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.