?The interplay between intrahepatic lymphocyte populations and Hepatitis B virus antigens related to liver damage in chronic hepatitis?

GIADANS C; RIOS D; AMEIGEIRAS B; FRIAS S; VISTARINI C; ROMEO JM; PIETRANTONIO AM; LUCATELLI NL; HADDAD L; GALDAME O; MULLEN E,; DE MATTEO E; FLICHMAN D; VALVA P; PRECIADO MV

Madrid

Congreso; ?28th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID)?; 2018

European Congress of Clinical Microbiology and Infectious Diseases (ECCMID)

During Chronic Hepatitis B (CHB) virus infection, the adaptive immune response is thought to be responsible for disease pathogenesis while viral proteins seemed to regulate it. Nevertheless, the impact of each immune cell population in liver damage and viral surveillance is still poorly understood.Our aim was to evaluate the influence of the immune response on viral activity in the context of liver damage in CHB.Immunostaining was performed in 23 liver biopsies from untreated adult patients with CHB (40% HBeAg-positive) to: 1) characterize liver infiltrate [Th (CD4+), Th1 (Tbet+), Th17 (IL-17A+), Treg (FoxP3+), and CTL (CD8+)] [portal quantification: immunostained/total lymphocytes; lobular quantification: immunostained lymphocytes/field, considering 10 fields; (400x)], 2) determine Hepatitis B surface antigen (HBsAg) expression. Inflammatory activity and fibrosis were assessed using the modified Knodell scoring system (Histological Activity Index, HAI) and METAVIR. All studied populations were observed in portal/periportal infiltrates with predominance of Th {Th [0.71 (0.39-0.89)] > CTL [0.58 (0.16-0.74)] > Treg [0.09 (0.00-0.25)] > Th1 [0.08 (0.00-0.20)] > Th17 [0.04 (0.00-0.20)]} yet, only CTLs were present in the intralobular area [2.00 (0.50-12.9)]. Regarding hepatitis severity, Treg and intralobular CTL populations were increased among severe hepatitis cases (p=0.035 and p=0.013; respectively), while, concerning fibrosis only Th17 cells depicted association with severe stages (p=0.020). According to HBV antigen profile, only 58% of the biopsies showed presence of hepatic HBsAg being its absence associated with severe hepatitis status (p=0.005) and with higher frequency of both Treg and intralobular CTL cells (p=0.007 and p=0.030). Moreover, serological HBeAg-positive cases exhibit higher frequency of Th cells (p=0.013) due to Treg population (p=0.001). Finally, there was an association between HBe Ag-positive cases and the absence of hepatic HBs Ag (p=0.015).Th17 population seemed to have a key role in fibrosis generation despite their low frequency. Meanwhile, intralobular CTLs denote their contribution to hepatitis severity. Due to the association between HBsAg and HBeAg, we theorise that the absence of hepatic HBsAg might be an indicator of active viral replication. Regarding this observation, our results suggest that the presence of a regulatory microenvironment might impair CTLs activity which in turn allows viral replication.