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Lamivudine resistance in children with chronic hepatitis B

Erhun Kasırga1

  • 1Erhun Kasırga, Department of Pediatric Gastroenterology, Celal Bayar University, 45030 Manisa, Turkey.

World Journal of Hepatology
|May 5, 2015
PubMed

Insights

Lamivudine (LAM) is a first-line treatment for chronic hepatitis B (CHB) in children, but its low genetic barrier leads to frequent viral resistance and relapse. A more potent antiviral drug with a higher genetic barrier is needed for effective CHB management.

Area of Science:

  • Hepatology
  • Virology
  • Pediatric Infectious Diseases

Background:

  • Chronic hepatitis B (CHB) in children currently relies on interferon-alpha and lamivudine (LAM) as first-line treatments.
  • LAM effectively inhibits hepatitis B virus (HBV) DNA polymerase but has limitations including inability to eradicate covalently closed circular DNA, leading to frequent relapses.
  • LAM's low genetic barrier contributes to viral resistance, emergence of YMDD motif mutants, and potential cross-resistance, diminishing efficacy of subsequent therapies.

Purpose of the Study:

  • To highlight the limitations of lamivudine (LAM) as a first-line treatment for chronic hepatitis B (CHB) in children.
  • To emphasize the need for alternative antiviral therapies with higher genetic barriers to resistance.
  • To discuss the implications of LAM resistance, including diminished efficacy of other antivirals and potential vaccine escape mutants.

Main Methods:

  • Literature review and analysis of existing data on lamivudine efficacy and resistance in pediatric CHB.
  • Examination of the mechanisms of HBV replication inhibition and resistance development associated with LAM.
  • Assessment of the clinical impact of LAM resistance on treatment outcomes and vaccine effectiveness.

Main Results:

  • Lamivudine (LAM) exhibits a low genetic barrier, frequently leading to the selection of YMDD motif mutants and viral resistance.
  • Viral breakthrough and biochemical breakthrough are common consequences of insufficient viral suppression by LAM.
  • LAM resistance can reduce the effectiveness of other antiviral agents and contribute to vaccine escape mutants.

Conclusions:

  • A significant number of CHB patients develop drug resistance to LAM, compromising treatment efficacy.
  • The emergence of LAM-resistant strains necessitates the development and approval of more potent antiviral drugs with high genetic barriers.
  • A potent first-line treatment option with a high genetic barrier is crucial for improving long-term outcomes in pediatric CHB.

Keywords:
ChildrenChronic hepatitis BLamivudineLamivudine-resistant mutantsYMDD mutation

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