Predictors of Lamivudine Resistance in Patients with Chronic Hepatitis B Virus Infection

Korean J Hepatol > Volume 13(2); 2007 > Article

The Korean Journal of Hepatology 2007;13(2): 157-165.

Predictors of Lamivudine Resistance in Patients with Chronic Hepatitis B Virus Infection

Jeong Heo , Mong Cho , Byung Mann Cho , Sun Mi Lee , Tae Oh Kim , Gwang Ha Kim , Dae Hwan Kang , Geun Am Song

Department of Internal Medicine, Preventive Medicine1, Pusan National University School of Medicine, Busan, Korea

ABSTRACT

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)

KeyWords: Hepatitis B, chronic; Lamivudine; Drug resistance, viral; Predictors