Entecavir is superior to lamivudine in reducing hepatitis B virus DNA in patients with chronic hepatitis B infection

Gastroenterology. 2002 Dec;123(6):1831-8. doi: 10.1053/gast.2002.37058.


Background & aims: Entecavir is a novel and selective nucleoside analogue with potent activity against hepatitis B virus (HBV).

Methods: In a 24-week, double-blind, randomized, multicenter, phase II clinical trial, the safety and efficacy of entecavir (0.01 mg/day, 0.1 mg/day, or 0.5 mg/day orally) were compared with lamivudine (100 mg/day orally). Patients (n = 169) chronically infected with HBV (hepatitis B e antigen [HBeAg]-positive and -negative) were evaluated for efficacy.

Results: Compared with lamivudine, entecavir reduced HBV DNA by an additional 0.97 log(10) at the 0.1-mg/day dose and an additional 1.28 log(10) at the 0.5-mg/day dose (P < 0.0001). A clear dose-response relationship was observed for entecavir with the higher doses showing significantly greater viral suppression. In patients treated with entecavir 0.5 mg/day, 83.7% had an HBV-DNA level below the lower limit of detection of the Quantiplex branched DNA (bDNA) assay (Bayer-Versant Diagnostics, formerly Chiron Diagnostics, Emeryville, CA), compared with 57.5% treated with 100 mg/day lamivudine (P = 0.008). In both treatment arms, very few patients achieved HBeAg loss and/or seroconversion by week 22. More patients treated with the 0.1-mg/day and 0.5-mg/day doses of entecavir had normalization of alanine transaminase (ALT) levels at week 22 compared with lamivudine (P = not significant). Entecavir was well tolerated; most adverse events were mild to moderate, transient, and comparable in all study arms.

Conclusions: This study showed that entecavir has potent antiviral activity against HBV at 0.1-mg/day and 0.5-mg/day doses, both of which were superior to lamivudine in chronically infected HBV patients.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alanine Transaminase / blood
  • DNA, Viral / metabolism*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Guanine / administration & dosage
  • Guanine / adverse effects
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use*
  • Hepatitis B e Antigens / analysis
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / genetics*
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / genetics
  • Hepatitis B, Chronic / pathology
  • Hepatitis B, Chronic / virology*
  • Humans
  • Lamivudine / administration & dosage
  • Lamivudine / adverse effects
  • Lamivudine / therapeutic use*
  • Male
  • Middle Aged
  • Reverse Transcriptase Inhibitors / administration & dosage
  • Reverse Transcriptase Inhibitors / adverse effects
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Treatment Outcome
  • Viral Load


  • DNA, Viral
  • Hepatitis B e Antigens
  • Reverse Transcriptase Inhibitors
  • Lamivudine
  • entecavir
  • Guanine
  • Alanine Transaminase