摘要
目的探讨自体骨髓干细胞在失代偿期乙型肝炎肝硬化患者中应用的疗效及长期安全性。
方法本临床试验为开放性、前瞻性配对研究。选取2005年1月至2010年6月期间中山大学附属第三医院感染科住院的30例失代偿期乙型肝炎肝硬化患者进行干细胞治疗（干细胞组），根据基线匹配30例患者为对照组。对照组患者给予内科综合治疗。干细胞组患者在内科综合治疗基础上，经肝动脉或门静脉行自体骨髓干细胞移植术。术后随访5～10年。监测移植后48周内两组患者生物化学指标，观察两组患者肝硬化并发症、肝细胞癌（hepatocellular carcinoma，HCC）累积发生率。符合正态分布的计量资料采用t检验，非正态分布的计量资料采用Mann-Whitney检验，计数资料采用χ2检验；HCC累积发生率采用生存分析Kaplan-Meier法计算。
结果干细胞组患者都能耐受骨髓采集和干细胞移植术，未观察到移植相关并发症。治疗后，两组患者ALT、AST、TBil水平下降，PT缩短，白蛋白升高，终末期肝病模型评分降低。同对照组相比，治疗4周时干细胞组患者白蛋白水平明显升高（Z＝2.188，P＝0.029），ALT显著下降（Z＝3.296，P＝0.001）。干细胞组30例患者中，21例经肝动脉移植，9例经门静脉移植，移植后两组患者生化指标均较基线有改善，组间比较差异均无统计学意义。中位随访时间6年，干细胞组2例患者死亡，对照组1例死亡（χ2＝0.351, P＝0.554）。干细胞组6例发生HCC（20.0%），对照组11例（36.7%），两组肝细胞癌累积发生率差异无统计学意义（χ2＝0.148, P＝0.701）。两组患者随访期间均未出现肝肾综合征。两组患者肝硬化并发症如自发性腹膜炎、肝性脑病、消化道出血发生率差异均无统计学意义（χ2值分别为0.162、1.071和1.071，P值分别为0.688、0.301和0.301）。
结论自体骨髓干细胞应用于失代偿期乙型肝炎肝硬化患者短期内有效，长期安全性良好。
ObjectiveTo 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.
MethodsThis 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.
ResultsThe 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）.
ConclusionABMSC transplantation in patients with HBV-associated decompensated liver cirrhosis improves liver function transiently and has long-term safety.
出处
《中华传染病杂志》
CSCD
北大核心
2017年第12期719-724,共6页
Chinese Journal of Infectious Diseases
关键词
肝硬化
移植
骨髓干细胞
Liver cirrhosis
Transplantation
Bone marrow stem cells
