Prevalence and clinical correlates of YMDD variants during lamivudine therapy for patients with chronic hepatitis B

Clin Infect Dis. 2003 Mar 15;36(6):687-96. doi: 10.1086/368083. Epub 2003 Mar 5.


YMDD variants of hepatitis B virus (HBV) emerge in some patients with chronic hepatitis B who receive lamivudine. YMDD variants were examined in 794 patients in 4 controlled studies of 1 year's duration. The long-term effects of YMDD variants were examined in a subset of patients treated up to 4 years. YMDD variants were detected by polymerase chain reaction (PCR) and restriction fragment-length polymorphism assays. After 1 year, YMDD variants were detected in 81 (24%) of 335 patients. In these patients, the median serum HBV DNA concentration at 1 year was <20% of the baseline level, and serum alanine transaminase (ALT) levels and liver histologic findings had significantly improved. In patients with YMDD variants who were treated for up to 4 years, median HBV DNA and ALT levels showed improvements. Sex, baseline body mass index, and HBV DNA level were associated with emergence of YMDD variants. Patients with YMDD variants losing clinical response with a significant increase in the HBV DNA and ALT levels may require additional therapy.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alanine Transaminase / blood
  • Antiviral Agents / adverse effects*
  • Antiviral Agents / therapeutic use
  • DNA, Viral / blood
  • Drug Resistance, Viral
  • Hepatitis B e Antigens / analysis
  • Hepatitis B e Antigens / immunology
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology*
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / drug therapy
  • Hepatitis B, Chronic / epidemiology*
  • Hepatitis B, Chronic / virology
  • Humans
  • Lamivudine / adverse effects*
  • Lamivudine / therapeutic use
  • Prevalence


  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B e Antigens
  • Lamivudine
  • Alanine Transaminase