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. CONCLUSION: This observation demonstrates the transient emergence of HBV variants in the course of therapy in a patient resistant to lamivudine therapy.
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. CONCLUSION: This observation demonstrates the transient emergence of HBV variants in the course of therapy in a patient resistant to lamivudine therapy.
Authors: L Stuyver; C Van Geyt; S De Gendt; G Van Reybroeck; F Zoulim; G Leroux-Roels; R Rossau Journal: J Clin Microbiol Date: 2000-02 Impact factor: 5.948
Authors: S Balakrishna Pai; A Mithat Bozdayi; Rekha B Pai; Tolunay Beker; Mustafa Sarioglu; Ahmet R Turkyilmaz; Jason Grier; Cihan Yurdaydin; Raymond F Schinazi Journal: Antimicrob Agents Chemother Date: 2005-07 Impact factor: 5.191
Authors: Richard K Gaillard; Jennifer Barnard; Vincent Lopez; Paula Hodges; Eric Bourne; Lance Johnson; Marchelle I Allen; Patrick Condreay; Wayne H Miller; Lynn D Condreay Journal: Antimicrob Agents Chemother Date: 2002-04 Impact factor: 5.191