Liu Hongcan, Wan Zemin, She Lanhui, Zhu Yajuan, Cai Zhiliang, Wu Bin, Zhuang Qizhen, Ke Peifeng, Wu Xinzhong, Li Zhuo, Huang Xianzhang
Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Department of Infectious Diseases, Guangzhou Women and Children's Medical Center, Guangzhou, China.
Front Pharmacol. 2021 Apr 15;12:648170. doi: 10.3389/fphar.2021.648170. eCollection 2021.
: 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. : 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. : 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. : 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.
在慢性乙型肝炎（CHB）患者接受拉米夫定（LAM）治疗后，逆转录酶中酪氨酸-甲硫氨酸-天冬氨酸-天冬氨酸（YMDD）基序的出现是一个严重问题。然而，CHB炎症药理反应与YMDD突变模式之间的关系尚未得到充分阐明。本研究旨在探讨CHB患者的炎症药理反应及不同的YMDD突变模式。
我们通过生化、血清学和病毒学检测，对83例CHB患者的炎症药理反应和YMDD突变模式进行了研究，其中包括25例YMDD突变患者、25例检测中患者和33例无YMDD突变的对照患者。
YMDD突变模式的发生率各不相同。在25例YMDD突变患者中，YIDD是主要突变类型（72%），其次是YVDD（16%）和混合的YIDD + YVDD（12%）。YMDD突变的时间进程也有所不同。52.4%的患者在LAM治疗后不到12个月就发生了突变。YMDD突变患者的血清乙型肝炎病毒（HBV）DNA水平显著高于对照组和阴性组。YMDD突变患者的血清HbsAg和HbeAg也高于对照组和阴性组，尽管血清HbeAb未发现显著差异。突变组的ALT和AST水平也显著更高。
阐明CHB病理过程中的炎症药理反应和YMDD突变模式可能对YMDD突变患者的未来治疗具有指导意义。这可能会影响拉米夫定耐药HBV治疗策略的选择。
