Hiroshima Institute of Life Sciences, 7-21, Nishi Asahi-Machi, Minami-Ku, Hiroshima-Shi, Hiroshima, 734-0002, Japan.
Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
Curr Microbiol. 2024 Nov 5;81(12):446. doi: 10.1007/s00284-024-03963-8.
Chronic hepatitis B (CHB) infection is influenced by both virological and host factors. A total of 5,920 CHB patients were classified into four groups based on HBV seromarkers: three-generation families (CHB grandmother, mother, and child), two-generation families (CHB mother/child pairs), individuals recovered from HBV infection, and a control group. Serological markers, viral load, liver function tests (LFT), HBV mutations, HLA-DQ variations, cytokine polymorphisms, and liver stiffness measurements (LSM) were analyzed using FibroScan. Point mutations in genes such as core/pre-core (G1896A/G1899A), polymerase (H248N, H267Q, N263D), S (G145R, S143L), and X (C1500T, T1464C) were observed in 30% of three-generation pairs and 20% of two-generation pairs. The three-generation group exhibited the highest mean liver stiffness measurement (LSM) (4.94 ± 1.24 kPa), which is considered a predictor for the development of hepatocellular carcinoma (HCC). Subsequent HLA allele analysis identified HLA-DQB105:01 (OR = 0.27) as a risk factor for treatment resistance, while HLA-DQB105 (OR = 0.98), HLA-DQB103 (OR = 0.80), and HLA-DQB104:01 (OR = 0.70) were associated with HBV persistence in both three- and two-generation groups. Higher frequencies of specific polymorphisms, including G/G (TNF-α: 75%; IL-18: 74%), A/A (IL-10: 74.28%), and C/C (IL-1ß: 80%), were significantly linked to persistent infection. Analysis of viral sequences, HLA-DQB1 variations, cytokine polymorphisms, and genetic relationships within the phylogenetic tree revealed that 40% of CHB patients from three-generation families were infected by a shared source of transmission, as indicated by the presence of the same HBV genotype. This study underscores the complex interplay of host and viral factors that influence hepatitis B infection outcomes and suggests potential familial transmission pathways.
慢性乙型肝炎 (CHB) 感染受病毒学和宿主因素的影响。根据 HBV 血清标志物，将 5920 例 CHB 患者分为 4 组：三代家庭（CHB 祖母、母亲和孩子）、两代家庭（CHB 母亲/孩子对）、HBV 感染康复者和对照组。使用 FibroScan 分析血清学标志物、病毒载量、肝功能试验 (LFT)、HBV 突变、HLA-DQ 变异、细胞因子多态性和肝硬度测量 (LSM)。在 30%的三代对和 20%的两代对中观察到核心/前核心 (G1896A/G1899A)、聚合酶 (H248N、H267Q、N263D)、S (G145R、S143L) 和 X (C1500T、T1464C) 基因的点突变。三代组的平均肝硬度测量值 (LSM) 最高 (4.94 ± 1.24 kPa)，这被认为是肝细胞癌 (HCC) 发展的预测因子。随后的 HLA 等位基因分析确定 HLA-DQB105:01(OR=0.27) 是治疗抵抗的危险因素，而 HLA-DQB105(OR=0.98)、HLA-DQB103(OR=0.80) 和 HLA-DQB104:01(OR=0.70) 与三代和两代组的 HBV 持续存在相关。特定多态性的更高频率，包括 G/G (TNF-α:75%；IL-18:74%)、A/A (IL-10:74.28%) 和 C/C (IL-1β:80%)，与持续感染显著相关。病毒序列、HLA-DQB1 变异、细胞因子多态性和系统发育树中的遗传关系分析表明，40%的三代家庭 CHB 患者是由共同的传播源感染的，这表明存在相同的 HBV 基因型。这项研究强调了宿主和病毒因素的复杂相互作用，这些因素影响乙型肝炎感染的结果，并提示了潜在的家族传播途径。
