Zhou Hua-Bang, Li Qiao-Mei, Zhong Zheng-Rong, Hu Jing-Yi, Jiang Xiao-Lan, Wang Hao, Wang Hui, Yang Bing, Hu He-Ping
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.
Am J Cancer Res. 2015 Jan 15;5(2):756-71. eCollection 2015.
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.
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。