Intrahepatic immune cell population in relation to liver damage and viral antigens in the context of Chronic Hepatitis B Virus Infection.

C GIADANS, D RÍOS, B AMEIGEIRAS, S FRÍAS, C VISTARINI, JM ROMEO, A PIETRANTONIO, N LUCATELLI, L HADDAD, O GALDAME, E MULLEN, F HEINRICH , ; E DE MATTEO; D FLICHMAN; P VALVA; M V PRECIADO

Taormina

Congreso; 2018 International HBV Meeting, The Molecular Biology of Hepatitis B Viruses; 2018

In Chronic Hepatitis B (CHB) infection, immune response is thought to be responsible for pathogenesis while viral proteins may have tolerogenic functions. But, the impact of the local infiltrate has not been fully explored. Our aim was to analyse the interplay between the immune response and viral activity in the context of liver damage.Immunostaining was performed in 31 liver biopsies from untreated adult patients with CHB (38% HBeAg+) to:1) characterize infiltrate [Th (CD4+), Th1(Tbet+), Th17 (IL-17A+), Treg (FoxP3+), and CTL (CD8+)] [portal quantification: positive/total lymphocytes; lobular quantification: positive lymphocytes/field, 10 fields; (400x)], 2) determine HBsAg and HBcAg expression. Inflammatory activity and fibrosis were assessed using the modified Knodell scoring and METAVIR. All studied populations were identified in portal/periportal infiltrates (P/P) with predominance of Th population. But, CTLs were the only one observed in the intralobular area. Regarding liver damage, Th and intralobular CTL were increased among severe hepatitis cases (p=0.002 and p=0.026; respectively) while, concerning fibrosis only Th17 depicted association with severe stages (p=0.033). An interesting finding was the mutually exclusive pattern expression of HBsAg or HBcAg (p=0.0006) being the presence of HBcAg related to severe hepatitis status (p=0,0023) and a higher frequency of Treg (p=0.001). Additionally, HBsAg was detected in biopsies with the lowest frequency of Th cells (p=0.003). Finally, there was an association between serological HBeAg+ cases and the intrahepatic detection of HBcAg (p=0.001) which also exhibit higher Treg frequency (p=0.0004).CHB infection showed a dynamic relation between the virus and local immune population which determines a distinctive antigen profile expression that could be reflecting different stages of viral replication and damage process. The presence of hepatic HBcAg might be an indicator of viral activity (HBeAg+) and inductor of a regulatory microenvironment. Meanwhile, Th17 population seemed to have a key role in fibrosis generation while presence of CTLs in the intralobular area denotes their contribution to hepatitis severity.