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乙肝表面抗原水平可能作为预测低病毒载量患者根治性切除术后肝细胞癌复发的新标志物。

Level of hepatitis B surface antigen might serve as a new marker to predict hepatocellular carcinoma recurrence following curative resection in patients with low viral load.

作者信息

Zhou Hua-Bang, Li Qiao-Mei, Zhong Zheng-Rong, Hu Jing-Yi, Jiang Xiao-Lan, Wang Hao, Wang Hui, Yang Bing, Hu He-Ping

机构信息

Department of Hepatobiliary I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University Shanghai, China.

Department of Laboratory, First Affiliated Hospital, Bengbu Medical College Anhui, China.

出版信息

Am J Cancer Res. 2015 Jan 15;5(2):756-71. eCollection 2015.

Abstract

To investigate the association between preoperative HBsAg (hepatitis B surface antigen) level and risk of HCC (hepatocellular carcinoma) recurrence following curative resection, we enrolled 826 HBV-related HCC patients who underwent curative resection and received long-term follow-up at the Eastern Hepatobiliary Surgery Hospital (Shanghai, China). Multivariate analyses showed that serum HBsAg ≥ 2000 S/CO, seropositive hepatitis B e antigen (HBeAg), γ-glutamyl transpeptidase > 61 U/L, prothrombin time > 13 s, multinodularity, lager tumor size, and major portal vein invasion were independently associated with a increased risk of HCC recurrence. Compared with HCC patients with HBsAg level < 2000 S/CO, HCC patients with HBsAg level ≥ 2000 S/CO had a higher prevalence of seropositive HBeAg, antiviral therapy, and cirrhosis; were younger; and had a higher levels of alanine transaminase (ALT), aspartate aminotransferase (AST), and HBV viral load. Multivariable stratified analyses showed HCC patients with HBsAg level < 2000 S/CO tended to have a lower incidence of HCC recurrence in following subgroups of patients, including for noncirrhotic (HR, 0.561; 95% CI, 0.345-0.914), HBV DNA < 2000 IU/mL (HR, 0.604; 95% CI, 0.401-0.912), ALT ≤ 41 U/L (HR, 0.643; 95% CI, 0.440-0.942), AST ≤ 37 U/L (HR, 0.672; 95% CI, 0.459-0.983), and seronegative HBeAg (HR, 0.682; 95% CI, 0.486-0.958). When we evaluated HBeAg-negative patients with HBV DNA < 2000 IU/mL, HBsAg level still determined risk of HCC recurrence (p = 0.014), but not HBV DNA (p = 0.550) and ALT (p = 0.186). These results suggest high levels of HBsAg increase risk of HCC recurrence following curative resection. HBsAg level might serve as a new marker to complement HBV DNA level in predicting HCC recurrence, especially in HBeAg-negative patients with low viral load.

摘要

为了研究术前乙肝表面抗原(HBsAg)水平与根治性切除术后肝细胞癌(HCC)复发风险之间的关联,我们纳入了826例在东方肝胆外科医院(中国上海)接受根治性切除并接受长期随访的HBV相关HCC患者。多因素分析显示,血清HBsAg≥2000 S/CO、乙肝e抗原(HBeAg)血清学阳性、γ-谷氨酰转肽酶>61 U/L、凝血酶原时间>13 s、多结节性、肿瘤较大以及门静脉主干侵犯与HCC复发风险增加独立相关。与HBsAg水平<2000 S/CO的HCC患者相比,HBsAg水平≥2000 S/CO的HCC患者HBeAg血清学阳性、抗病毒治疗和肝硬化的患病率更高;年龄更小;丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)和HBV病毒载量水平更高。多变量分层分析显示,在以下患者亚组中,HBsAg水平<2000 S/CO的HCC患者HCC复发发生率往往较低,包括非肝硬化患者(风险比[HR],0.561;95%置信区间[CI],0.345 - 0.914)、HBV DNA<2000 IU/mL患者(HR,0.604;95% CI,0.401 - 0.912)、ALT≤41 U/L患者(HR,0.643;95% CI,0.440 - 0.942)、AST≤37 U/L患者(HR,0.672;95% CI,0.459 - 0.983)以及HBeAg血清学阴性患者(HR,0.682;95% CI,0.486 - 0.958)。当我们评估HBV DNA<2000 IU/mL的HBeAg阴性患者时,HBsAg水平仍然决定HCC复发风险(p = 0.014),而HBV DNA(p = 0.550)和ALT(p = 0.186)则不然。这些结果表明,高水平的HBsAg会增加根治性切除术后HCC复发的风险。HBsAg水平可能作为一种新的标志物,在预测HCC复发方面补充HBV DNA水平,尤其是在病毒载量低的HBeAg阴性患者中。

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