HBV infection may lead to acute liver disease, chronic active hepatitis, liver cirrhosis, and hepatocellular carcinoma. Over 350 million people worldwide are estimated to be infected chronically by HBV and are therefore at risk of liver failure, cirrhosis, or hepatocellular carcinoma. The principal treatment for chronic hepatitis B (CHB) involves the use of interferon alpha (IFN-a) or nucleoside analogs. In vitro analysis of clinical HBV isolates is currently difficult for lacking of HBV cellular culture model
A research article to be published on 14 June 2008, in the World Journal of Gastroenterology addresses this question. The research team led by Prof. Yin-Ping Lu from Union Hospital of Tongji Medical College reportd a useful strategy to select anti-HBV agents for drug-resistance patients. The full-length HBV genomic DNA from chronic hepatitis B patients were amplified by polymerase chain reaction (PCR). The amplified HBV DNA fragments were inserted into an universal HBV expression vector respectively. The recombinant plasmids containing 1.1 copies of HBV genome were transient transfected into Huh7 cells and antiviral susceptibility of lamivudine and adefovir were analyzed in vitro model system. Furthermore, the antiviral susceptibility of adefovir in vivo were observed subsequently.
Eight clinical HBV isolates form different individual with lamivudine-resistance were cloned into HBV expression vector, and recombinant plasmids were transcient transfected into Huh7 cells. The results indicated that HBV genome of clinical HBV isolates could effectively replicate and be expressed in Huh7 cells. Adefovir but not lamivudine inhibited HBV replication both in vitro and in vivo.
The novel method described in this article enables rapidly selecting of anti-HBV agents in clinic and will be useful in future studies of antiviral therapy for chronic hepatitis B.