Long-term Outcomes Of Autologous Bone Marrow Mononuclear Cell Transplantation In Decompensated Hepatitis B Cirrhosis And Alcoholic Cirrhosis

Background and ObjectiveDecompensated cirrhosis is a serious clinical situation due to its complications and high mortality rate. Impaired liver regeneration is associated with a poor outcome in patients with alcohol-induced liver cirrhosis and HBV-related liver cirrhosis。Orthotropic liver transplantation is by far the best treatment option for patients with decompensated cirrhosis; however, limitations such as shortage of organ donor, surgical complication, post transplantation rejection, high cost of the procedure have made it not easily available. Moreover, the prognosis of the patients with different cause cirrhosis is not the same. Autologous bone marrow mononuclear cells(BM-MNCs) transplantation has been reported to be safe and effective by several reports with short-term follow-up. We aimed to study the long-term efficacy of autologous BM-MNCs transplantation on improving liver function and reducing the complications in decompensated cirrhosis patients, and compare the therapeutic effect of BM-MNCs transplantation in patients with different types of liver cirrhosis, and to evaluate the maintenance time of the effect of transplantation, in order to seek a new ways for individual treatment for patients with cirrhosis. Methods1. A total of 43 inpatients with decompensated liver cirrhosis were recruited in this trial at Henan Provincial People’s Hospital from March 2009 to March 2011, including 30 patients undergoing a single transplantation with BM-MNCs plus routine medical treatment, and 13 patients receiving medical treatment only as control. 80-100 ml of bone marrow was obtained from each patient and the BM-MNCs suspension was transfused back into the liver through hepatic artery. The clinical symptoms condition, blood biochemistry test and complication was recorded and analyzed to monitor the efficacy by during the follow-up of 24 months.2. A total of 27 inpatients with decompensated liver cirrhosis were enrolled in this trial at Henan Provincial People’s Hospital from February 2012 to February 2013, including 15 patients with alcohol liver cirrhosis and 12 patients hepatitis B cirrhosis, all the patients undergoing a single BM-MNCs transplantation plus routine medical treatment, Bone marrow of 80-100 mL was obtained from each patient and the BM-MNCs suspension was transfused into the liver via the hepatic artery. The efficacy of BM-MNCs transplantation between two groups was monitored during the 24-month follow-up period. The efficacy and safety of BM-MNCs transplantation in different types of liver cirrhosis was evaluated. Results1 、 Bone marrow collection process and hepatic artery catheter executed successfully in all patients without special discomfort, all patients had no liver cancer developing in hepatic artery angiography. No patients with abnormal reaction in cell input process.2 、 After transplantation, the clinical symptoms and signs had improved significantly, such as Loss of appetite, weakness, jaundice, and ascites were improved.3 、 Compared with the control group, the improvement in Liver function parameters was noticed 1 month after the BM-MNCs transfusion in cirrhosis patients, firstly in prealbumin, and followed by albumin, total bilirubin, prothrombin time, prothrombin activity, fibrinogen and platelet counts. The efficacy of BM-MNCs transplantation lasted 3-12 months as compared with the control group. Differences were statistically significant. Serious disease complications such as hepatic encephalopathy and spontaneous bacterial peritonitis were also observed to be significantly reduced in BM-MNCs transfusion patients compared with over the controls. But these improvements disappeared by 24 months after transplantation.4、The improvement in liver function and coagulation function parameters was noticed 1 month after the BM-MNCs transplantation in alcohol liver cirrhosis group and hepatitis B cirrhosis group. After 6 months, 12 months, 18 months, 24 months alcoholic cirrhosis group with ALB, PA, PTA, FIB was increased higher than in hepatitis B cirrhosis group. Total bilirubin in the two groups were decreased, but there was no significant difference between the two groups during the 24-month. The HGB levels and PLT counts in the two groups were increased after 3 months, 6 months, but there was no significant difference between the two groups during the 24-month. No hepatic encephalopathy and spontaneous bacterial peritonitis appeared in the two groups. At the 24 months after transplantation, the ALB, PA and PTA of alcoholic cirrhosis group were still higher than that of the hepatitis B cirrhosis. Conclusion1. BM-MNCs transplantation is safe and effective method for improving liver function, coagulation function and quality of life in decompensated alcohol liver cirrhosis and hepatitis B cirrhosis patients. It also reduces the incidence of serious complications.2. The efficacy of BM-MNCs transplantation in the treatment of decompensated hepatitis B cirrhosis can maintain at least 1 year, we can consider 2 year regular infusion of BM-MNCs for treatment of decompensated hepatitis B cirrhosis. That can improve the patient’s overall conditions.3. Compared decompensated hepatitis B cirrhosis, the efficacy of autologous BM-MNCs transplantation of decompensated alcoholic cirrhosis is improving earlier in the liver function and coagulation function, The time of maintain is longer, and more than 2 years. Patients with alcoholic cirrhosis could prolong the frequency of regular BM-MNCs transplantation.4. BM-MNCs transplantation could provide a new individual therapeutic approach for the treatment of liver cirrhosis. It might represent a routine therapeutic approach to improve the general conditions of decompensated cirrhosis patients.