Abstract: Objectiv To understand current situation of natural resistance of hepatitis B virus （HBV） to lamivudine （LMV） and/or adefovir（ADV）and its association with the virus genotypes. Methods Five hundred and three cases of HBV infection without antiviral treatments were analyzed. The HBV genotypes and viral resistance gene mutations were examined by PCR-reverse dot hybridization gene chips. Results Sixty four of 503 patients （12.72%） with HBV infection were found to carry natural LMV resistance,with the frequency of 73.44%,significantly higher than that of 23.44% in ADV and that of 3.13% in combination of both LMV and ADV （P<0.01~0.05）. Genotype B was seen in 68.59% of CHB patients,which was markedly higher than type C （23.06%）,type D （2.59%） or type B+C （5.77%）（ P<0.05~0.01）. Type B dominates in gene mutations of natural resistance to LMV and ADV,among them rtM204V mutation was most frequently noted in 36.17% of LMV natural resistance （P<0.01~0.05） whereas rt236T mutation was detected in 46.67% of ADV natural resistance （P<0.01~0.05）. Two patients with LMV and ADV resistance showed type B,carrying rtM204V+rtN236T mutations.Conclusion sPatients with chronic hepatitis B in Shenzhen have a high frequency of natural resistance to LMV and/or ADV. Gene mutation mainly occurs in genotype B,with the sites of rtM204V and rtN236T. Detection of natural drug resistance combined with genotyping before treatment is of clinical significance in enhancing the therapeutic effect of CHB.

Key words: Hepatitis B virus, Natural resistance, Genotyping