| Background Acute-on-chronic liver failure (ACLF) caused by hepatitis B virus(HBV) is a severe disease with high mortality. Liver transplantation is the onlytherapy that had been proven beneficial, but the rapidity of progression and variablecourse of ACLF limit it application, and effective use of this limited resource requiresaccurate prognostication and subsequent lifelong immunosuppression. Antiviraltreatment contributed to the improved outcomes, but its mortality was still more than50%. So it is necessary to find a safe, effective and convenient method.Bone marrow mesenchymal stem cells (BM-MSCs) are characterized by theproperties of self-renewal and multipotentiality. The previous studies showed thatBM-MSCs performed the abilities of homing to the damaged liver, differentiating intohepatocytes, inhibiting the progress of liver fibrosis and having no tumorigenicity invitro. Besides, BM-MSCs possess the properties of low immunogenicity andimmunomodulatory. Clinically, BM-MSCs were used in the immunosuppressivetreatment after organ transplantation and in the steroid-resistant, severeGraft-versus-host reaction (GvHD), which were proven effectively. Our early studyrevealed that autologous bone marrow mesenchymal stem cells (BM-MSCs)transplantation for liver failure patients caused by hepatitis B improves liver functions,but without any survival benefit. The inadequate BM-MSCs dose for transfusion maybe the main cause for it. In view of the factors mentioned above, we administrate thepatients with ACLF related with hepatitis B with two different doses of allogeneicBM-MSCs via peripheral veins for4times, in order to investigate the safety andefficacy of this therapy.Aims This study aimed to assess the safety and efficacy of allogeneic BM-MSCstransplantation via peripheral veins for the patients with ACLF caused by hepatitis B by increasing BM-MSCs dose and transplantating frequence.Methods Twenty five inpatients with ACLF related with HBV were divided into3groups randomly. Group SMT received the standard medicine treatment. GroupMSC-1and Group MSC-2underwent transplantations of allogeneic BM-MSCs1×10~5/Kg and1×10~6/Kg by peripheral veins once a week for4weeks respectively, inaddition to the standard medicine treatment. Group MSC were defined as thecombined of Group MSC-1and MSC-2. All the groups were followed up for24weeks.Results No serious adverse reactions were observed from1-24weeks aftertransplantations. There were no significant differences in the levels of white bloodcells (WBC), hemoglobin (Hb) and platelet (PLT) at1-4weeks after transplantationamong the3groups. And no dramatic differences were found in the levers ofcreatinine (Cr) among the3groups from1-24weeks. There was no patient developinghepatocellular carcinoma (HCC) or tumors originated from other organs. Comparingwith Group SMT, Group MSC achieved higher24-week cumulative survival rate(P=0.020), and Group MSC acquired markedly improvements in liver functions from1to4weeks after transplantations. There were no significant differences in theincidence of complications (i.e., infection, encephalopathy, hepatorenal syndrome,gastrointestinal bleeding, and toxic enteroparalysis) from1-24weeks aftertransplantations between Group SMT and Group MSC. The lever of alanineaminotransferase (ALT) of patients in Group MSC-2was markedly improved at week1and2after transplantation (P value were0.011,0.013respectively), compared withGroup MSC-1. However, Group MSC-1got dramatic improvement in levers of Modelfor End-Stage Liver Disease (MELD) score at week4(P=0.048). There were nosignificant differences in24-week cumulative survival rates and the incidence ofcomplications between Group MSC-1and Group MSC-2. Conclusion Allogeneic BM-MSCs transplantation via peripheral veins is safe foracute-on-chronic liver failure patients caused by hepatitis B. It can improve the liverfunctions and24-week survival rate. There were no significant differences in theefficacy between Group MSC-1and Group MSC-2. |
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