Association between clinical features and YMDD mutations in patients with chronic hepatitis B following lamivudine therapy

Ma,Ying; Yuan,Yujun; Ma,Xianglin; Tang,Boru; Hu,Ximei; Feng,Juan; Tian,Li; Ji,Yaohua; Dou,Xiaoguang

doi:10.3892/etm.2016.3365

Association between clinical features and YMDD mutations in patients with chronic hepatitis B following lamivudine therapy

Authors:
- Ying Ma
- Yujun Yuan
- Xianglin Ma
- Boru Tang
- Ximei Hu
- Juan Feng
- Li Tian
- Yaohua Ji
- Xiaoguang Dou
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Affiliations: Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110817, P.R. China, Department of General Surgery, The Third People's Hospital of Wafangdian, Wafangdian, Liaoning 116300, P.R. China, Department of Geriatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110817, P.R. China, Department of Virus, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110817, P.R. China, Department of Infectious Disease, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110817, P.R. China
Published online on: May 19, 2016 https://doi.org/10.3892/etm.2016.3365
Pages: 847-853

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Abstract

The aim of the present study was to investigate the correlation between feature and genotype with regard to the tyrosine-methionine-aspartate-aspartate (YMDD) mutation in chronic hepatitis B patients after lamivudine (LAM) therapy. A total of 30 patients with chronic hepatitis B were recruited, who underwent one year of LAM therapy. The patients' alanine aminotransferase (ALT) level and hepatitis B envelope antigen (HBeAg) seroconversion were evaluated, hepatitis B virus (HBV) DNA was genotyped using a new genotyping method and YMDD mutations were analyzed prior to treatment and at 6 and 12 months after LAM treatment. Furthermore, the secondary protein structure of the HBV DNA polymerase gene (P gene) was analyzed. Following treatment, the results suggested that LAM therapy improved ALT normalization. There was no correlation between clinical effects and ALT level before treatment. After 12 months treatment, the rate of HBeAg loss increased and the rate of HBeAg seroconversion decreased linearly with the rise of baseline ALT level. While ALT normalization and HBeAg seroconversion were highest in patients with HBV genotype B, HBeAg loss and HBVDNA loss were highest in those with genotype C. The effect was predominant in genotype D. No YMDD mutations were identified prior to 6 months of LAM therapy. The rate of YMDD mutations after 12 months LAM therapy was 12.12%. Two patients with rtM204V + rtL180M belonged to genotype C and another patient with rtL180M alone belonged to genotype D. The turn of secondary protein structure of P gene changed to β sheet when a rtM204V mutation occurred, and no change of secondary protein structure was associated with the rtL180M mutation. Thus, the present results indicate that one year of LAM therapy is able to improve ALT normalization. Long‑term LAM therapy may induce YMDD mutation and drug resistance.

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