Marinos G, Naoumov N V, Rossol S, Torre F, Wong P Y, Gallati H, Portmann B, Williams R
Institute of Liver Studies, King's College School of Medicine and Dentistry, London, England.
Gastroenterology. 1995 May;108(5):1453-63. doi: 10.1016/0016-5085(95)90694-0.
BACKGROUND/AIMS: Patients with chronic hepatitis B infection have elevated plasma tumor necrosis factor (TNF) alpha levels. Two TNF-alpha receptors have been identified, each responsible for distinct TNF-alpha activities. The aim of this study was to evaluate the biological function of the elevated TNF-alpha in chronic hepatitis B virus infection by examining the two TNF signaling pathways in the evolution of hepatitis B-related liver injury.
The hepatic expression of the two TNF receptors and the corresponding serum levels of the soluble forms of both TNF receptors were determined and correlated with hepatic inflammation and virus replication in 98 chronic hepatitis B surface antigen carriers. Forty hepatitis B e antigen-positive patients were also studied prospectively, while on interferon alfa treatment, to examine the TNF receptor response during viral clearance.
In chronic hepatitis B virus infection, the hepatic expression and serum levels of TNF receptors, in particular 75-kilodalton TNF receptor subtype (TNF-R p75), are significantly enhanced in association with hepatic inflammation and hepatocytolysis but not with hepatitis B virus replication. During interferon alfa treatment, a significant increase of soluble TNF-R p75 always precedes the hepatitis B e antigen antibody against hepatitis B e antigen seroconversion in responders to treatment.
In chronic active hepatitis B infection, there is an up-regulation of the TNF receptor system, preferentially the TNF-R p75 signaling pathway, which suggests that the TNF-alpha/TNF receptor system has an important role in the pathogenesis of liver damage and viral clearance.
背景/目的：慢性乙型肝炎感染患者的血浆肿瘤坏死因子（TNF）α水平升高。已鉴定出两种TNF-α受体，每种受体负责不同的TNF-α活性。本研究的目的是通过检查乙型肝炎相关肝损伤演变过程中的两条TNF信号通路，评估慢性乙型肝炎病毒感染中升高的TNF-α的生物学功能。
测定了98例慢性乙型肝炎表面抗原携带者中两种TNF受体的肝脏表达以及两种受体可溶性形式的相应血清水平，并将其与肝脏炎症和病毒复制相关联。还对40例乙型肝炎e抗原阳性患者在接受干扰素α治疗期间进行了前瞻性研究，以检查病毒清除过程中TNF受体的反应。
在慢性乙型肝炎病毒感染中，TNF受体的肝脏表达和血清水平，特别是75千道尔顿TNF受体亚型（TNF-R p75），与肝脏炎症和肝细胞溶解相关显著增强，但与乙型肝炎病毒复制无关。在干扰素α治疗期间，可溶性TNF-R p75的显著增加总是先于治疗有反应者中乙型肝炎e抗原抗体对乙型肝炎e抗原的血清学转换。
在慢性活动性乙型肝炎感染中，TNF受体系统上调，优先上调TNF-R p75信号通路，这表明TNF-α/TNF受体系统在肝损伤发病机制和病毒清除中起重要作用。
