Detection and analysis of resistance mutations of hepatitis B virus.

Objective: To investigate the relationships of resistance mutations of hepatitis B virus (HBV) with replication and genotypes of HBV and to understand the common resistance mutations and mutation pattern.

Methods: The mutation patterns related to resistance to nucleoside drugs were analyzed, and the relationships of resistance mutations with HBV genotypes, Ct value, HBeAg, alanine aminotransferase (ALT), age and gender were evaluated.

Results: Genotype B was found in 52 patients (73.2%) and genotype C in 19 patients (26.8%). In addition, 32 patients (45.07%) had resistance mutations at different loci, of which single base mutation accounted for 56.25% (18/32) and multi-base mutation for 43.75% (14/32). Of single base mutation, L180M, M204I, M204V and V173L had higher prevalence, and the incidence of L180M was closely related to the genotype of HBV. L180M, M204I and M204V were associated with the resistance to lamivudine and telbivudine; L180M, M204I, M204V and V173L were associated with the resistance to entecavir; A181T, N236T and N/H238T were related to the resistance to adefovir. Of multi-base mutations, L180M combined M204V had a high prevalence and were frequently found in patients with resistance to lamivudine and telbivudine. There was cross-resistance between lamivudine and telbivudine, between lamivudine and entecavir, and between entecavir and telbivudine. The Ct value of HBV DNA, HBeAg, ALT, age and gender were comparable among patients with different resistance mutations and HBV genotypes.

Conclusion: Detection of mutations of multiloci resistance genes is helpful for timely identification of HBV resistance and the clinical anti-virus therapy.