Serum HBV RNA Is a Predictor of Early Emergence of Lamivudine Resistance

Epivir Pill

Hepatitis B virus (HBV) mutates rapidly and quickly develops resistance to targeted antiviral therapies such as lamivudine (Epivir-HBV), a widely used nucleoside analog. Emergence of resistant viral strains with amino acid substitutions in the tyrosine-methionine-aspartate-aspartate (YMDD) motif of HBV reverse transcriptase is a serious barrier to long-term effective therapy.

In the May 2007 issue of Hepatology, Japanese researchers reported on a study of HBV DNA levels and the emergence of YMDD mutations in 42 patients.

As background, the authors noted that the amount of covalently closed circular (ccc) DNA in the serum has been reported to be higher in patients who develop YMDD mutants than in those without such substitutions. However, so far there has been no useful serum marker that can predict early emergence of mutations during lamivudine therapy.

Results

• An analysis of 7 subjects treated with entecavir (Baraclude) and 36 treated with lamivudine showed that some patients had high serum levels of HBV RNA.

• Median serum levels of HBV RNA were significantly higher in the 6 patients in whom YMDD mutations emerged within 1 year (1.688 log copies/mL), compared with the 12 subjects in whom the mutant variants emerged more than 1 year after starting therapy (0.456 log copies/mL) (P = 0.0125).

• Among the 18 patients in whom YMDD mutants never emerged, the median HBV viral load was lower still (0.688 log copies/mL) (P = 0.039).

Conclusion

In conclusion, the authors wrote, "Our results suggest that HBV RNA is a valuable predictor of early occurrence of viral mutation during lamivudine therapy."

Department of Medicine and Molecular Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, and Department of Hepatology, Hiroshima Red Cross Hospital, Hiroshima-shi, Japan.

06/22/07

Reference
T Hatakeyama, C Noguchi, N Hiraga, and others. Serum HBV RNA is a predictor of early emergence of the YMDD mutant in patients treated with lamivudine. Hepatology 45(5): 1179-1186. May 2007.