HLA-DRB1*010101 等位基因与慢性乙型肝炎患者拉米夫定治疗的病毒学应答不佳密切相关。

HLA-DRB1*010101 allele is closely associated with poor virological response to lamivudine therapy in patients with chronic hepatitis B.

机构信息

Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

出版信息

Digestion. 2011;84 Suppl 1:35-42. doi: 10.1159/000333783. Epub 2011 Dec 2.

Abstract

BACKGROUND/AIMS: We intended to evaluate the association between specific human leukocyte antigen (HLA)-DRB1 gene polymorphism and antiviral response to lamivudine (LAM) therapy in chronic hepatitis B (CHB) patients.

METHODS

Six-digit HLA-DRB1 genotypes were determined using sequence-based typing in 334 CHB patients initially treated with LAM for at least 12 months. Antiviral response was evaluated every 3-6 months during LAM therapy.

RESULTS

Median age of the subjects was 43 years (range, 16-72). Median duration of LAM therapy was 69 months (range, 13-140). Median baseline serum hepatitis B virus (HBV DNA) level was 7.0 log(10) copies/ml (range, 5.5-9.1). At 12 months of LAM therapy, serum HBV DNA was undetectable by solution hybridization method in 308 (88%) patients. Among 25 HLA-DRB1 alleles identified, HLA-DRB1*090102, 080302, and 070101 were the most frequent alleles (>10%). HLA-DRB1010101 was identified in 5.4% (18/334). The frequency of the HLA-DRB1010101 allele was significantly lower in patients with virological response at 12 months of LAM therapy than in patients without it (4.2 vs. 19.2%, p = 0.025). The other HLA-DRB1 alleles were not associated with virological response. HBeAg loss/seroconversion and alanine aminotransferase normalization were not associated with HLA-DRB1 alleles.

CONCLUSION

The HLA-DRB1*010101 allele is closely associated with poor virological response to initial LAM therapy in CHB patients.

摘要

背景/目的：我们旨在评估特定人类白细胞抗原（HLA）-DRB1 基因多态性与慢性乙型肝炎（CHB）患者拉米夫定（LAM）治疗的抗病毒反应之间的关联。

方法

334 例初治 LAM 至少 12 个月的 CHB 患者，采用基于序列的分型方法确定 6 位 HLA-DRB1 基因型。在 LAM 治疗期间，每 3-6 个月评估一次抗病毒反应。

结果

受试者的中位年龄为 43 岁（范围 16-72 岁）。LAM 治疗的中位时间为 69 个月（范围 13-140 个月）。中位基线血清乙型肝炎病毒（HBV）DNA 水平为 7.0 log(10) 拷贝/ml（范围 5.5-9.1）。在 LAM 治疗 12 个月时，308 例（88%）患者的血清 HBV DNA 用杂交法检测不到。在鉴定的 25 个 HLA-DRB1 等位基因中，HLA-DRB1090102、080302 和070101 是最常见的等位基因（>10%）。HLA-DRB1010101 占 5.4%（18/334）。在 LAM 治疗 12 个月时有病毒学应答的患者中，HLA-DRB1*010101 等位基因的频率明显低于无病毒学应答的患者（4.2%比 19.2%，p=0.025）。其他 HLA-DRB1 等位基因与病毒学反应无关。HBeAg 丢失/血清转换和丙氨酸氨基转移酶正常化与 HLA-DRB1 等位基因无关。