Changes in different regions of hepatitis B virus gene in hepatitis B 'e' antigen-negative patients with chronic hepatitis B: the effect of long-term lamivudine therapy.
BACKGROUND
Lamivudine therapy for chronic hepatitis B has been associated with changes in different regions of the hepatitis B virus nucleotide sequence.


OBJECTIVE
To study changes in the sequences of polymerase and precore/core promoter regions of hepatitis B virus, before and during 5 years of therapy with lamivudine.


METHODS
Eighty consecutive samples were taken from 10 chronic hepatitis B 'e' antigen-negative patients.


RESULTS
Nine patients carried hepatitis B virus precore mutations during the study. Before therapy, wild type was replaced by A1896 in two (20%) cases. During treatment, A1896 reverted transitory to wild type in five cases (50%) and in one case wild type was replaced by A1896. The continuous detection of precore mutations during therapy was associated with a lower response rate. YMDD mutations were observed in nine cases and both, L180M and M204V/I mutations were simultaneously detected in six cases. About 75% of the patients with M204V mutations were responders and none with M204I or mixed pattern sustained response.


CONCLUSIONS
Hepatitis B 'e' antigen-negative patients exhibit changes in the precore regions both spontaneously and under lamivudine therapy, the transitory reversion to wild type being most frequently witnessed. Patients carrying M204V mutations are more likely to respond to therapy. If, in further studies, these results are confirmed some patients with YMDD mutations could benefit from prolonging the duration of lamivudine therapy.
Buti
M
M
Liver Unit, Servicio de Hepatologia, Hospital General Universitario Valle de Hebron, Barcelona, Spain. mbuti@vheborn.ne
Jardi
R
R
Rodriguez-Frias
F
F
Valdes
A
A
Schaper
M
M
Esteban
R
R
Guardia
J
J
D000328:Adult; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006513:Hepatitis B e Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*
D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine