Hepatitis B virus DNA levels at week 4 of lamivudine treatment predict the 5-year ideal response

Hepatology. 2007 Dec;46(6):1695-703. doi: 10.1002/hep.21939.


The best time and hepatitis B virus (HBV) DNA level during an early lamivudine treatment period for predicting the long-term outcome are unknown. We aimed to determine the optimal time and HBV DNA level during an early treatment period for the prediction of the response after a 5-year lamivudine treatment. The HBV DNA levels at the baseline, at weeks 2, 4, 8, 12, 16, 24, and 32, and at yearly intervals until year 5 were measured in 74 hepatitis B e antigen (HBeAg)-positive chronic HBV patients receiving lamivudine treatment. Seventeen patients achieved an ideal response [HBV DNA level < 2000 copies/mL (400 IU/mL), HBeAg seroconversion, normal alanine aminotransferase levels, and absence of tyrosine-methionine-aspartate-aspartate (YMDD) mutations] at year 5. Receiver operating characteristic curves showed good predictions as early as week 4. The areas under the curve for weeks 4 and 16 were 0.89 and 0.94, respectively. Predictive indices revealed 4 and 3.6 log copies/mL (2000 and 800 IU/mL, respectively) to be the best cutoff HBV DNA levels for these 2 times, respectively. All patients with HBV DNA levels lower than these respective cutoff levels at the 2 times achieved an ideal response at year 5. Patients with HBV DNA levels above these cutoff values had 83.8% and 87.7% chances of not achieving an ideal response at year 5, respectively.

Conclusion: The measurement of the HBV DNA levels at week 4 of lamivudine treatment should be performed in all patients to predict the long-term outcome. The treatment can be continued for those with HBV DNA levels of less than 4 log copies/mL (2000 IU/mL). The addition of or switch to alternative antiviral agents should be considered for patients who fail to achieve this early target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antiviral Agents / therapeutic use*
  • DNA, Viral / blood
  • Female
  • Hepatitis B virus*
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Lamivudine / therapeutic use*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Treatment Outcome
  • Viral Load


  • Antiviral Agents
  • DNA, Viral
  • Lamivudine