Hepatocellular carcinoma among patients with chronic hepatitis B in the indeterminate phase

Area of Science:

• Hepatology
• Virology
• Oncology

Background:

• Hepatitis B virus (HBV) infection progresses through defined stages, but some patients enter an 'indeterminate phase' lacking clear classification.
• This indeterminate phase, potentially affecting up to 50% of HBV patients, is characterized by ambiguous biomarker levels.
• Definitions of this phase vary across guidelines due to differing biomarker cut-offs.

Purpose of the Study:

• To review key data on patients in the indeterminate phase of HBV infection.
• To emphasize the association between the indeterminate phase and an increased risk of hepatocellular carcinoma (HCC).
• To examine the potential role of antiviral therapy in reducing HCC risk in this patient group.

Main Methods:

• Review of clinical data linking indeterminate phase patients to increased HCC risk.
• Analysis of molecular evidence, including HBV-DNA integration and immune activation.
• Holistic approach integrating biological data, clinical observations, and treatment outcomes.

Main Results:

• Patients in the indeterminate phase exhibit molecular evidence of hepatocarcinogenesis despite normal liver enzymes.
• HBV-DNA integration into the host genome and immune activation are observed in this group.
• Antiviral therapy has demonstrated a reduction in fibrosis and HCC risk.

Conclusions:

• The indeterminate phase of HBV infection presents significant risks, particularly for HCC development.
• Antiviral therapy offers a strategy to mitigate these risks by targeting underlying mechanisms.
• Further consideration of antiviral therapy is crucial for managing residual HCC risk in indeterminate phase patients.