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

David Tabernero (1, 2) , Mayra J Sánchez (3) , Maria Homs (1, 2) , Francisco Rodriguez-Frias (1, 2) , Rossend Jardi (1, 2) , Melanie Schaper (1, 2) , Rafael Esteban (1, 3) , Maria A Buti (1, 3)

1 CIBERehd - Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas
2 Biochemistry Unit
3 Liver Unit

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 analyzed 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, 8 (40%) patients continued to have undetectable HBV-DNA and 12 (60%) had persistent HBV-DNA (median level 4.7 log10 copies/mL). The presence of BCP mutations prior to therapy was the only variable associated with persistently detectable viremia (P=0.017). Four patients with genotype A and no mutations in the BCP region experienced 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 virologic suppression after HBeAg loss and therapy discontinuation, and could benefit from long-term treatment.

Mots clés: Medicine

David Tabernero, Mayra J Sánchez, Maria Homs, Francisco Rodriguez-Frias, Rossend Jardi, et al.. 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. Alimentary Pharmacology and Therapeutics, 2010, ⟨10.1111/j.1365-2036.2010.04319.x⟩. ⟨hal-00552557⟩