Severe acute exacerbation of liver disease may reduce or delay emergence of YMDD motif mutants in long-term lamivudine therapy for hepatitis B e antigen-positive chronic hepatitis B.

The pretherapy factors that could influence the emergence of resistant hepatitis B virus (HBV) tyrosine-methionine-aspartate-aspartate (YMDD) motif mutants against lamivudine are not fully known in prolonged lamivudine therapy for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B. We analyzed prospectively 116 consecutive lamivudine-naïve patients who received long-term lamivudine therapy (>1 year) by using multivariate regression analyses. The cumulative HBeAg loss rates were 29, 44, and 47% at 1, 2, and 3 years of treatment, respectively. Stepwise Cox's regression analyses indicated that pretherapy viral load was a significant factor associated with HBeAg loss (P = 0.0068). The cumulative emergence rates of YMDD mutants were 23% at 1 year, 45% at 2 year, and 47% at 3 year of treatment. Stepwise Cox's regression analyses indicated that patient age and presence or absence of severe acute exacerbation of liver disease were independent significant factors associated with emergence of YMDD mutants (P = 0.018 and 0.048, respectively). For the development of virological breakthrough, patient age, the presence or absence of severe acute exacerbation, and pretherapy viral load were independent significant factors (P = 0.028, 0.043, and 0.044, respectively). Severe acute exacerbation tended to reduce or delay development of biochemical breakthrough. The present study provides important information for the development of more effective and rational long-term lamivudine therapy for HBeAg-positive chronic hepatitis B patients infected exclusively with genotype

Tsubota A ，Arase Y ，Suzuki F ，Kobayashi M ，Matsuda M ，Sato J ，Suzuki Y ，Akuta N ，Sezaki H ，Hosaka T ，Someya T ，Kobayashi M ，Saitoh S ，Ikeda K ，Kumada H ... -  《JOURNAL OF MEDICAL VIROLOGY》

The clinical impact of early detection of the YMDD mutant on the outcomes of long-term lamivudine therapy in patients with chronic hepatitis B.

Paik YH ，Han KH ，Hong SP ，Lee HW ，Lee KS ，Kim SO ，Shin JE ，Ahn SH ，Chon CY ，Moon YM ... -  《ANTIVIRAL THERAPY》

Long-term follow-up of lamivudine treatment in patients with severe acute exacerbation of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B.

Wong VW ，Wong GL ，Tsang SW ，Hui AY ，Chim AM ，Yiu KK ，Chan HY ，Chan FK ，Sung JJ ，Chan HL ... -  《ANTIVIRAL THERAPY》

Changes in serum hepatitis B e antigen (HBeAg) levels associated with the emergence of YMDD mutants in HBeAg non-seroconverted patients during lamivudine therapy.

Yen YH ，Lu SN ，Chen CH ，Wang JH ，Wu CM ，Hung CH ，Tseng PL ，Hu TH ，Changchien CS ，Lee CM ... -  《LIVER INTERNATIONAL》

Clinical and virological effects of long-term (over 5 years) lamivudine therapy.

Ideally, long-term lamivudine therapy should not induce tyrosine-methionine-aspartate-aspartate (YMDD) mutants (reverse transcription [rt]; rt M204I/V) in patients with chronic hepatitis B. There is little or no information on the clinical features of patients who do not develop such mutants. We analyzed 368 patients who received lamivudine therapy for more than 6 months between 1995 and 2003. Among them, 98 patients were negative for YMDD mutants during 5-year lamivudine therapy. Multivariate analysis identified hepatitis B e antigen (HBeAg) negativity, lack of cirrhosis, and high gamma glutamyltranspeptidase (GGTP) level as independent factors associated with lack of emergence of YMDD mutants during 5-year treatment. In these 98 patients, 21 patients developed YMDD mutants in the 5-year posttreatment follow-up. Old age was identified as the only factor associated with the emergence of YMDD mutants during that period. For all patients, 53 showed no elevation of alanine aminotransferase (ALT) or viral load after emergence of YMDD mutants during 5 years. Short latency to emergence of YMDD mutants, mixed (tyrosine-isoleucine-aspartate-aspartate (YIDD) [rtM204I] + tyrosine-valine-aspartate-aspartate (YVDD) [rtM204V]) type, and low ALT level were identified as independent factors associated with elevation ALT or viral load. HBeAg negativity, lack of cirrhosis, and high GGTP level were associated with lack of emergence of YMDD mutants during 5-year period. Young age protected against emergence of YMDD mutants over the 5-year period. Moreover, after the emergence of YMDD mutants, short latency to the emergence of YMDD mutant, mixed type mutants, and low baseline ALT level were associated with elevation of ALT or viral load.

Hashimoto Y ，Suzuki F ，Hirakawa M ，Kawamura Y ，Yatsuji H ，Sezaki H ，Hosaka T ，Akuta N ，Kobayashi M ，Saito S ，Suzuki Y ，Kobayashi M ，Arase Y ，Ikeda K ，Kumada H ... -  《-》