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Area of Science:

  • Hepatology
  • Virology
  • Immunology

Background:

  • Chronic hepatitis B (CHB) treatment with nucleos(t)ide analogues (NUCs) and interferon has limitations.
  • NUCs provide viral suppression but often lead to off-therapy relapses, necessitating long-term treatment.
  • Interferon offers finite treatment duration and potential viral eradication by modulating immune responses.

Purpose of the Study:

  • To review and categorize current combination therapy strategies for CHB.
  • To evaluate the efficacy and outcomes of different NUC and interferon combination approaches.
  • To identify predictive markers for successful combination therapy in CHB patients.

Main Methods:

  • Systematic review of simultaneous "dual" therapy, sequential "add-on" therapy, and "switch" therapy strategies.
  • Comparison of combination therapies against NUC or interferon monotherapy.
  • Analysis of on-treatment and off-therapy viral suppression, drug resistance, and sustained virological responses.

Main Results:

  • Dual therapy demonstrated superior on- and off-therapy viral suppression and reduced drug resistance compared to NUC monotherapy.
  • Dual therapy showed enhanced on-treatment suppression versus interferon monotherapy, with similar off-therapy sustained responses.
  • Specific add-on or switch strategies showed promise for on-treatment efficacy in certain patient groups.

Conclusions:

  • Combination therapy with NUCs and interferon presents a promising strategy for CHB management.
  • Predictive markers like quantitative hepatitis B surface antigen and e antigen levels are crucial for tailoring treatment.
  • Further research is needed to optimize combination regimens and personalize CHB therapy schedules.