Korean J Hepatol.  2007 Jun;13(2):157-165.

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

• Heo J
• Cho M
• Cho BM
• Lee SM
• Kim TO
• Kim GH
• Kang DH
• Song GA

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(TM). Viral breakthrough was defined as HBV DNA > or = 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.

Keyword

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

MeSH Terms

Adult
Aged
Antiviral Agents/*therapeutic use
Biological Markers/analysis
Cohort Studies
Drug Resistance, Viral
Female
Hepatitis B e Antigens/*analysis
Hepatitis B virus/isolation & purification
Hepatitis B, Chronic/*drug therapy
Humans
Lamivudine/*therapeutic use
Male
Middle Aged
Prognosis
Retrospective Studies