jianna zhang ¹ Sijie Yu ² Kailu Zhu ³ Shibo Li ² Yu Huang ^1*

• ¹ First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
• ² Zhoushan Hospital Wenzhou Medical University, Zhoushan, Zhejiang Province, China
• ³ Taizhou First People's Hospital, Taizhou, China

Objective: To investigate the probability of hepatocellular carcinoma (HCC) in a large number of grey-zone (GZ) patients with chronic hepatitis B (CHB) in clinical practice. Methods: The patients with CHB who were diagnosed and treated in our hospital from January 2013 to January 2023 were analyzed retrospectively. Results: According to the different levels of HBeAg, ALT and HBV DNA, GZ patients were divided into four categories: 1. Grey zone A (GZ-A): HBeAg positive, normal ALT level, HBV DNA≤10^6 IU/ml; 2. Grey zone B (GZ-B): HBeAg positive, ALT>ULN, HBV DNA≤2×10^4 IU/ml; 3. Grey zone C (GZ-C): HBeAg negative, normal ALT level, HBV DNA≥2×10^3 IU/ml; 4. Grey zone D (GZ-D): HBeAg negative, ALT>ULN, serum HBV DNA≤2×10^3 IU/ml. This observational study showed that after adjustment using inverse probability of treatment weighting (IPTW), the probability of developing HCC in the GZ group was similar to that in the immune-tolerant, HBeAg-positive immune active, and inactive groups. The IPTW-adjusted analysis revealed that the probability of developing HCC in the GZ-B subgroup was similar to that in the immune-active and HBeAg-negative immune-active groups. Conclusion: The GZ group and GZ-B subgroup have a higher risk of HCC. Anti-hepatitis B virus therapy should be considered as early as possible for patients in the GZ group, especially in the GZ-B subgroup.