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在拉米夫定治疗期间,中国慢性乙型肝炎患者 YMDD 突变的发生与 HBV 基因型、HBV-DNA 水平和 HBeAg 状态的相关性。

Correlation of the occurrence of YMDD mutations with HBV genotypes, HBV-DNA levels, and HBeAg status in Chinese patients with chronic hepatitis B during lamivudine treatment.

机构信息

Department of Chinese Pharmacy, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.

出版信息

Hepatobiliary Pancreat Dis Int. 2012 Apr;11(2):172-6. doi: 10.1016/s1499-3872(12)60144-1.

Abstract

BACKGROUND

Continuous lamivudine therapy is associated with high rates of YMDD mutations, which are the main causes of drug resistance. The current study explores the association of the emergence of YMDD mutations with pretherapy HBV genotype, HBV-DNA levels, HBeAg status, and serum alanine aminotransferase (ALT) levels in Chinese patients receiving lamivudine therapy for chronic hepatitis B.

METHODS

A total of 319 chronic hepatitis B patients who received lamivudine therapy for more than a year were enrolled in this study. YMDD mutations, HBV genotype, HBV-DNA levels, HBeAg status, and ALT levels were determined prior to their lamivudine treatment and every three months for a year of this therapy.

RESULTS

Among the 319 patients, 137 (42.95%) were infected with genotype B and 182 (57.05%) with genotype C. Up to 94 patients (29.47%) developed YMDD mutations within one year of lamivudine therapy. Furthermore, 50 patients with HBV genotype B and 44 patients with genotype C developed YMDD mutations (36.50% vs 24.18%, P<0.05). Logistic regression analysis showed that pretherapy HBV genotype, HBV-DNA levels, and HBeAg status are independent factors for the emergence of YMDD mutations (HBV genotype: OR=2.159, 95% CI 1.291-3.609, P=0.003; HBV-DNA: OR=1.653, 95% CI 1.231-2.218, P=0.001; HBeAg: OR=2.021, 95% CI 1.201-3.399, P=0.008).

CONCLUSIONS

HBV genotype, HBV-DNA levels, and HBeAg status at baseline are the independent factors associated with the emergence of YMDD mutations among Chinese patients receiving lamivudine therapy for chronic hepatitis B. These findings are helpful to the development of therapeutic strategies for these patients.

摘要

背景

持续拉米夫定治疗与 YMDD 突变的高发生率相关,而 YMDD 突变是导致药物耐药的主要原因。本研究旨在探讨中国慢性乙型肝炎患者接受拉米夫定治疗时,YMDD 突变的出现与治疗前 HBV 基因型、HBV-DNA 水平、HBeAg 状态和血清丙氨酸氨基转移酶(ALT)水平的关系。

方法

共纳入 319 例接受拉米夫定治疗超过 1 年的慢性乙型肝炎患者。在拉米夫定治疗前及治疗后每 3 个月测定 YMDD 突变、HBV 基因型、HBV-DNA 水平、HBeAg 状态和 ALT 水平。

结果

319 例患者中,137 例(42.95%)感染基因型 B,182 例(57.05%)感染基因型 C。94 例(29.47%)患者在拉米夫定治疗 1 年内发生 YMDD 突变。此外,50 例基因型 B 患者和 44 例基因型 C 患者发生 YMDD 突变(36.50%比 24.18%,P<0.05)。Logistic 回归分析显示,治疗前 HBV 基因型、HBV-DNA 水平和 HBeAg 状态是 YMDD 突变发生的独立危险因素(HBV 基因型:OR=2.159,95%CI 1.291-3.609,P=0.003;HBV-DNA:OR=1.653,95%CI 1.231-2.218,P=0.001;HBeAg:OR=2.021,95%CI 1.201-3.399,P=0.008)。

结论

中国慢性乙型肝炎患者接受拉米夫定治疗时,治疗前 HBV 基因型、HBV-DNA 水平和 HBeAg 状态是 YMDD 突变发生的独立危险因素。这些发现有助于制定针对这些患者的治疗策略。

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