or other causes sharp and widely hepatocellular death, liver function damage caused by


Severe liver disease due to hepatitis B virus, drugs or other causes sharp and widely hepatocellular death, liver function damage caused by severe clinical syndrome, mainly for jaundice, hepatic encephalopathy and coagulation dysfunction, with acute onset, rapid progression, disease complex, the mortality rate is above 70%, the treatment is tricky.

Liver transplantation

The traditional medical treatment and simple non artificial liver treatment can not reverse the prognosis of severe liver disease. After liver transplantation in the treatment of severe liver disease patients after one year survival rate in 60%~90%, but the shortage of donor liver problems seriously restricts the wide application of liver transplantation, according to incomplete statistics, China's receptor and donor ratio reached 150:1, only 150 patients waiting for donor one can receive liver transplantation.

As in the Gulou Hospital in Nanjing city of the early liver transplantation, so far has been 100 cases of liver transplantation, the living donor liver transplantation, split liver transplantation for improvement of the new operation for liver deficiency. In addition, in order to be able to extend the lives of more people, the Ministry of health, the Chinese Red Cross recently launched a heart death organ donation that is the pilot DCD. DCD (cardiac death organ donation) refers to the citizens of organ donation after cardiac death, also known as the non heart beating organ donation (Non-Heart Beating, Donation, NHBD) in clinical doctors announced after the death of the use of medical means to maintain the function of important organs, families determined after donation, and then began to transplant. As the province's first DCD (cardiac death organ donation) transplantation pilot center, our hospital has also actively carried out DCD liver transplant surgery, from the source to further ease the problem of donor liver.

Artificial liver therapy

Although with the development of DCD work, lack of donor liver problems eased, but due to the progression of patients with severe liver disease is very fast, often lose the chance of survival in patients waiting for donor liver, the situation in the process of. The artificial liver system can replace the liver function for a short time, maintain the life of the patient, in order to gain time to find the donor liver transplantation, or after treatment of liver function can be restored, so as to play the role of the bridge. Artificial liver system according to whether the cell containing material is divided into BAL (BAL) and NBAL (non bioartificial liver), due to the introduction of the BAL with similar liver synthesis and metabolism function of cell material, so it has the advantages of NBAL compared to the alternative in liver function. At present, there are a variety of BAL at home and abroad into the clinical trial stage, but to enter the clinical application still need to solve how to easily obtain sufficient amount of cell materials and optimize the culture of cell materials, such as bioreactor.

Our team in the research and development of BAL, which lasted nearly 15 years, and ultimately to liver cells and bone marrow mesenchymal stem cells 2:1 cells co culture system for material, combined with the multilayer flat plate bioreactor chitosan nanofiber scaffold based on independent research and development, in 2010 to build a new type of biological artificial liver support system. Porcine hepatocytes and bone marrow cell material using the system of mesenchymal stem cells in co culture can better maintain and promote liver function, can be said to be a BAL cell material is ideal and feasible; multi-layer plate type chitosan nanofiber scaffold bioreactor based on the nano fiber materials and multilayer flat plate bioreactor combined, to ensure the growth of adherent cells, uniform distribution and good material exchange in the reactor volume, quantity, effective adhesion area and cell quality and other aspects of the earlier reactor has greatly improved, the overall performance is better than the existing reactor at home and abroad, and is the first in China with independent intellectual property rights of the reactor. After animal experiments verify the safety and ethics committee approval, is currently in clinical trials, the results showed that after treatment, all indexes have been improved, the effect is good, and has not yet found a xenograft rejection and PERV virus infection.

Liver cells as BAL cell material has the advantages of convenient enough, many domestic and foreign BAL system is preferred, but after all, is belongs to the heterogeneous cells, theoretically the most ideal cell material is dry cell differentiation to hepatocytes. With the continuous development of technology, is expected to solve the large-scale stem cell proliferation and differentiation into liver cells is difficult and low efficiency problem, become the ideal cell material BAL operation, so as to avoid possible security doubts brought because of the use of cellular materials dissimilar. In our hospital, the new bioartificial liver support system has entered into clinical trials, and it is also an in-depth study of stem cells as an ideal cell material. At the beginning of this year, China Academy of Sciences stem cell and regenerative medicine strategic pilot projects, over stem cell regulation mechanism of stem cell therapy, and key core technology of stem cell application system, the Affiliated Hospital of Nanjing University medical college is the special commitment of one of the units, is expected to eventually build a new safe and effective biological artificial liver system in clinical application.

Artificial liver combined with liver transplantation

For patients with severe liver disease, liver transplantation is the only effective means for liver but difficult, and progress quickly, so artificial liver system can replace liver function can temporarily maintain the lives of patients, to wait for a suitable donor liver coming, the ultimate success of given liver transplants, second lives. Artificial liver and liver transplantation for the treatment of the severe liver disease treatment mode, can wait time of two largely alleviate the lack of donor liver problems from liver donors and patients, and create a new situation in the treatment of severe liver disease.

The transplant center in our hospital since the beginning of 1998 the artificial liver and liver transplantation for the treatment of severe liver disease, has completed more than 100 cases, formed their own professional characteristics in the artificial liver and liver transplantation, is one of the effective cases. Of which 14 cases of patients with severe liver failure in our hospital using the first generation of BAL treatment in 16 cases, patients were successfully through the biological artificial liver treatment, 2 cases improved, 10 cases of successful transition to the stage of liver transplantation, eventually underwent liver transplantation surgery, from clinical case interpretation of the results and prospects of this new mode of BAL combined with liver transplantation in the treatment of severe liver disease. Our team has won the Chinese Medicine Award, the Ministry of education, science and technology progress award two and Jiangsu science and technology progress award.

Therefore, we believe that this new treatment mode for the treatment of artificial liver and liver transplantation, especially in the application of DCD and BAL to carry out the work of the system, not only greatly ease the problem of the lack of donor liver, prognosis and can fundamentally reverse the severe liver disease, severe liver disease is the ideal mode of modern treatment.



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