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Volume 41 Issue 12
Dec.  2025
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Article Navigation >  Journal of Clinical Hepatology  > 2025  >  41(12): 2506-2511

Efficacy of combined versus sequential antiviral therapy in HBeAg-negative chronic hepatitis B patients achieving incomplete virological response during initial antiviral therapy

DOI: 10.12449/JCH251211

  • Department of Liver Diseases，The 980th Hospital of PLA Joint Logistics Support Force，Shijiazhuang 050082，China

Research funding:

Medical Science Research Project of Hebei (20240328)

More Information
  • Corresponding author: KANG Fubiao， kangfb@hebmu.edu.cn （ORCID： 0000-0002-9945-8657）
  • Received Date: 2025-05-21
  • Accepted Date: 2025-07-25
  • Published Date: 2025-12-25
    Abstract
  •   Objective  To investigate the efficacy and safety of combined versus sequential antiviral regimens in HBeAg-negative chronic hepatitis B （CHB） patients achieving incomplete virological response during initial antiviral therapy， and to provide evidence for clinical practice.  Methods  A total of 117 HBeAg-negative CHB patients who attended The 980th Hospital of PLA Joint Logistics Support Force from January 2020 to December 2023 and met the criteria for incomplete virological response were enrolled， and according to the clinical treatment regimen， they were divided into combination group （the original antiviral agent combined with another type of drug） and sequential group （switching to a new drug）. The primary outcome measure was HBV DNA clearance rate at weeks 4， 12， 24， and 48 of combined or sequential therapy， and the secondary outcome measures were alanine aminotransferase （ALT） normalization rate， renal function， myocardial enzymes， and blood lipid profiles. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the chi-square test and the Fisher’s exact test were used for comparison of categorical data between two groups.  Results  Among the 117 CHB patients， there were 49 patients in the combination group and 68 patients in the sequential group. At weeks 24 and 48 of combined or sequential therapy， the combination group had a significantly higher HBV DNA clearance rate than the sequential group （week 24： 95.92% vs 80.88%， χ2=5.761， P=0.016； week 48： 97.96% vs 86.76%， χ2=4.566， P=0.044）. Compared with the sequential group， the combination group showed a significantly higher level of viral inhibition in patients with a high viral load （HBV DNA ≥104 IU/mL） （week 12： 73.33% vs 19.05%， χ2=10.609， P=0.002； week 24： 86.67% vs 47.62%， χ2=5.783， P=0.033）. There was no significant difference in treatment outcome between the two groups among the patients with a low viral load （P>0.05）. The combination group had an ALT normalization rate of 65.31%， 89.80%， 81.63%， and 95.92%， respectively， at 4， 12， 24， and 48 weeks， while the sequential group had an ALT normalization rate of 54.41%， 89.71%， 86.76%， and 94.12%， respectively； there were no significant differences between the two groups （all P>0.05）. There were no abnormalities in renal function， myocardial enzymes， and blood lipids in either group within 48 weeks of combined or sequential therapy.  Conclusion  In HBeAg-negative CHB patients with incomplete virological response， combination therapy has significantly better efficacy than sequential therapy in the high viral load subgroup and can achieve virological suppression more rapidly， and the two regimens have similar efficacy in patients with a low viral load. Both combined and sequential therapies have a favorable safety profile.

     

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