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.
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.


OBJECTIVE
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.
Tabernero
D
D
Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas, Barcelona, Spain.
Sánchez
M J
MJ
Homs
M
M
Rodríguez-Frías
F
F
Jardí
R
R
Schaper
M
M
Esteban
R
R
Buti
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D006513:Hepatitis B e Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D013223:Statistics as Topic; D013997:Time Factors; D055815:Young Adult
D004279:DNA, Viral; D005819:Genetic Markers; D006513:Hepatitis B e Antigens