Clinical reactivation during lamivudine treatment correlates with mutations in the precore/core promoter and polymerase regions of hepatitis B virus in patients with anti-hepatitis B e-positive chronic hepatitis.
BACKGROUND
Drug-resistant mutants may emerge in patients with chronic hepatitis B receiving lamivudine therapy.


OBJECTIVE
To evaluate whether different viral mutational patterns may be associated with clinical reactivation during lamivudine treatment in patients with chronic B hepatitis.


METHODS
Eight anti-hepatitis B e-positive patients with (group A) and 14 patients without clinical exacerbation (five anti-hepatitis B e-positive, group B1; nine hepatitis B e antigen-positive, group B2) during lamivudine treatment were investigated.


RESULTS
'Polymerase region': M204V/I variants were found in all group A patients, but in none of group B1 (P=0.0007) and in four of nine of group B2 (44%; P=0.02) patients. The L180M substitution was detected in four of eight (50%) of group A and in none of groups B1 and B2. 'Core promoter': the double basic core promoter (A1762T/G1764A) variant was detected in seven of eight (87%) of group A and in one of five (20%; P=0.03) of group B1 and one of nine (11%; P=0.002) of group B2 patients. 'Precore': the G1896A stop codon mutation was present in seven of eight (87%) of group A and in zero of five (P=0.004) of group B1 and one of nine (11%; P=0.002) of group B2.


CONCLUSIONS
Different mutational patterns were observed in the lamivudine-treated patients with and without exacerbation. There was an association of the basic core promoter and stop codon mutations with lamivudine resistance in patients with disease exacerbation.
Marrone
A
A
Internal Medicine and Hepatology, Second University of Naples, Napoli, Italy. aldo.marrone@unina2.it
Zampino
R
R
Karayannis
P
P
Cirillo
G
G
Cesaro
G
G
Guerrera
B
B
Ricciotti
R
R
del Giudice
E Miraglia
EM
Utili
R
R
Adinolfi
L E
LE
Ruggiero
G
G
D000328:Adult; D000595:Amino Acid Sequence; D018388:Codon, Terminator / Q000235:genetics; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000097:blood* / Q000276:immunology; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D014775:Virus Activation / Q000235:genetics
D018388:Codon, Terminator; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine