Main mutations in the hepatitis B virus basic core promoter (A1762T/G1764A) before HBeAg loss are markers that identify patients who will require long-term treatment

Abstract

Background Some patients continue to have detectable HBV-DNA levels with liver disease progression after hepatitis B e antigen (HBeAg) loss. It is important to identify these patients, candidates for long-term treatment. Aims To evaluate hepatitis B virus (HBV) genotype and the main mutations in the basic core promoter (BCP, A1762T/G1764A) and precore (G1896A) sequences as markers of persistent HBV-DNA after HBeAg loss. Methods We analysed 60 serum samples from 20 Caucasian, HBeAg-positive, chronic hepatitis B patients, who lost HBeAg and were followed-up longitudinally. HBV genotype and precore and BCP mutations were determined before, at the time of, and after HBeAg loss. Results After HBeAg loss, eight (40%) patients continued to have undetectable HBV-DNA and 12 (60%) had persistent HBV-DNA (median level 4.7 log 10 copies/mL). The presence of BCP mutations prior to therapy was the only variable associated with persistently detectable viraemia (P = 0.017). Four patients with genotype A and no mutations in the BCP region experienced hepatitis B surface antigen (HBsAg) loss after a mean period of 35 months from baseline. Conclusions Main BCP mutations in HBeAg-positive patients are useful markers to identify patients who will not have sustained virological suppression after HBeAg loss and therapy discontinuation and could benefit from long-term treatment. © 2010 Blackwell Publishing Ltd.