I. Overview
Liver cirrhosis is a common and frequent disease in China, with an incidence rate of 17.1/100,000. More than half of cirrhosis is caused by hepatitis B, and a few are caused by hepatitis C. There are 130 million hepatitis carriers in China, and the development of hepatitis can lead to cirrhosis.
Early cirrhosis often does not have many clinical symptoms, while late stage decompensated cirrhosis will show a series of clinical manifestations such as liver dysfunction, portal hypertension, hypersplenism, etc., such as: upper gastrointestinal bleeding, hepatic encephalopathy, liver failure and other complications, which are often fatal and pose a great threat to patients’ lives and properties, seriously affecting patients’ work and life, and greatly increasing the the medical burden of society.
Second, the treatment of cirrhosis of the liver
At present, the treatment of cirrhosis includes conservative treatment, surgical treatment and interventional minimally invasive treatment.
1.Conservative treatment.
It mainly includes hepatoprotection, reduction of portal pressure, antiviral treatment, complication treatment and other drug treatments. These treatments can only be symptomatic treatment, which is effective for early cirrhosis and can also slow down the process of cirrhosis, but treating the symptoms but not the root cause is not effective for liver disease that has developed to the end stage.
2.Surgical treatment.
Including shunt, dissection and liver transplantation. These treatments can solve portal hypertension well, especially for gastrointestinal bleeding and hypersplenism, etc. They have better efficacy. However, there are still many problems, such as: high trauma, high cost, and many complications (hepatic coma, further deterioration of liver function, and gastrointestinal disorders). Bypass and dissection do not fundamentally solve cirrhosis, but only provide some treatment for its complications. Liver transplantation is the only effective means to treat end-stage liver disease, but there are problems such as shortage of donors, high price and immune rejection.
3. Minimally invasive interventional therapy.
Interventional treatment overcomes many disadvantages of surgery, but there are certain problems with a certain method alone. For example: gastroscopic injection of sclerosing agent can quickly stop bleeding, but 40% of patients 1 year and varices; 1 year bleeding recurrence rate of 60%-70%; and can not solve the problem of portal hypertension, while often complicated by esophageal ulceration, stenosis or perforation (incidence of 14% – mortality rate of 50%), the gastric fundic varices are also ineffective.
Gastroscopic ligation.
It is 95% effective when there is no active bleeding, but the recurrence rate of bleeding is also very high, with a recurrence rate of 60%-70% in the first year; again this method does not solve the problem of portal pressure, but in comparison, there are not as many complications as sclerotherapy injection, and it is also ineffective for fundic varices. The combination of the two has no advantage and increases the side effects.
Gastric coronary vein embolization.
It provides a better short-term resolution of upper gastrointestinal bleeding; the recurrence rate of bleeding is 55% in the first year and 81% in the second year; this method does not resolve hypersplenism; its effect of reducing portal pressure is also not significant.
Partial splenic embolization.
It can better resolve hypersplenism, partially reduce portal pressure, and partially improve liver function; however, complications such as splenic abscess, bacteremia, and ectopic embolism may occur if the degree of embolization is not well controlled, and it alone is not the preferred method for resolving esophageal varices.
Transjugular portal body vein shunt (TIPPS).
The efficacy of this approach for portal vein reduction is very positive, reducing the chance of bleeding to 39%, but there are problems with hepatic encephalopathy and stent restenosis (50% restenosis rate).
Alison et al. confirmed that human bone marrow MSCs can differentiate into hepatocytes both in vivo and ex vivo, which suggests that we can isolate autologous bone marrow MSCs in vitro and transplant bone marrow hepatocytes into the patient’s liver through an interventional catheter to induce differentiation into normal hepatocytes to function and solve the problem of liver failure. And autologous stem cell transplantation, which improves liver function with definite efficacy, convenient source and no immune reaction, has no effect on portal hypertension and gastrointestinal bleeding. Therefore, all minimally invasive treatment methods alone have certain defects.
Three-dimensional treatment of liver cirrhosis.
Accordingly, we skillfully combine several minimally invasive treatment techniques so that their complications can be avoided and their advantages can be fully utilized to achieve a good therapeutic effect. We perform gastric coronary vein embolization through percutaneous puncture of the liver via portal vein, which can solve the upper gastrointestinal bleeding due to esophagogastric fundic varices, plus partial splenic embolization via splenic artery to solve the patient’s portal hypertension and hypersplenism. Because the splenic vein normally accounts for about 28% of portal blood flow, and in patients with portal hypertension it can account for 70-80%, partial splenic embolization through the splenic artery can reduce portal blood flow and lower portal pressure, and at the same time address the decrease in white blood cells and platelets caused by hypersplenism. Transplantation of the patient’s autologous bone marrow mesenchymal stem cells into the patient’s liver through an interventional catheter allows them to induce differentiation into normal liver cells to function and resolve liver failure. The clinical efficacy of the three alone is certain and has been clinically proven. Combining the three will fundamentally solve the treatment of cirrhosis and its efficacy will be better.
This technology has obvious advantages in clinical efficacy, bleeding recurrence rate, and complications compared with surgery (dissection and shunt), providing a new treatment method for the clinical treatment of cirrhosis. Moreover, we are studying whether we can combine the four techniques of TIPS, gastric coronary vein embolization, partial splenic embolization and stem cell transplantation for the treatment of cirrhosis, so that the portal vein pressure can be reduced more effectively and the liver function can be improved better. Theoretically it is sure that the efficacy will be better.
(TIPPS).
The efficacy of this method to reduce portal vein is very positive, can reduce the chance of bleeding to 39%, but there are problems such as hepatic encephalopathy, stent restenosis (50% restenosis rate), etc. TIPPS + gastric coronary vein embolization: better resolution of upper gastrointestinal bleeding, bleeding recurrence rate can be reduced to 16%/2 years; however, it cannot resolve hypersplenism and cannot improve liver function.
Alison et al. confirmed that human bone marrow MSCs can differentiate into hepatocytes both in vivo and ex vivo, which suggests that we can isolate autologous bone marrow MSCs in vitro and transplant bone marrow hepatocytes into the patient’s liver through an interventional catheter to induce differentiation into normal hepatocytes to function and resolve liver failure. And autologous stem cell transplantation, which improves liver function with definite efficacy, convenient source and no immune reaction, has no effect on portal hypertension and gastrointestinal bleeding. Therefore, all minimally invasive treatment methods alone have certain defects.
Three-dimensional treatment of liver cirrhosis.
Accordingly, we skillfully combine several minimally invasive treatment techniques so that their complications can be avoided and their advantages can be fully utilized to achieve a good therapeutic effect. We perform gastric coronary vein embolization through percutaneous puncture of the liver via portal vein, which can solve the upper gastrointestinal bleeding due to esophagogastric fundic varices, plus partial splenic embolization via splenic artery to solve the patient’s portal hypertension and hypersplenism.
Because the splenic vein normally accounts for about 28% of portal blood flow, and in patients with portal hypertension it can account for 70-80%, partial splenic embolization through the splenic artery can reduce portal blood flow and lower portal pressure, and at the same time address the decrease in white blood cells and platelets caused by hypersplenism. Transplantation of the patient’s autologous bone marrow mesenchymal stem cells into the patient’s liver through an interventional catheter allows them to induce differentiation into normal liver cells to function and resolve liver failure. The clinical efficacy of the three alone is certain and has been clinically proven. Combining the three will fundamentally solve the treatment of cirrhosis and its efficacy will be better.
This technology has obvious advantages in clinical efficacy, bleeding recurrence rate, and complications compared with surgery (dissection and shunt), providing a new treatment method for the clinical treatment of cirrhosis. Moreover, we are studying whether we can combine the four techniques of TIPS, gastric coronary vein embolization, partial splenic embolization and stem cell transplantation for the treatment of cirrhosis, so that the portal vein pressure can be reduced more effectively and the liver function can be improved better. Theoretically it would definitely have better efficacy.