Background
/Aim: Drug resistance is a major concern during nucleos(t)ide analogues therapy in patients
with chronic hepatitis B virus (HBV) infections. The aim of this study was to measure the risk of lamivudine
resistance provided for each predictive factor in patients with chronic HBV infections. Methods: A total of 183
patients were analyzed among 315 patients with chronic HBV infections enrolled in a tertiary referral hospital
between January 2001 and December 2003 on this retrospective cohort study. AST/ALT, HBeAg/anti-HBe,
serum HBV DNA levels were tested for every 3 or 6 months. HBV DNA level was tested using Cobas
Amplicor HBV Monitor test™. Viral breakthrough was defined as HBV DNA ≥ 5 log10 copies/mL on two
consecutive visits in patients who, on treatment, achieved HBV DNA < 5 log10 copies/mL. The risk of viral
breakthrough was measured using Cox proportional hazards model for variables: age, sex, BMI (kg/m2),
baseline ALT, HBeAg positivity, baseline HBV DNA level, serum HBV DNA level at 6 month of lamivudine
therapy. Results: The cumulative rates of viral breakthrough were 9.6%, 39.0%, 55.8% at 12, 24, 36 months,
respectively. Serum HBV DNA level of 6 month of lamivudine therapy and presence of HBeAg were
independent predictors for viral breakthrough. The relative risk was 1.43 (95% C.I. 1.09-1.89, P=0.010) for
serum HBV DNA level at 6 months of lamivudine therapy and 1.77 (95% C.I. 1.06-2.95, P=0.029) for presence
of HBeAg. Conclusions: Serum HBV DNA level at 6 months of therapy and HBeAg positivity were predictors
of early lamivudine resistance in patients with chronic HBV infections. An alternate therapy should be
considered when serum viral load is high at 6 months of lamivudine therapy. (Korean J Hepatol 2007;13:157-
165)
