Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.
Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, 100015, China.
Arch Virol. 2021 Jul;166(7):1853-1858. doi: 10.1007/s00705-021-05062-6. Epub 2021 Apr 19.
To investigate the association between immune-cell-related cytokines and the development of chronic hepatitis B (CHB), patients with chronic hepatitis B virus (HBV) infection in the immunotolerant (IT) phase (n = 30) or hepatitis B envelope antigen (HBeAg)-positive CHB (n = 250) were enrolled in this study. Serological indicators and plasma cytokine levels were measured at the time of enrollment. The results showed that there were significant differences in the median age of the patients (27 vs. 31 years), alanine aminotransferase levels (ALT, 29.85 vs. 234.70 U/L), alanine aminotransferase levels (AST, 23.40 vs. 114.90 U/L), HBsAg levels (4.79 vs. 3.88 log IU/ml), HBeAg levels (1606.36 vs. 862.47 S/CO), and the HBV DNA load (8.17 vs. 6.71 log IU/ml) between the IT and CHB groups (all P < 0.01). The median values of Fms-like tyrosine kinase 3 ligand (FLT3-L), interferon-gamma (IFN-γ), interleukin- 17A (IL-17A), and transforming growth factor beta (TGF-β1) were significantly higher in the IT group than in the CHB group (FLT3-L, 41.62 vs. 27.47 pg/ml; IFN-γ, 42.48 vs. 33.18 pg/ml; IL-17A, 15.66 vs. 8.90 pg/ml; TGF-β1, 4921.50 vs. 2234 pg/ml; all P < 0.01). The median IFN-α2, TGF-β3 and IL-10 levels in the IT group were significantly lower than those in the CHB group (IFN-α2, 15.24 vs. 35.78 pg/ml, P = 0.000; TGF-β3, 131.69 vs. 162.61 pg/ml, P = 0.025; IL-10, 5.02 vs. 7.9 pg/ml, P = 0.012). Multivariate logistic regression analysis indicated that TGF-β 1 (OR = 0.999, 95% CI 0.999-1.000, P < 0.001) and TGF-β2 levels (OR = 1.008, 95%CI 1.004-1.012, P < 0.001) were modestly but significantly associated with the incidence of CHB. The results suggest that TGF-β level might be an independent factor related to the occurrence of CHB.
为了研究免疫细胞相关细胞因子与慢性乙型肝炎(CHB)发展之间的关系,本研究纳入了免疫耐受(IT)期慢性乙型肝炎病毒(HBV)感染患者(n=30)或 HBeAg 阳性 CHB 患者(n=250)。在入组时测量了血清学指标和血浆细胞因子水平。结果显示,IT 组和 CHB 组患者的中位年龄(27 岁与 31 岁)、丙氨酸氨基转移酶(ALT,29.85 与 234.70 U/L)、天门冬氨酸氨基转移酶(AST,23.40 与 114.90 U/L)、HBsAg 水平(4.79 与 3.88 log IU/ml)、HBeAg 水平(1606.36 与 862.47 S/CO)和 HBV DNA 载量(8.17 与 6.71 log IU/ml)均存在显著差异(均 P<0.01)。IT 组的 Fms 样酪氨酸激酶 3 配体(FLT3-L)、干扰素-γ(IFN-γ)、白细胞介素-17A(IL-17A)和转化生长因子-β1(TGF-β1)的中位数均显著高于 CHB 组(FLT3-L,41.62 与 27.47 pg/ml;IFN-γ,42.48 与 33.18 pg/ml;IL-17A,15.66 与 8.90 pg/ml;TGF-β1,4921.50 与 2234 pg/ml;均 P<0.01)。IT 组的 IFN-α2、TGF-β3 和 IL-10 水平中位数显著低于 CHB 组(IFN-α2,15.24 与 35.78 pg/ml,P=0.000;TGF-β3,131.69 与 162.61 pg/ml,P=0.025;IL-10,5.02 与 7.9 pg/ml,P=0.012)。多变量逻辑回归分析表明,TGF-β1(OR=0.999,95%CI 0.999-1.000,P<0.001)和 TGF-β2 水平(OR=1.008,95%CI 1.004-1.012,P<0.001)与 CHB 的发生呈适度但显著相关。结果表明,TGF-β 水平可能是 CHB 发生的一个独立相关因素。