The efficacy and long-term safety of autologous bone marrow stem cells transplantation in patients with hepatitis B virus-associated decompensated liver cirrhosis / 中华传染病杂志

ABSTRACT

Objective To evaluate the efficacy and long-term safety of autologous bone marrow stem cells(ABMSC)transplantation in patients with hepatitis B virus(HBV)-associated decompensated liver cirrhosis.Methods This was an open-label,prospective matched case-control study.Thirty patients with HBV-associated decompensated liver cirrhosis hospitalized at the Third Affiliated Hospital of Sun Yat-Sen University from January 2005 to June 2010 were collected and infused with stem cells(stem cell group). Another thirty patients in control group were matched according to baseline characteristics and treated with standard medicine therapy.The patients in stem cell group were treated with stem cells infusion by hepatic artery or portal vein based on standard medicine therapy.All the patients were followed up for 5 to 10 years after surgery. Biochemical indicators were evaluated within the first 48 weeks after transplantation.The complications of cirrhosis and the cumulative incidence rate of hepatocellular carcinoma(HCC)were observed.Measurement data with normal distribution were analyzed by t test. Measurement data with non-normal distribution were compared by Mann-Whitney test.Count data were compared by χ2 test.The cumulative incidence rate of HCC development was compared by Kaplan-Meier analysis.Results The bone marrow aspiration and transplantation surgery were well tolerated in all patients in stem cell group.No complication related to stem cell transplantation therapy was observed. The levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil) and prothrombin time(PT)decreased,albumin level increased,while model for end-stage liver disease (MELD)scores decreased in both groups after treatment.Serum albumin level in stem cell group increased and ALT level decreased markedly at week 4,compared with that in control group at week 4(Z=2.188,P=0.029,Z=3.296,P=0.001,respectively).In stem cell group,21 patients received stem cells transplantation by hepatic artery and 9 patients by portal vein.Biochemical indicators were improved in all patients compared to baseline.However,there was no statistically significant differences between hepatic artery group and portal vein group.The median follow-up time was 6 years.Two patients in stem cell group and 1 patient in control group died(χ2=0.351,P=0.554).Six patients in stem cell group (20.0%)and 11 patients(36.7%)in control group developed HCC.There was no significant differences in the cumulative incidence rate of HCC between two groups(χ2= 0.148,P= 0.701).Hepatorenal syndrome did not development in either group.There were no statistically significant differences in the rates of complications including spontaneous peritonitis,hepatic encephalopathy and gastrointestinal hemorrhage between two groups after 5 to 10 years of follow-up(χ2=0.162,P=0.688,χ2=1.071,P=0.301,χ2=1.071,P=0.301,respectively).Conclusion ABMSC transplantation in patients with HBV-associated decompensated liver cirrhosis improves liver function transiently and has long-term safety.