Prof. Szabo: The rule of the immunity in hep C infection is very important just like in any viral infection. In it that immunity is the first line of defense in the host immunity and if the innate immune response is not robust enough and does not start early enough then that itself can offset and lead to chronic infection. In case of innate immunity in hepatitis C infection, the induction of various interferons is a key step and that includes the type 1 interferons and also the induction of interferon that turns out is important in the early viral elimination and then of course the role of the innate immunities to trigger and induce a varied robust and adaptive immunity that is key in hep c viral elimination.
Prof. Szabo: Yes, there are multiple serum markers for innate immunity particularly various circulating cytokines and interferons. In the case of cytokines it has been shown that in hep c virus infection some of the pro inflammatory cytokines, in particular TNF and IL-1, and some of the chemokines are actually increased in the serum but that goes along with the chronic infection and inducing a chronic low grade inflammation. In these patients the levels of serum interferons is less reliable although it is known that low levels of interferon gamma can go along with chronic infection.
Prof. Szabo: I think that the fascinating and the clinically important discovery was the direct acting antivirals because those interfere with some of the mechanism by which hepatitis c undermines the host immune response. For example, the serum protease inhibitors in particular interfere now with the virus and prevent the virus serum protease inhibitors to cleave off some of the adaptor molecules that are involved in type 1 interferon induction in the host. That is a very important mechanism and by interfering with this, NS3 activity of the hepatitis C virus and some of the direct acting antivirals can allow the host immune response to actually work very effectively and similarly too for some of the NS5A, NS5B, and NS3 inhibitors that reduce viral replication and therefore enable innate immune response to trigger the host antiviral immunity.
Prof. Szabo: So certainly all the direct acting antivirals could directly improve host immune responses the same way as I alluded to earlier today by permitting the host immune response to act effectively. Another component that is not necessarily innate immunity but affecting host factors is the clinical trial with the micron A1 22 inhibitor considering that micron a1 22 is a host factor in the hepatocytes that promotes and is required for hep c viral replication.
Prof. Szabo: Well I think all of us in clinical hepatology hope that the new DAAs and combinations of these drugs will allow us to treat all patients who have chronic hep C v infection and I think it is a lofty goal but certainly it is a very enticing goal to eradicate hep C v around the world.