Clinical characteristics of patients with chronic hepatitis B who developed genotypic resistance to entecavir: Real-life experience

Background/Aims: Clinical characteristics of patients with chronic hepatitis B (CHB) who developed genotypic resistance to entecavir (ETV) were compared to those without resistance. Methods: Two hundred fifty eight CHB patients who underwent ETV treatment in our institution from July 2007 to May 2013 were included. Results: Eight (3.1%) patients developed genotypic resistance to ETV during the follow-up period. The patterns of genotypic resistance to ETV were as follows: L180M + M204V + S202G (n=3); M204I + V173M (n=1); I169V + V173M (n=1); L180M + M204V + V173L (n=1); L180M + M204V + V173L + M250V (n=1); M204I + V214A + P237H (n=1). The cumulative occurrence rates of genotypic resistance to ETV were not significantly different between CHB patients with prior nucleos(t)tide analogues (NA) exposure (NA experienced, n=56) and NA naïve patients (n=202, P=0.823 by log rank comparison). Older age, higher baseline log ₁₀ hepatitis B virus-deoxynucleic acid (log10HBV-DNA), higher log ₁₀ HBV-DNA at 3, 6, 12 and 24 months after baseline, and complete virologic response (CVR, undetectable serum HBV-DNA by polymerase chain reaction 6 months after ETV treatment) were significant contributors to the development of genotypic resistance to ETV. Multivariate analyses showed higher log ₁₀ HBV-DNA 6 months after baseline and absence of CVR were independent and significant contributors to the development of ETV resistance. Conclusions: Clinical characteristics of patients who developed ETV resistance were higher log ₁₀ HBV-DNA 6 months after baseline and absence of CVR during the ETV treatment.