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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Gregor Ebert; Simon Preston; Cody Allison; James Cooney; Jesse G Toe; Michael D Stutz; Samar Ojaimi; Hamish W Scott; Nikola Baschuk; Ueli Nachbur; Joseph Torresi; Ruth Chin; Danielle Colledge; Xin Li; Nadia Warner; Peter Revill; Scott Bowden; John Silke; C Glenn Begley; Marc Pellegrini Journal: Proc Natl Acad Sci U S A Date: 2015-04-20 Impact factor: 11.205
Authors: B Kallinowski; K Haseroth; G Marinos; C Hanck; W Stremmel; L Theilmann; M V Singer; S Rossol Journal: Clin Exp Immunol Date: 1998-02 Impact factor: 4.330
Authors: E Redondo-Cerezo; F Casado-Caballero; J L Martin-Rodriguez; J Hernandez-Quero; F Escobar-Jimenez; J L Gonzalez-Calvin Journal: Osteoporos Int Date: 2014-03-28 Impact factor: 4.507
Authors: Nancy Gasper-Smith; Deanna M Crossman; John F Whitesides; Nadia Mensali; Janet S Ottinger; Steven G Plonk; M Anthony Moody; Guido Ferrari; Kent J Weinhold; Sara E Miller; Charles F Reich; Li Qin; Stephen G Self; George M Shaw; Thomas N Denny; Laura E Jones; David S Pisetsky; Barton F Haynes Journal: J Virol Date: 2008-05-28 Impact factor: 5.103