Clin Mol Hepatol.  2015 Jun;21(2):131-140. 10.3350/cmh.2015.21.2.131.

Impact of prior lamivudine use on the antiviral efficacy and development of resistance to entecavir in chronic hepatitis B patients

• Hwang JA
• Kim KB
• Yang MJ
• Lim SG
• Hwang JC
• Cheong JY
• Cho SW
• Kim SS

• KMID: 2164363
• DOI: http://doi.org/10.3350/cmh.2015.21.2.131

Abstract

BACKGROUND/AIMS
To determine the efficacies of entecavir (ETV) in nucleos(t)ide analogue (NA)-naive chronic hepatitis B (CHB) patients and in those with prior lamivudine (LAM) use who did not develop resistance.
METHODS
We retrospectively enrolled 337 patients with CHB who were treated with ETV (0.5 mg daily) for at least 30 months. The study included 270 (80.1%) NA-naive patients and 67 (19.9%) LAM-use patients. Ten of the LAM-use patients were refractory to LAM therapy without developing resistance.
RESULTS
Genotypic resistance to ETV developed more frequently in the LAM-use group (13.1%) than in the NA-naive group (2.6%) at 60 months (P=0.009). In subgroup analysis, after excluding the 10 patients who were refractory to LAM therapy, the cumulative probability of ETV resistance did not differ significantly between the two groups (P=0.149). Prior LAM refractoriness and a higher hepatitis B virus DNA level at month 12 were independent predictive factors for the development of ETV resistance.
CONCLUSIONS
ETV resistance developed more frequently in LAM-use patients with CHB. However, prior LAM use without refractoriness did not affect the development of ETV resistance. The serum hepatitis B virus DNA level at month 12 was a major predictor for the development of ETV resistance.

Keyword

Chronic hepatitis B; Entecavir; Lamivudine; Resistance

MeSH Terms

Adolescent
Adult
Aged
Antiviral Agents/*therapeutic use
DNA, Viral/blood
*Drug Resistance, Viral/genetics
Female
Genotype
Guanine/*analogs & derivatives/therapeutic use
Hepatitis B virus/genetics
Hepatitis B, Chronic/*drug therapy/virology
Humans
Lamivudine/*therapeutic use
Male
Middle Aged
Remission Induction
Retrospective Studies
Young Adult
Antiviral Agents
DNA, Viral
Guanine
Lamivudine