Liver transplantation has become the most effective choice for treating end-stage liver disease and acute explosive liver failure. According to UNOS in the United States, in the past 10 years, 26,040 liver transplants have been implemented worldwide. The 1-year and 3-year survival rates of patients in advanced transplant centers have reached 90% and 80%, respectively, and the 5-year survival rates can reach 65% to 75%. The survival rates of children's liver transplantation and relatives' living liver transplantation are higher. In addition to the extended survival time, the quality of life has been significantly improved, including restoring work and fertility. In recent years, liver transplantation in China has also developed rapidly, with about thousands of cases of annual transplantation. The number of units carried out has continued to increase, and the survival rate has been improved. The projects and levels carried out in advanced units have gradually approached the international level.

Despite these progress, liver transplantation still faces some problems that need to be solved urgently. Due to the significant increase in the success rate of surgery, the continuous expansion of surgical indications, and the problem of donor liver shortage becomes more serious. In addition, the recurrence of transplanted liver disease, especially the recurrence of viral hepatitis and liver malignant tumors, and chronic failure of liver transplantation have also become the main reasons for the failure of liver transplantation and re-liver transplantation.

1. Expand the source of liver donor

Liver donor shortage is a major problem facing countries around the world. Faced with the urgent desire of patients with terminal liver dying, exploring new sources has become our responsibility.

1. Living liver transplantation. It was originally an Asian country and region because it was almost impossible to obtain liver donors with brain death. It can be said that living liver transplantation was carried out under the circumstances of being forced. LDLT was initially controversial, but after several years of exploration and efforts, it has proved that LDLT is an effective way to solve liver shortage. In recent years, it has developed rapidly in Asia. Five centers in Japan, South Korea, Taiwan and Hong Kong reported that a total of 1,508 living liver transplants were carried out in the past 12 years, almost half of which were completed by the Tanaka group in Kyoto, and half of which were each of the children and adults. 53 cases of transplantation were 78.7% to 97.8% and 76.1% to 97.8% respectively.1. As the above-mentioned centers achieved stable results, although they were not the first to carry out live liver transplants, they cannot deny the contributions they have promoted the large-scale development of LDLT in recent years. In the United States, Europe, Canada, Australia and mainland my country, at least 80 transplant centers have successively implemented T-numbers, with 2,146 cases being implemented according to statistics from 47 units. The surgical procedures have been continuously improved, including living left hepatic transplantation, living right hepatic transplantation, 2 left liver lobes for one recipient, in situ assisted liver transplantation and domino whole liver transplantation and combined with split liver transplantation; the indications have been continuously expanded and the effect has been steadily improved. There are 92 cases in the Kaohsiung Group in Taiwan in 5 years, and the survival rate of patients and transplanted livers is 97.8%1.

The main problem of LDLT is the safety of donors. Five Asian centers have counted 15.8% of postoperative complications of donor hepatitis, 1% require reoperation, the right liver lobe is 28%, the left liver lobe is 7.5%, and the left outer lobe is 9.3%. In particular, the right liver lobe has many complications after surgery, such as cholestasis, biliary leakage, biliary stenosis, portal vein embolism, abdominal bleeding and pulmonary embolism. 2. At least 2 living donors died in the United States, and the incidence of postoperative complications is 20% to 30%. 3. Asian centers have died in the backyard without surgery, and 1 case died three years later. Long-term follow-up is needed in the future. In addition, LDLT also involves ethics and sociology issues2.

2. Borderline liver donor. Due to the severe shortage of liver donors, the possibility of applying marginal donors has been proposed in recent years. Borderline donors, namely: the time of ischemia is relaxed, the use of donors without heartbeat; the age limit for donors is relaxed, and donors older than 50 years old, and even more than 18 cases are reported by donors aged 70 years old. 4; the quality limit for donors is relaxed, abnormal liver, such as mild or moderate fatty liver, ischemic damage to the liver; the liver of donors with diabetes, autoimmune diseases, and the liver of autoimmune diseases may "heal itself in another place" after "changing ownership"; hepatitis B or C hepatitis positive

, If the recipient has hepatitis himself, hepatitis can be accepted as donors with the same hepatitis; if the liver of the diseased liver transplantation metabolic disease is reused, there is no early side effect, at least it can provide liver donors to emergency liver transplantation or liver cancer recipients, combined with split liver transplantation, one liver and two liver, or even one liver and three liver 5; if the donors of ABO blood type does not match, plasma replacement is required, etc. MinoruTanabe reported that live liver transplantation transABO blood type, in addition to preoperative plasma replacement and splenectomy splenectomy, splenectomy, splenectomy, MP, prostaglandin E1 and methanesulfonate 6.

The main problem facing marginal donor liver is delayed or incomplete recovery of transplant liver function, and the incidence of acute rejection is high. Therefore, corresponding measures must be taken during the perioperative period. Of course, the use of marginal donor liver is only a temporary measure in case of severe liver deficiency or emergency situations.

2. Viral hepatitis and liver transplantation

The epidemic of hepatitis increases the number of patients who require liver transplantation by 5 times, which makes the problem of severe shortage of donor livers more serious. In addition, when selecting donor liver donor liver donor livers, especially when living relatives donate livers, they often encounter the problem of donor hepatitis infection. Therefore, viral hepatitis is an inevitable problem that needs to be studied.

The effective treatment after liver transplantation is to control the development of hepatitis, prevent the recurrence of transplanted hepatitis and avoid retransplantation. The recurrence of transplanted hepatitis is mainly hepatitis C abroad, and the use of interferon and triazole nucleosides may prevent the recurrence of hepatitis C.

In China, hepatitis B infection is mainly caused by hepatitis B. In the case of liver donor deficiency and prevention of recurrence of hepatitis, HBV core antibody positive can be used for liver transplantation. First, consider to patients with HBV liver disease, then provide HBV antibody positive recipients, and finally consider negative recipients. The recipient is positive for anti-HBs or anti-HB core antibodies, or all positive, which cannot absolutely prevent hepatitis recurrence. Therefore, lamivudine should be tried to prevent, reduce the dosage of immunosuppressants or reduce the amount of hormones as soon as possible, or even remove hormones. 8. Studies have shown that donor HbsAg negative and anti-HB core antibody positive are not contraindications for living liver donors. 9.

Hepatitis B is the main cause of liver failure in Asia. Although the use of HBIg and Rafmiding can effectively prevent hepatitis from recurring in transplanted livers, the high cost of long-term use is limited. The method of active immunization is currently controversial. Newer nucleoside similar products are most promising. If combined with 2 or more antiviral preparations, it may be an ideal future measure to prevent hepatitis B recurrence after liver transplant10.

3. Liver, bile malignant tumors and liver transplantation

In the early stage of liver transplantation, liver cancer patients are often selected as recipients. Due to the recurrence of liver cancer, the long-term survival rate is low, and the previous reported cure rate is only 30%. Recently, new understanding of liver cancer liver transplantation has been found, and the key is to choose suitable patients. The tumor is less than 5cm or 3 tumors less than 3cm, and the effect of liver transplantation is better. According to this standard, the survival rate is similar to other chronic liver transplantation. When liver cancer is combined with cirrhosis, liver transplantation is better than partial liver resection. The 3-year survival rate of liver cell liver cancer is 83%, and partial liver resection is only 18%. The reasons may be: 1

Liver transplantation is used in about 90% of patients with liver function impaired liver function with liver cirrhosis; 2 Tumors and combined liver diseases can be treated at the same time; 3 Hepatitis and liver cancer are often multicentered, and partial hepatic resection has a high recurrence rate. Recently, S has also changed the policy of not allocating donor liver cancer recipients. Mazzaferro reported that if the waiting time before surgery exceeds 3 months, it is recommended to use chemotherapy drugs to embolize first to prevent further development of the tumor and reduce the possibility of metastasis. 12. Many centers also use radiofrequency erosion. In the future, we can further study how to deal with it more reasonably before transplantation.

The survival rate of cholangiocarcinoma is less than 20% for 2 years. The effect of liver transplantation is also disappointing, but 10% survive for more than 5 years, so it is suggested that choosing a suitable recipient may achieve better results. DeVreede reported that patients whose tumors are above the gallbladder and cannot be surgically removed will be ruled out intrahepatic metastasis, extrahepatic metastasis, and uncontrollable infections. 20 cases of cholangiocarcinoma received liver transplantation after 2 to 3 weeks of intraluminal radiotherapy. After liver transplantation, combined treatment of radiotherapy and chemotherapy was used. 91% survived for 47 months, and only one patient relapsed. Further experience is still needed.

4. The effect of HLA matching on liver transplantation

In the past, liver transplantation was generally believed to be unrelated to the degree of HLA matching, so liver transplantation does not require matching. Opelz believes that the reason why the statistical results cannot be seen in bulk case analysis may be: 1. Strong immunosuppressive treatment covers the possible differences caused by HLA matching; 2. The particularity of transplantation of liver itself can induce immune tolerance. Mann analysis 924 cases, with the same 1-year and 5-year survival rates of FK506 and CsA of 88% and 78.7%, respectively. CsA has a large number of rejection reactions. Although the survival rate is not related to HLA, the incidence of acute rejection reactions with good HLA matching is low Immunological factors: 1. Immune acute and chronic rejection reactions include cellular immune responses and humoral immune responses; 2. Unreasonable immunosuppressive medication regimens; 3. HLA degree of consistency; 4. T cell costimulation signaling system.

Nonimmunological factors include: 1. Borderline donor organs; 2. Brain trauma/brain death donors; 3. Ischemia/reperfusion and physical surgical injury; 4. Cell aging; 5. Viruses including hepatitis and CMV infection; 6. Immunosuppressant drug damage; 7. Original disease recurrence; 8. New tumors. Some complications are also related to the use of long-term immunosuppressants, such as diabetes, high cholesterol, progressive renal hypofunction, hypertension and osteoporosis. Moreover, the risk of infection and neonatal malignant tumors has also become the main causes of long-term death. Therefore, individualized treatment plans should be implemented after liver transplantation, in addition to immunosuppressant regimens and prevention and treatment measures for the above nonimmunological factors.

Six, research directions being explored

1. Hepatocyte transplantation also hopes to achieve the above goals. Bilir reported that intrasplenary and intrahepatic injection of human liver cells for 5 cases of acute explosive liver failure, 3 cases survived for 18 hours, hepatic encephalopathy, arterial ammonia and prothrombin time were improved. However, long-term survival was not obtained. The autopsy showed implanted liver cell growth, which proved the feasibility of this method.

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3. The treatment and treatment of acute explosive liver failure is very difficult. The purpose of treatment is to prevent irreversible nerve damage; 2. Provide sufficient time to fully restore liver regeneration; 3. There is time and opportunity to transition to liver transplantation. Research on artificial liver perfusion systems, biological-artificial liver system and pig liver in vitro perfusion systems is expected to achieve the purpose of preventing cerebral edema, correcting clotting mechanism disorders, and maintaining patients waiting for appropriate liver donation or self-recovery.

4. Xenotransplantation: Xenotransplantation is an alternative exploration path to solve the origin of liver. In 1993, Starzl first reported two cases of xenotransplantation of baboon liver. The recipients survived for 70 days and 26 days respectively. Although the results of the preliminary attempts are not ideal, humans have taken valuable first steps after all. 19. Currently, it is mainly used to treat explosive liver failure and liver transplantation with normal or transgenic pig liver for in vitro transfer. 20. There are still xenorejection reactions, physiological differences, pathogenic infections, ethical and psychological disorders. Professionals are still confident about the future of xenotransplantation.

5. Use autologous somatic cells to clone stem cells and build a liver that can be used for transplantation, which is equivalent to autologous transplantation in nature and fundamentally eliminates the problem of rejection. However, there are still many problems in how to cultivate a liver with complete structure and function in vitro in a directional manner. 21-22.

There are two routes of medical system in the world. One is the free medical treatment chosen by most countries, which seems very suitable for the people, but in fact there are great disadvantages. Because there are too many diseases that cannot be solved by free medical treatment, and the country cannot afford it, so it can only be dragged on. In developed countries, because of high per capita income and high quality of life, these disadvantages are hidden. But once they are placed in third world countries, this disadvantage will be infinitely amplified and can only be maintained by lowering medical standards. In the face of the new crown and in the face of a huge number of patients, even developed countries cannot withstand this wave of economic blow. The other is the market-oriented medical treatment used by domestic and American countries. The United States is almost completely market-oriented and relies on the developed insurance industry to support medical payments. What income is used for medical insurance, and what income is used for, there is a point.

Level. The domestic needs to be more humane. I have to go through a middle road for so many years, but it is really difficult. What the United States is really better than the country is its attention and respect for clinicians. There, clinicians are real doctors, with high incomes, no pressure on scientific research, and wholeheartedly serving their patients. But this is just a pure doctor. If you want to become a professor respected by everyone, you have to give up high-income positions such as private clinics and work in teaching hospitals. The salary is not much. In China, these two directions have been mixed up. There is a low income, no scientific research will not allow promotions, and you also have to take good care of clinical patients. As the pillar of the family, you are so busy that you can't take care of your family and don't have much money in the end. What should you do? Naturally, you have to find a way to make money, how to make money? There is so much news, I won't go into details here.
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