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

doi:10.3969/j.issn.2095-4344.0463

Abstract

Abstract:

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.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Carcinoma, Hepatocellular, Hepatitis B, Chronic, Liver Cirrhosis, Umbilical Cord, Mesenchymal Stem Cell Transplantation, Tissue Engineering

CLC Number:

R394.2

Ren Hao, Dong Jing, Liu Li-wei, Chen Zhao-lin, Pan Jin-jin, Chen Xi, Song Hai-yan, Zhang Jun-fei, Chen Cong-xin, Liu Bo. Risk factors for hepatocellular carcinoma in hepatitis B cirrhosis patients given treatment with human umbilical cord mesenchymal stem cell[J]. Chinese Journal of Tissue Engineering Research, 2018, 22(9): 1350-1356.

Figures/Tables 2

2.1 研究对象入组流程见图3。 2.2 一般情况共筛选出符合条件的乙型肝炎肝硬化386例完成了随访，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例仅接受常规内科治疗的患者为对照组。两组患者的一般情况、各项指标的基线水平基本一致，见表1。随访至6个月时观察组有7例、对照组有2例患者发生了肝细胞癌(P < 0.05)；12个月时观察组有14例、对照组有6例患者发生了肝细胞癌(P < 0.05)；24个月时观察组有17例、对照组有16例患者发生了肝细胞癌(P > 0.05)；36个月时观察组有20例、对照组有21例患者发生了肝细胞癌(P > 0.05)，见图4。两组内的肝细胞癌患者与非肝细胞癌患者比较，性别、各项生化指标的基线水平以及MELD评分等均与肝细胞癌的发生无关，而在年龄、AFP、AFP-L3、AFP-L3%、GP73等指标上差异有显著性意义(P < 0.05)，见表1。 2.3 肝细胞癌组与非肝细胞癌组发生肝细胞癌危险因素的单因素Logistic回归分析比较单因素分析结果显示：肝细胞癌组患者在接受人脐带间充质干细胞移植治疗前其年龄、AFP、AFP-L3、AFP-L3%、GP73基线水平明显高于非肝细胞癌组，差异有显著性意义(P < 0.05，表2)。 2.4 肝细胞癌组与非肝细胞癌组发生肝细胞癌危险因素的多因素非条件Logistic回归分析比较多因素Logistic回归分析结果显示，AFP-L3%是患者发生肝细胞癌的独立危险因素(P < 0.05，表3)。 2.5 AFP-L3%在预测肝细胞癌中的价值为评价AFP-L3%在接受人脐带间充质干细胞移植的患者中发生肝细胞癌的预测价值，将AFP-L3%检测值分为≥ 10%和< 10%，诊断实验评价见表4；以AFP-L3%≥ 10%作为肝细胞癌的诊断标准，则AFP-L3%诊断肝细胞癌在观察组灵敏度为40%，特异度为98.68%，对照组灵敏度为42.8%，特异度为98.45%。AFP-L3%诊断肝细胞癌的ROC曲线下面积分别为0.956和0.971，见图5。"

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