Also in this line, innate immunity was found to be suppressed in advanced stages of liver fibrosis in an experimental mouse model of cirrhosis. Moreover, HEV by itself can contribute to a downregulation of immune activity. In this sense,PBOX-15 it has been reported that the protein encoded by HEV open reading frame 3 gene might reduce the host inflammatory response, even attenuating the acute phase reaction, further creating an environment favourable for viral replication. In fact, secretion of immunosuppressive a1-microglobulin was increased in HEV ORF3-protein expressing cells potentially resulting in a protection of of virus-infected cells. The additive effect of both factors, innate-immunity suppression in advanced liver fibrosis and the direct immunosuppresive effect of HEV, could explain the higher HEV infection susceptibility of LC patients in relation to other groups. Alternatively, HEV, which can evolve to chronicity in immunosuppressed patients, could be implicated in the pathogenesis of cirrhosis in this population, in whom a high percentage of patients are infected with HCV or HBV. However, anti-HEV seroprevalence was lower in patients coinfected with HCV than from the rest of liver disease aetiologies. Futhermore, in the multivariant analysis, hepatitis C infection was a protective factor for the presence of anti-HEV IgG. An explanation for this fact could be that treatment for chronic hepatitis C includes ribavirin,NSC73306 a therapy also effective against HEV. Concerning HIV-infected patients, this patient cohort was previously analysed but not compared with other inmunosupressed patients, this comparison has been performed in the present study. In this sense, hepatitis E seroprevalence in the HIV cohort was statistically higher than non-HIV population, a rate that increased when patients with CLD and particularly liver cirrhosis were analysed separately, being the IgG anti-HEV rate 10% and 22.7% respectively. In the literature, there are discrepancies with regards to the real seroprevalence of HEV in the HIV positive population and the possibility of a higher predisposition in this group to hepatitis E infection.