Abstract

Background/Aims: Emergence of tyrosine-methionine-aspartate-aspartate (YMDD) motif in reverse transcriptase is a serious problem in chronic hepatitis B(CHB) patients after Lamivudine (LAM) therapy. However, the relationship between inflammation pharmacological reaction and YMDD mutational patterns of CHB has not been well-characterized. The aim of this study was to investigate the inflammation pharmacological reaction and different YMDD mutants patterns of CHB patients. Methods: We investigated the inflammation pharmacological reaction and YMDD mutational patterns through biochemical, serological and virological detection among 83 CHB patients, including 25 YMDD mutants, 25 under detection, and 33 control patients without YMDD mutants. Results: Prevalence of YMDD mutation patterns is different. Among 25 YMDD mutants patients, YIDD was the dominant mutation (72%), followed YVDD (16%) and the hybrid YIDD + YVDD (12%). The time course during the YMDD mutations was also different. 52.4% patients developed the mutation less than 12 months after the LAM therapy. Serum hepatitis B virus (HBV) DNA level in patients with YMDD mutants were significantly higher than that in control and negative groups. Serum HbsAg and HbeAg in patients with YMDD mutants were also higher than those in control and negative groups, despite no significant difference was found forserum HbeAb. ALT and AST levels were also significantly higher in mutants group. Conclusions: Illuminating inflammation pharmacological reaction and YMDD mutational patterns of CHB during pathological process may have implications for future therapy in YMDD mutation patients. This may have impact on the choice of treatment strategies for lamivudine-resistant HBV.

Highlights

  • Hepatitis B virus (HBV) infection has long been a serious public health problem all over the world (European Association for the Study of the Liver, 2017)

  • We investigated the inflammation pharmacological reaction and YMDD mutational patterns through biochemical, serological and virological detection among 83 chronic hepatitis B (CHB) patients, including 25 YMDD mutants, 25 under detection, and 33 control patients without YMDD mutants

  • HBV infection have a high risk of causing serious liver diseases, including liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC) (Samal et al, 2012)

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Summary

Introduction

Hepatitis B virus (HBV) infection has long been a serious public health problem all over the world (European Association for the Study of the Liver, 2017). Antiretroviral treatment is the main clinical treatment of HBV (European Association for the Study of the Liver, 2017). Lamivudine (LAM), the first nucleoside analogue approved for treatment of CHB (Lai et al, 1998), has been widely used in clinic because of its high effectiveness (Chen et al, 2014). The cause of the resistance was the mutation of the amino acid substitutions in the highly conserved tyr-met-asp-asp (YMDD) motif (Ling et al, 1996). YMDD mutation has serious interference and can lead to failure during LAM treatment in CHB (Zoulim and Locarnini, 2012)

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