Journal of Hepatocellular Carcinoma (Apr 2023)

Pre-S1 Mutations as Indicated by Serum Pre-S1 Antigen Negative is Associated with an Increased Risk of Hepatocellular Carcinoma in Chronic Hepatitis B Patients

  • Zhang X,
  • Gu C,
  • Wei Q,
  • Cao Y,
  • She W,
  • Shi H,
  • Xie Y,
  • Guo J

Journal volume & issue
Vol. Volume 10
pp. 599 – 609

Abstract

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Xingxin Zhang,1 Chenjian Gu,2 Qian Wei,1 Yirong Cao,1 Weimin She,1 Hong Shi,1 Youhua Xie,2 Jinsheng Guo1 1Department of Gastroenterology and Hepatology; Department of Internal Medicine, Shanghai Medical College, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 2Key Laboratory of Medical Molecular Virology, Department of Microbiology and Parasitology, School of Basic Medical Sciences, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Jinsheng Guo, Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai, 200032, People’s Republic of China, Tel +86 21-64041990 ext. 2424, Fax +86 21 64038472, Email [email protected] Youhua Xie, Department of Microbiology and Parasitology, School of Basic Medical Sciences, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People’s Republic of China, Tel +86 13651772272, Email [email protected]: 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.Methods: 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.Results: The quantitative HBsAg level was significantly higher in the pre-S1 positive group than that in the pre-S1 negative group (Z=− 15.983, P< 0.001). The positive rate of pre-S1 increased significantly with the increase in HBsAg level (χ2=317.963, P< 0.001) and HBV DNA load (χ2=15.745, P< 0.001). The pre-S1 negative group had a higher HCC risk than the pre-S1 positive group (Z=− 2.00, P=0.045, OR=1.61). Moreover, patients in the sustained pre-S1 negative group had a higher HCC risk (Z=− 2.56, P=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.Conclusion: 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.Keywords: chronic hepatitis B, pre-S1 antigen, hepatocellular carcinoma

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