Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University, Fatih, Istanbul 34093, Turkey.
Department of Internal Medicine, Istanbul Faculty of Medicine, Division of Gastroenterohepatology, Istanbul University, Istanbul, Turkey.
Virus Res. 2022 Sep;318:198855. doi: 10.1016/j.virusres.2022.198855. Epub 2022 Jul 4.
This study aimed to detect mutations in the HBV S gene and evaluate their relationship to occult hepatitis B virus (HBV) infection (OBI).
The study included 32 patients with negative serum HBsAg and HBV DNA who underwent liver biopsy due to different clinical indications defined as the OBI group and 32 patients who underwent liver biopsy due to chronic hepatitis B (CHB) as the comparison group. The HBV S gene region was amplified by Nested PCR, and Sanger sequencing was performed.
At least one amino acid (aa) mutation was detected in the major hydrophilic region (MHR) of the HBV S gene in 14/32 (43.75%) of the patients with OBI and 8/32 (25.0%) with CHB. The genotype of all patients with OBI and CHB was HBV/D. Although 9 (28.1%) of the cases with OBI had sub-genotype HBV/D3, none of the patients with CHB had sub-genotype HBV/D3. Unlike patients with CHB, L15*, D33N, Q51P, V63F, L91I, P108S, T115I, P120L, T125M, Q129H, T189I, L216F, P217L mutations were detected in the HBV S gene in OBI cases. Also, P127T aa polymorphism was frequently detected. Mutation frequency in the HBV S gene in the major hydrophilic region (MHR) was higher in patients with OBI with sub-genotypes HBV/D3 and D2 than those with HBV/D1 and those with serotype HBV/ayw3 compared to those with HBV/ayw2 (p < 0.05).
Sub-genotypic-specific mutation patterns were seen in the "a" determinant region and T helper cell epitopes of HBsAg, especially in the C-terminus domain; this may be associated with OBI.
本研究旨在检测乙型肝炎病毒（HBV）S 基因中的突变，并评估其与隐匿性乙型肝炎病毒（OBI）感染的关系。
研究纳入了 32 例因不同临床指征行肝活检且血清 HBsAg 和 HBV DNA 均阴性的患者，定义为 OBI 组，以及 32 例因慢性乙型肝炎（CHB）行肝活检的患者作为对照组。采用巢式 PCR 扩增 HBV S 基因区，并进行 Sanger 测序。
OBI 组 14/32（43.75%）和 CHB 组 8/32（25.0%）患者的 HBV S 基因主要亲水区（MHR）至少存在 1 个氨基酸（aa）突变。所有 OBI 和 CHB 患者的基因型均为 HBV/D。虽然 OBI 组有 9 例（28.1%）为亚基因型 HBV/D3，但 CHB 组无亚基因型 HBV/D3。与 CHB 患者不同，OBI 患者的 HBV S 基因中检测到 L15*、D33N、Q51P、V63F、L91I、P108S、T115I、P120L、T125M、Q129H、T189I、L216F、P217L 等突变，此外还经常检测到 P127T aa 多态性。亚基因型 HBV/D3 和 D2 的 OBI 患者 MHR 区 HBV S 基因的突变频率高于亚基因型 HBV/D1 和 HBV/ayw3 患者以及 HBV/ayw2 患者（p<0.05）。
HBV S 基因“a”决定簇区和 HBsAg 辅助性 T 细胞表位出现了亚基因型特异性的突变模式，特别是在 C 末端区，这可能与 OBI 有关。
