Abstract: Objective To elucidate the impact of hepatitis B virus rtN238H variant on adefovir resistance. Methods The rtN238H incidence and its relationship with adefovir（ADV）administration were analyzed in 1789 patients with chronic hepatitis B. The rtN238N variant from a representative case was cloned and its wild-type counterpart was acquired by reverse site-directed mutagenesis. pTriEx-HBV1. 1 vetors harboring N238H variant or wild-type strain were respectively constructed and transfected into HepG2 cells. The cells were treated with serial concentration of ADV. After digesting uncoated DNA with DNase，HBV DNA in viral particles in culture supernatant was released and quantitated by real-time PCR. Results One hundred and eighty one（10.1%）patients were identified as having rtN238H，out of them，151（83.4%）were genotype B，and 30（16.6%）were genotype C；130 ADV-treated patients（71.8.%）had higher incidence of rtN238H variant than 51 ADV-untreated patients（28.2%）；However，compared to wild-type strain，rtN238H had similar sensitivity to ADV and viral replication competence in vitro. Conclusion The rtN238H is a naturally-developed polymorphism without direct impact on ADV sensitivity and viral replication.

Key words: Hepatitis B, Hepatitis B virus, Variant, Drug resistance, Adefovir