The "return" of hepatitis B

Area of Science:

• Hepatology
• Virology
• Pharmacology

Background:

• Chronic Hepatitis B virus (HBV) infection treatment has advanced with approved therapies including conventional interferon (IFN), pegylated interferon alfa-2a (PEG IFN alpha2a), lamivudine, adefovir, and entecavir.
• IFN therapy demonstrates higher sustained remission and HBsAg loss rates compared to nucleoside analogues.
• Conventional IFN at lower doses shows comparable efficacy to standard therapy, with longer treatment duration being crucial for remission in HBeAg-negative CHB.

Discussion:

• Pegylated interferon (PEG IFN) is superior to conventional IFN, with no significant dose difference between 90 mcg/wk and 180 mcg/wk in HBeAg-positive patients.
• Nucleoside/nucleotide analogues present challenges such as drug resistance and high relapse rates post-treatment.
• Current antivirals suppress HBV replication but do not eradicate cccDNA, leading to viral relapses after treatment cessation.

Key Insights:

• Longer IFN treatment duration is a significant factor for long-term remission in HBeAg-negative CHB.
• PEG IFN alpha2a is more effective than conventional IFN.
• Realistic treatment goals include durable response, HBeAg clearance, sustained HBV DNA decrease, ALT normalization, improved liver histology, and halted fibrogenesis.

Outlook:

• Further clinical trials are warranted for lower doses of PEG IFN alpha2a in prolonged maintenance or intermittent treatment courses.
• IFN-based therapy can potentially cure liver disease, while nucleotide analogues primarily suppress viral replication and reduce fibrosis.
• Extended treatment durations (≥24 months) with the lowest effective IFN and PEG IFN doses are recommended, alongside further research on nucleoside/nucleotide analogue treatment duration and long-term outcomes.