Zhang Xingxin, Gu Chenjian, Wei Qian, Cao Yirong, She Weimin, Shi Hong, Xie Youhua, Guo Jinsheng
Department of Gastroenterology and Hepatology; Department of Internal Medicine, Shanghai Medical College, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.
Key Laboratory of Medical Molecular Virology, Department of Microbiology and Parasitology, School of Basic Medical Sciences, Fudan University, Shanghai, People's Republic of China.
J Hepatocell Carcinoma. 2023 Apr 11;10:599-609. doi: 10.2147/JHC.S373333. eCollection 2023.
Pre-S1 antigen (pre-S1) is a component of hepatitis B virus large surface antigen (L-HBsAg). This study aimed to investigate the association between clinical pre-S1 antigen (pre-S1) status and adverse prognostic events in chronic hepatitis B (CHB) patients.
This study retrospectively enrolled 840 CHB patients with comprehensive clinical data, including 144 patients with multiple follow-up of pre-S1 status. All patients were tested for serum pre-S1 and divided into pre-S1 positive and negative groups. Single factor and logistic multiple regression analyses were performed to explore the association between pre-S1 and other HBV biomarkers with the risk of hepatocellular carcinoma (HCC) in CHB patients. The pre-S1 region sequences of HBV DNA were obtained from one pre-S1 positive and two pre-S1 negative treatment-naïve patients using polymerase chain reaction (PCR) amplification followed by Sanger sequencing.
The quantitative HBsAg level was significantly higher in the pre-S1 positive group than that in the pre-S1 negative group (Z=-15.983, <0.001). The positive rate of pre-S1 increased significantly with the increase in HBsAg level ( =317.963, P<0.001) and HBV DNA load ( =15.745, <0.001). The pre-S1 negative group had a higher HCC risk than the pre-S1 positive group (Z=-2.00, =0.045, OR=1.61). Moreover, patients in the sustained pre-S1 negative group had a higher HCC risk (Z=-2.56, =0.011, OR=7.12) than those in the sustained pre-S1 positive group. The sequencing results revealed mutations in the pre-S1 region from samples of pre-S1 negative patients, including frameshift and deletion mutations.
Pre-S1 is a biomarker that indicates the presence and replication of HBV. Pre-S1 sustained negativity attributed to pre-S1 mutations in CHB patients may be associated with a higher risk of HCC, which has clinical significance and warrant further investigations.
前S1抗原（pre-S1）是乙型肝炎病毒大表面抗原（L-HBsAg）的一个组成部分。本研究旨在探讨慢性乙型肝炎（CHB）患者临床前S1抗原（pre-S1）状态与不良预后事件之间的关联。
本研究回顾性纳入了840例具有全面临床资料的CHB患者，其中144例患者对pre-S1状态进行了多次随访。所有患者均检测血清pre-S1，并分为pre-S1阳性组和阴性组。进行单因素和逻辑多元回归分析，以探讨pre-S1和其他HBV生物标志物与CHB患者肝细胞癌（HCC）风险之间的关联。使用聚合酶链反应（PCR）扩增，随后进行桑格测序，从1例pre-S1阳性和2例未接受过治疗的pre-S1阴性患者中获取HBV DNA的pre-S1区域序列。
pre-S1阳性组的定量HBsAg水平显著高于pre-S1阴性组（Z = -15.983，P < 0.001）。随着HBsAg水平的升高（χ² = 317.963，P < 0.001）和HBV DNA载量的升高（χ² = 15.745，P < 0.001），pre-S1的阳性率显著增加。pre-S1阴性组的HCC风险高于pre-S1阳性组（Z = -2.00，P = 0.045，OR = 1.61）。此外，持续pre-S1阴性组患者的HCC风险（Z = -2.56，P = 0.011，OR = 7.12）高于持续pre-S1阳性组患者。测序结果显示pre-S1阴性患者样本的pre-S1区域存在突变，包括移码突变和缺失突变。
pre-S1是一种指示HBV存在和复制的生物标志物。CHB患者中由于pre-S1突变导致的pre-S1持续阴性可能与较高的HCC风险相关，这具有临床意义，值得进一步研究。
