TUMOR-NECROSIS-FACTOR RECEPTORS IN PATIENTS WITH CHRONIC HEPATITIS-B VIRUS-INFECTION

Background/Aims: Patients with chronic hepatitis B infection have elev ated plasma tumor necrosis factor (TNF) alpha levels. Two TNF-alpha re ceptors have been identified, each responsible for distinct TNF-alpha, activities. The aim of this study was to evaluate the biological func tion of the elevated TNF-alpha in chronic hepatitis B virus infection by examining the two TNF signaling pathways in the evolution of hepati tis 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 inf lammation and virus replication in 98 chronic hepatitis B surface anti gen 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 o f TNF receptors, in particular 75-kilodalton TNF receptor subtype (TNF -R p75), are significantly enhanced in association with hepatic inflam mation and hepatocytolysis but not with hepatitis B virus replication. During interferon alfa treatment, a significant increase of soluble T NF-R p75 always precedes the hepatitis B e antigen antibody against he patitis B e antigen seroconversion in responders to treatment. Conclus ions: In chronic active hepatitis B infection, there is an up-regulati on 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 .