人脐带间充质干细胞治疗乙型肝炎肝硬化患者发生肝细胞癌的危险因素分析

Risk factors for hepatocellular carcinoma in hepatitis B cirrhosis patients given treatment with human umbilical cord mesenchymal stem cells

背景:随着间充质干细胞治疗的不断发展,相关文献报道干细胞治疗可能会导致肿瘤的发生发展。目的:了解人脐带间充质干细胞移植治疗乙型肝炎肝硬化患者发生肝细胞癌的潜在风险。方法:收集2011年1月至2013年12月在解放军第一○五医院感染病科住院治疗的乙型肝炎肝硬化患者,随访36个月,终点为确诊肝细胞癌。对可能影响肝细胞癌发生的相关危险因素进行单因素Logistic和多因素非条件Logistic回归分析。结果与结论:(1)386例患者完成随访,其中171例接受人脐带间充质干细胞治疗的患者为观察组,215例仅接受常规内科综合治疗的患者为对照组;(2)随访12个月时,观察组肝细胞癌的发病率明显高于对照组(P<0.05),随访36个月时,观察组肝细胞癌的发生率为11.7%,对照组为9.8%(P>0.05);(3)单因素Logistic回归分析显示观察组和对照组内肝细胞癌患者在年龄、甲胎蛋白(AFP)、甲胎蛋白异质体(AFP-L3)、甲胎蛋白异质体比率(AFP-L3%)、高尔基体糖蛋白73(GP73)等方面均显著高于非肝细胞癌患者(P<0.05),多因素非条件Logistic回归分析显示仅甲胎蛋白异质体比率是人脐带间充质干细胞治疗后乙型肝炎肝硬化患者发生肝细胞癌的独立危险因素;(4)结果表明,人脐带间充质干细胞治疗不会导致乙型肝炎肝硬化患者3年内肝细胞癌总发病率的上升,但可能会引起肝细胞癌发病时间的提前;甲胎蛋白异质体比率可作为人脐带间充质干细胞治疗后乙型肝炎肝硬化患者发生肝细胞癌的早期预测指标。

BACKGROUND:With the continuous development of mesenchymal stem cell therapy,it has been reported that stem cell therapy is likely to cause the occurrence and development of tumors.OBJECTIVE:To investigate the potential risks of hepatocellular carcinoma(HCC)in patients with hepatitis B cirrhosis after receiving human umbilical cord mesenchymal stem cells(hUC-MSCs)transplantation.METHODS:The study collected the information of patients with hepatitis B cirrhosis treated with hUC-MSCs,admitted at the Infectious Disease Department of the 105th Hospital of PLA from January 2011 to December 2013.The following investigation lasted 36 months.The follow-up was terminated at the time of diagnostic confirmation.The risk factors that may affect the occurrence of HCC were analyzed by univariate Logistic and multivariate unconditional Logistic regression analyses.RESULTS AND CONCLUSION:(1)A total of 386 patients were followed up,including 171 patients who received hUC-MSCs transplantation as the observation group and 215 patients only given general internal medicine treatment as the control group.(2)At the follow-up of 12 months,the incidence of HCC in the observation group was significantly higher than that in the control group(P<0.05).At the follow-up of 36 months,the incidence of HCC was 11.7%in the observation group and 9.8%in the control group(P>0.05).(3)Univariate Logistic regression analysis showed that the HCC patients had higher age,alpha-fetoprotein(AFP),alpha-fetoprotein variants(AFP-L3),AFP-L3 ratio(AFP-L3%),and Golgi glycoprotein 73(GP73)than those with no HCC in both control and observation groups(P<0.05).Multivariate unconditional Logistic regression analysis showed that only APF-L3%was an independent risk factor for HCC in patients with hepatitis B cirrhosis undergoing hUC-MSCs transplantation.Overall,hUC-MSCs transplantation does not increase the HCC incidence in patients with hepatitis B cirrhosis within 3 years,but it may lead to an early onset of HCC.AFP-L3%can be used as an early predictor of HCC in patients with hepatitis B cirrhosis undergoing hUC-MSCs transplantation.