Transient emergence of hepatitis B variants in a patient with chronic hepatitis B resistant to lamivudine.
BACKGROUND
Lamivudine is a cytosine nucleoside analogue that inhibits hepatitis B virus replication. Resistance to lamivudine monotherapy has been reported in patients who received lamivudine to prevent recurrent hepatitis B virus infection after liver transplantation. No cases of resistance have been described in patients who did not clear HBV DNA during lamivudine therapy.


METHODS
We report the case of an adult patient with chronic HBeAg-positive hepatitis B who had a hepatitis flare during lamivudine therapy. The patient did not respond to lamivudine and, at 4 months of treatment, developed a significant serum alanine aminotransferase elevation. Alanine aminotransferase levels remained elevated for 4 months and returned to baseline spontaneously. Lamivudine therapy was administered for 1 year (52 weeks) and after withdrawal, alanine aminotransferase levels remained elevated.


RESULTS
Sequencing studies of HBV DNA at week 52 showed the emergence of a lamivudine-resistant variant associated with two point mutations in the hepatitis B virus polymerase gene: one mutation led to amino acid substitution of methionine to valine at residue 552, in the highly conserved tyrosine-methionineaspartate-aspartate motif, part of the active site of the polymerase; the second mutation consisted of a substitution of leucine to methionine at residue 528. At week 54 of follow-up, both mutations were undetectable.


CONCLUSIONS
This observation demonstrates the transient emergence of HBV variants in the course of therapy in a patient resistant to lamivudine therapy.
Buti
M
M
Liver Unit, Hospital General Universitario Valle Hebron, Barcelona, Spain.
Jardi
R
R
Cotrina
M
M
Rodriguez-Frias
F
F
Esteban
R
R
Guardia
J
J
D000328:Adult; D000595:Amino Acid Sequence; D017124:Conserved Sequence; D004279:DNA, Viral / Q000097:blood; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D014644:Genetic Variation / Q000502:physiology*; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000503:physiopathology* / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D017354:Point Mutation / Q000235:genetics; D013997:Time Factors
D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D019259:Lamivudine; D004259:DNA-Directed DNA Polymerase