[Predictors of lamivudine resistance in patients with chronic hepatitis B virus infection].
OBJECTIVE
Drug resistance is a major concern during nucleoside/ nucleotide 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 > 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/m(2)), 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.
Heo
Jeong
J
Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea.
Cho
Mong
M
Cho
Byung Mann
BM
Lee
Sun Mi
SM
Kim
Tae Oh
TO
Kim
Gwang Ha
GH
Kang
Dae Hwan
DH
Song
Geun Am
GA
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D005260:Female; D006513:Hepatitis B e Antigens / Q000032:analysis*; D006515:Hepatitis B virus / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies
D000998:Antiviral Agents; D015415:Biomarkers; D006513:Hepatitis B e Antigens; D019259:Lamivudine