III Division of Infectious Diseases, ASST Fatebenefratelli Sacco, Milano, Italy; Department of Biomedical and Clinical Sciences "Luigi Sacco", Università degli Studi di, Milano, Italy.
III Division of Infectious Diseases, ASST Fatebenefratelli Sacco, Milano, Italy; Department of Biomedical and Clinical Sciences "Luigi Sacco", Università degli Studi di, Milano, Italy.
Eur J Intern Med. 2020 May;75:50-54. doi: 10.1016/j.ejim.2020.01.006. Epub 2020 Jan 21.
chronic viral infections by both HCV and HIV may lead to polyclonal activation of B cells resulting in hypergammaglobulinemia. This study retrospectively analyzed the effect of HCV eradication with interferon-free direct-acting antiviral agents (DAAs) on the gamma globulin levels in HCV-infected patients with or without HIV coinfection to identify factors potentially associated with gamma globulins decrease.
The charts of patients treated with DAAs for HCV chronic infection between January 2015-June 2019 were retrospectively reviewed. Gamma globulin levels before treatment and 12 weeks after the end of anti-HCV therapy were evaluated along with liver tests, liver fibrosis stage by elastography, SVR achievement, HIV-coinfection. Multivariate analyses were carried out to assess the factors and the potential confounders related to the changes in gamma globulin levels.
A significant decrease of gamma globulin concentration was found in both cirrhotic and non-cirrhotic HCV-infected patients after treatment (from mean ± SD of 1.5 ± 0.44 g/dL to 1.31 ± 0.37 g/dL; p = 0.0001). Adjusted linear regression analyses of serum gamma globulin changes from baseline to SVR12 showed a positive significant association with pre-treatment gamma-globulin levels (β-coefficient -0.23; p = 0.0001), Metavir fibrosis score (β-coefficient -0.74; p = 0.008), ALT values and baseline HCV-RNA levels > 800,000. No difference was found between HIV-infected and HIV-uninfected patients.
Our study confirms previous preliminary observation of the decrease of serum gamma globulins after HCV eradication either achieved with interferon-based therapy or with DAAs, suggesting a leading role of the virus on the activation of B cell compartment and gamma globulins production.
HCV 和 HIV 等慢性病毒感染可导致 B 细胞多克隆激活，从而导致高球蛋白血症。本研究回顾性分析了无干扰素直接作用抗病毒药物（DAA）治疗 HCV 感染患者的 HCV 清除对 HCV 感染患者（有无 HIV 合并感染）球蛋白水平的影响，以确定与球蛋白下降相关的潜在因素。
回顾性分析了 2015 年 1 月至 2019 年 6 月期间接受 DAA 治疗的 HCV 慢性感染患者的病历。评估了治疗前和抗 HCV 治疗结束后 12 周的球蛋白水平，以及肝功能检查、弹性成像检测的肝纤维化分期、SVR 获得情况、HIV 合并感染情况。进行了多变量分析，以评估与球蛋白水平变化相关的因素和潜在的混杂因素。
治疗后，肝硬化和非肝硬化 HCV 感染患者的球蛋白浓度均显著下降（从平均±SD 的 1.5±0.44g/dL 降至 1.31±0.37g/dL；p=0.0001）。从基线到 SVR12 的血清球蛋白变化的调整线性回归分析显示，与治疗前球蛋白水平呈正显著相关（β系数-0.23；p=0.0001）、Metavir 纤维化评分（β系数-0.74；p=0.008）、ALT 值和基线 HCV-RNA 水平>800,000。HIV 感染和未感染患者之间无差异。
本研究证实了之前的初步观察结果，即 HCV 清除后（无论是采用干扰素治疗还是 DAA 治疗），血清球蛋白水平下降，提示病毒在 B 细胞区室的激活和球蛋白产生中起主导作用。
