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免疫逃逸突变在美国一家三级肝脏中心的 HBsAg 和抗-HBs 共存患者中普遍存在。

Immune-Escape Mutations Are Prevalent among Patients with a Coexistence of HBsAg and Anti-HBs in a Tertiary Liver Center in the United States.

机构信息

Liver Center, Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

Howard University Hospital, Howard University College of Medicine, Washington, DC 20060, USA.

出版信息

Viruses. 2024 Apr 30;16(5):713. doi: 10.3390/v16050713.

DOI:10.3390/v16050713
PMID:38793596
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11125813/
Abstract

The concurrent seropositivity of HBsAg and anti-HBs has been described among patients with chronic hepatitis B (CHB), but its prevalence is variable. HBV S-gene mutations can affect the antigenicity of HBsAg. Patients with mutations in the 'α' determinant region of the S gene can develop severe HBV reactivation under immunosuppression. In this study at a tertiary liver center in the United States, we evaluated the frequency and virological characteristics of the HBsAg mutations among CHB patients with the presence of both HBsAg and anti-HBs. In this cohort, 45 (2.1%) of 2178 patients were identified to have a coexistence of HBsAg and anti-HBs, and 24 had available sera for the genome analysis of the Pre-S1, Pre-S2, and S regions. The frequency of mutations in the S gene was significantly higher among those older than 50 years (mean 8.5 vs. 5.4 mutations per subject, = 0.03). Twelve patients (50%) had mutations in the 'α' determinant region of the S gene. Mutations at amino acid position 126 were most common in eight subjects. Three had a mutation at position 133. Only one patient had a mutation at position 145-the classic vaccine-escape mutation. Despite the universal HBV vaccination program, the vaccine-escape mutant is rare in our cohort of predominantly Asian patients.

摘要

HBsAg 和抗-HBs 同时阳性已在慢性乙型肝炎(CHB)患者中描述过,但其发生率存在差异。HBV S 基因突变可影响 HBsAg 的抗原性。在 S 基因的“α”决定簇区域发生突变的患者在免疫抑制下可能会发生严重的 HBV 再激活。在美国的一家三级肝脏中心进行的这项研究中,我们评估了 HBsAg 和抗-HBs 同时存在的 CHB 患者中 HBsAg 突变的频率和病毒学特征。在该队列中,2178 例患者中有 45 例(2.1%)存在 HBsAg 和抗-HBs 共存,24 例有可用的血清进行 Pre-S1、Pre-S2 和 S 区的基因组分析。S 基因的突变频率在年龄大于 50 岁的患者中显著更高(平均每个患者 8.5 与 5.4 个突变, = 0.03)。12 例患者(50%)在 S 基因的“α”决定簇区域有突变。8 例患者的氨基酸位置 126 发生突变最为常见。3 例患者的位置 133 发生突变。只有 1 例患者的位置 145 发生突变,即经典的疫苗逃逸突变。尽管有普遍的乙型肝炎疫苗接种计划,但在我们的主要为亚洲患者的队列中,疫苗逃逸突变体很罕见。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aff/11125813/f1a904324179/viruses-16-00713-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aff/11125813/f1a904324179/viruses-16-00713-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aff/11125813/f1a904324179/viruses-16-00713-g001.jpg

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