Serum HBV RNA is a predictor of early emergence of the YMDD mutant in patients treated with lamivudine

• Published in: Hepatology (Baltimore, Md.) Vol. 45; no. 5; pp. 1179 - 1186
• Main Authors: Hatakeyama, Tsuyoshi, Noguchi, Chiemi, Hiraga, Nobuhiko, Mori, Nami, Tsuge, Masataka, Imamura, Michio, Takahashi, Shoichi, Kawakami, Yoshiiku, Fujimoto, Yoshifumi, Ochi, Hidenori, Abe, Hiromi, Maekawa, Toshiro, Kawakami, Hiroiku, Yatsuji, Hiromi, Aisaka, Yasuyuki, Kohno, Hiroshi, Aimitsu, Shiomi, Chayama, Kazuaki
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-05-2007; Wiley
• Subjects: Adult; Amino Acid Motifs - genetics; Amino Acid Substitution; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiseptics; Antiviral agents; Biological and medical sciences; Biomarkers - blood; DNA, Viral - blood; Drug Resistance, Viral - genetics; Female; Guanine - analogs & derivatives; Guanine - therapeutic use; Hepatitis B virus - genetics; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - genetics; Human viral diseases; Humans; Infectious diseases; Lamivudine - therapeutic use; Male; Medical sciences; Middle Aged; Molecular Probe Techniques; Pharmacology. Drug treatments; Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral - genetics; RNA-Directed DNA Polymerase - genetics; Time Factors; Viral diseases; Viral hepatitis; Antiretroviral agent; RNA-directed DNA polymerase; RNA; Entecavir; Orthohepadnavirus; Hepatic disease; Viral hepatitis B; Hepadnaviridae; Reverse transcriptase inhibitor; Emergence; Nucleoside analog; Antiviral; Serum; Hepatitis B virus; Pyrimidine nucleoside; Human; Tyrosine; Thiol; Enzyme; Transferases; Methionine; Enzyme inhibitor; Lamivudine; Sulfur containing aminoacid; Infection; Virus; Nucleotidyltransferases; Treatment; Dideoxynucleoside; Viral disease; Antiseptic; Digestive diseases
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1002/hep.21581

Lamivudine (LAM) is a nucleoside analogue widely used for the treatment of chronic hepatitis B virus (HBV) infection. Emergence of resistant strains with amino acid substitutions in the tyrosine‐methionine‐aspartate‐aspartate (YMDD) motif of reverse transcriptase is a serious problem in patients on LAM therapy. The amount of covalently closed circular DNA in the serum is reported to be higher in patients who develop YMDD mutants than in those without mutants. However, there is no useful serum marker that can predict early emergence of mutants during LAM therapy. Analysis of patients who were treated with entecavir (n = 7) and LAM (n = 36) showed some patients had high serum levels of HBV RNA. Median serum levels of HBV RNA were significantly higher in patients in whom the YMDD mutant had emerged within 1 year (n = 6, 1.688 log copies/ml) than in those in whom the YMDD mutant emerged more than 1 year after treatment (n = 12, 0.456 log copies/ml, P = 0.0125) or in whom the YMDD mutant never emerged (n = 18, 0.688 log copies/ml, P = 0.039). Our results suggest that HBV RNA is a valuable predictor of early occurrence of viral mutation during LAM therapy. (HEPATOLOGY 2007;45:1179–1186.)