The Efficiency Of Autologous Bone Marrow-Derived Mononuclear Cells Transplantation In Patients With Decompentsated Liver Cirrhosis

Background and ObjectiveBecause of the high incidence and mortality,liver cirrhosis has been the medical problems for many years.At present, liver transplantation is the only effective treatment for these patients,however,due to the various aspects of restrictive,it didn’t brought hopes for the patients with liver cirrhosis. In recent years, as the progress of basic researches in stem cells,the experimental studies of stem cell therapy in rodent models of cirrhosis have shown encouraging results,and the clinical trails have demonstrated the safety and feasibility of stem cells infusion in patients with cirrhosis. The application of stem cells in hepatology has got more and more attentions, and that must become a new hope for patients with liver cirrhosis.The purpose of this study is to assess the effect in the patients with decompensated cirrhosis,after autologous transplantation of bone marrow-derived mononuclear cells.Materials and MethodsWe prospectively enrolled65patients who hospitalized in the department of gastroenterology at Henan province people’s hospital.Eligible patients were between18and75years of age with a clinical and imaging diagnosis of cirrhosis (different causes of cirrhosis were accepted) furthermore the value of alpha fetal protein must be normal,no hepatocellular carcinoma was observed in the khepatic arteriography.Patients were excluded from the study if they had insufficiency in cardio-pulmonary,any disease of hematological system,malignancies in other organs,human immunodeficiency virus(HIV),the presence of active or chronic thrombosis of the portal or hepatic veins,any type of systemic infection,refractory ascites,active variceal bleeding,hepatic encephalopathy,and any other severe complications.80ml-100ml of autologous bone marrow was aspirated from the iliac cres under local anesthesia.Bone marrow-derived mononuclear cells were isolated under aseptic conditions,the cells were finally resuspended in40ml of saline,then the cell suspension was infused via the hepatic artery.The clinical and laboratory evaluation were performed at days0and7;months1,3,6,12and24post-transplantation for long-term follow up.liver function tests,blood routine examinations,coagulation profile,and abdominal ultrasound.Repeated measures analysis of variance was used for the quantitative data to determine the efficacy of cell therapy, all measurement data were expressed as mean±SD.Result(1)65patients with decompentsated liver cirrhosis were recruited into the study,but four didn’t complete the follow-up period so were subsequently excluded.Thus,a total of61patients were followed up to the end in the study,35male and26female,their age ranged from24to67years.mean51.02years.The etiology of liver cirrhosis was different,the majority of patients had hepatitis B(49cases),others were hepatitis C(6cases),alcoholic(l case),autoimmune liver disease(4cases),cyptogenic(l case).(2)The volume of bone marrow aspirated from the iliac crest of the patients was100ml,the number of viable mononuclear cells transplanted into the patients’liver was (1.47-9.92)×10~9,the rate of viability of the mononuclear cells was93%-99%.(3) There were no adverse reactions in the patients during the12months after cells transplantation,their clinical signs and symptoms improved obviously, the liver cancer had not been occurred under the color ultrasonography, ascites regeneration significantly reduced.1year later, there were four patients hospitalized again, accounting for6.56%of all the patients who had received cells transplantation.(4) Laboratory Data:①The liver function test results indicate, serum albumin and former albumin had a significantly increase a month after cells were infused, and can last for two years and with no signs of reducing,ALT and AST had no change in the12months after cells infused (P>0.05), the testing results showed that ALT and AST had a significant reduction24months after cells infused(P<0.05),The evel of serum total bilirubin1(TBIL) reduced significantly in the testing results of the12and24monthes after cells infused (P<0.05);②TThe blood routine testing results indicate,the number of platelet (PLT) and white blood cells (WBC) increased gradually in the24months after the infusion of cells,the testing results had increased significantly in the12months testing(P<0.05),the number of red blood cells and the amount of hemoglobin had no significant changes (P>0.05);③Blood clotting testing results indicate:activated parttial thrombomboplatin time (APTT) gradually shortened after infusion of cells, it showed significant changes in the testing results of the12th and the24th months tests (P<0.05), Fibrinogen (FIB) had increased significantly3months after infusion,and increased to normal gradually in the24months (P<0.05),there were no significant changes of prothrombin time (PT), thrombin time (TT) and the international standardization ratio (INR)(P>0.05).ConclusionOur data has shown that transplantation of autologous bone marrow-derived mononuclear cells can result in a long-term improvement of liver function in patients with Decompentsated Liver Cirrhosis, and may become a modality in the treatment of decompensated liver cirrhosis.