Lamivudine treatment failure risks in chronic hepatitis B patients with low viral load

Digestion. 2013;88(4):266-71. doi: 10.1159/000356312.


Aim: To analyze the risk factors of lamivudine treatment failure (LTF) for the long-term use in patients with low viral load (LVL).

Material and methods: In this multicenter study, 548 antiviral naïve noncirrhotic adult patients with LVL (for HBeAg+ patients HBV DNA <10 9 copies/ml and for HBeAg–patients HBV DNA <10 7 copies/ml) were enrolled. As a control group, 46 lamivudine-initiated patients with high viral load (HVL) were included. Primary outcome was switching to or adding on another antiviral drug as a consequence of primary nonresponse, partial response, viral breakthrough or adverse events. Secondary outcomes included LTF rates at 1, 2, 3, 4 and 5 years and LTF-related viral and host factors.

Results: Among 594 patients, 294 had to change lamivudine at the follow-up. Primary nonresponse, partial response, viral breakthrough or adverse events frequencies were 6.8, 1.6, 64.5 and 0.1%, respectively. Five-year LTF rates were 61.3 and 84.2% in patients with LVL and HVL, respectively. Among patients with LVL, patients with <100,000 copies/ml and ≥ 100,000 copies/ ml had 54.8 and 67.3% LTF rates at the end of the 5th year, respectively. Logistic regression analysis of risk factors showed HBeAg+, hepatic activity index, HBV DNA, virological response at 6 months and duration of follow-up were independent predictors for LTF (p values were 0.001, 0.008, 0.003, 0.020 and 0.003, respectively).

Conclusion: Similar to patients with HVL, first-line lamivudine therapy is not efficient for long-term use in patients with LVL. LTF risk is so high even in the absence of worse predictive factors.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Antibodies, Viral / blood
  • Antiviral Agents / therapeutic use*
  • DNA, Viral / blood*
  • Drug Resistance, Viral
  • Female
  • Follow-Up Studies
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B e Antigens / immunology
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Lamivudine / therapeutic use*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Severity of Illness Index
  • Time Factors
  • Treatment Failure
  • Viral Load*


  • Antibodies, Viral
  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Lamivudine