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Comparison of clinical practice guidelines for chronic hepatitis B: natural history classification and treatment

Gi-Ae Kim1, Won-Mook Choi2, Gwang Hyeon Choi3

  • 1Department of Internal Medicine, College of Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, Korea.

Clinical and Molecular Hepatology
|June 29, 2026
PubMed

Insights

New chronic hepatitis B (CHB) guidelines offer updated approaches to patient management. The Korean Association for the Study of the Liver-East Asia Liver Alliance (KASL-EALA) guideline simplifies treatment decisions by focusing on HBV DNA levels, while others retain traditional classifications.

Area of Science:

  • Hepatology
  • Virology
  • Clinical Practice Guidelines

Background:

  • Clinical practice guidelines (CPGs) for chronic hepatitis B (CHB) are periodically updated to reflect new evidence.
  • Recent updates from major international and regional bodies (KASL-EALA, AASLD, EASL, WHO) address CHB natural history, treatment initiation, and antiviral selection.
  • Managing CHB patients, particularly those in the indeterminate or "grey zone" phase, remains complex.

Purpose of the Study:

  • To compare the latest major CPGs for CHB management.
  • To highlight key differences and similarities in natural history classification, treatment indications, and antiviral agent selection.
  • To inform clinicians and guide future harmonization efforts in CHB care.

Main Methods:

  • Comparative review of recent CPGs from KASL-EALA (2026), AASLD (2025), EASL (2025), and WHO (2024).
  • Focus on changes in classification of CHB natural history, criteria for initiating antiviral therapy, and choices of antiviral medications.
  • Analysis of how each guideline addresses the challenges of the indeterminate phase and treatment decision-making.

Main Results:

  • KASL-EALA 2026 introduces a novel framework based on HBV DNA levels, removing the indeterminate category to better correlate with hepatocellular carcinoma (HCC) risk and simplify treatment decisions.
  • AASLD 2025, EASL 2025, and WHO 2024 maintain traditional immunological phase-based classifications for natural history.
  • All guidelines support expanded access to antiviral therapy, with AASLD emphasizing shared decision-making, EASL focusing on individualized risk assessment, and WHO 2024 removing phase-based criteria for treatment decisions.

Conclusions:

  • Significant divergence exists among recent CHB guidelines, particularly in natural history classification and treatment decision frameworks.
  • The KASL-EALA guideline represents a notable shift towards simplifying management based on viral load.
  • Understanding these variations is crucial for clinicians to optimize patient care and contributes to the ongoing global effort to harmonize CHB management strategies.

Keywords:
Chronic hepatitis BGuidelinesNatural historyTreatment

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