Hepatitis B surface antigen glycan isomer is a predictor of the development of hepatocellular carcinoma during nucleoside/nucleotide analog therapy

• Published in: Hepatology research 2024-07, Vol.54 (7), p.615-626
• Main Authors: Kozuka, Ritsuzo, Enomoto, Masaru, Yukawa‐Muto, Yoshimi, Odagiri, Naoshi, Kotani, Kohei, Motoyama, Hiroyuki, Kawamura, Etsushi, Hagihara, Atsushi, Fujii, Hideki, Uchida‐Kobayashi, Sawako, Kawada, Norifumi
• Format: Article
• Language: English
• Subjects: Antigens; Genotypes; Hepatitis B; Hepatitis B surface antigen; hepatitis B surface antigen glycan isomer; Hepatocellular carcinoma; Liver cancer; Monoclonal antibodies; Multivariate analysis; Nucleoside analogs; nucleoside/nucleotide analog; Nucleotide analogs
• ISSN: 1386-6346; 1872-034X
• DOI: 10.1111/hepr.14016

Aim A recombinant monoclonal antibody against the hepatitis B surface antigen glycan isomer (HBsAgGi) was newly developed using the O‐glycosylated PreS2 peptide in M‐HBsAg of hepatitis B virus (HBV) genotype C. However, the association between HBsAgGi and the development of hepatocellular carcinoma (HCC) during nucleoside/nucleotide analog (NA) therapy remains unknown. Methods A total of 112 HBV genotype C‐infected patients who were treated with NA were included in this study. We assessed the association between HBV markers, including HBsAgGi and other conventional markers, and the development of HCC during NA therapy. Results Ten patients developed HCC during the follow‐up period. Of the HBV markers, HBsAg (≤3.53 log IU/mL; p = 0.047), HBsAgGi/HBsAg ratio (≥1.10; p = 0.035), and HBV DNA (≤6.3 log copies/mL; p = 0.012) at baseline and HBsAg (≤3.19 log IU/mL; p = 0.033) and HBsAgGi/HBsAg ratio (≥1.09; p = 0.003) at 48 weeks after NA therapy were significantly associated with the development of HCC according to the log rank test. In contrast, no significant association was observed between HBsAgGi and the development of HCC. Multivariate analysis revealed that a platelet count at baseline ≤88 × 103/mm3 (p = 0.026; hazard ratio [HR], 10.577) and an HBsAgGi/HBsAg ratio at 48 weeks after NA therapy ≥1.09 (p = 0.040; HR, 10.099) were independently and significantly associated with the development of HCC. Conclusions Our findings suggest that a combination of on‐treatment HBsAgGi and HBsAg predicts the development of HCC during NA therapy. The baseline platelet count and on‐treatment hepatitis B surface antigen glycan isomer/hepatitis B surface antigen (HBsAgGi/HBsAg) ratio were useful predictors of hepatocellular carcinoma (HCC) development during nucleoside/nucleotide analog (NA) therapy. In addition, it suggests that a combination of on‐treatment HBsAgGi and HBsAg may lead to an increase in the accuracy of predictions of the development of HCC during NA therapy compared with HBsAg alone.