Hepatitis B virus infection and interferon-inducible protein-10

Interferon (IFN)-inducible protein-10 (IP-10) is a proinflammatory chemokine, binding the chemokine (C-X-C motif) receptor 3 (CXCR3), which is found mainly on activated T cells and natural killer (NK) cells, and plays an important role in T helper (Th) 1 type inflammatory disorders (autoimmune, neoplastic, and infectious diseases). Concerning viral hepatitis, IP-10 appears to be involved on the pathogenesis of liver damage as well as on the extra-hepatic manifestations either protecting or promoting infection, depending on host immune status and genetic background. During chronic hepatitis B, IP-10 is specifically produced by hepatocytes in inflammatory areas. Here, IP-10 leads to recruitment of T cells, production of IFN-gamma by activated NK T cells, and then monokine induced by IFN-gamma (MIG) and IP-10 secretion by parenchymal and non-parenchymal cells, with a final positive feedback, perpetuating the immune cascade. The increased levels of IP-10 and IP-10 mRNA in the peripheral blood of patients with cirrhosis are closely correlated with the load of HBV DNA in serum, and seem to play a key role in the progression of post-hepatitic cirrhosis. Higher pre-treatment IP-10 levels, and dynamic down-regulation, are associated with an increased probability of hepatitis B e antigen (HBeAg) loss after Peg-IFN therapy. Hepatitis B surface antigen (HBsAg) drop in patients treated with nucleos(t)ide analogues (NAs) is associated with higher baseline IP-10.