Liver immune microenvironment in the pathogenesis of chronic HBV and HCV infection: Th17/Treg interplay related to fibrosis.

DA. RIOS, C GIADANS, L HADDAD, S FRÍAS, C VISTARINI, E DE MATTEO, E MULLEN, P CASCIATO, B M. AMEIGEIRAS, JM. ROMEO, C BRODERSEN, D KRASNIANSKY, J BANDI, O GALDAME, D FLICHMAN, P VALVA, M V. PRECIADO

Washington DC

Congreso; The Liver Meeting- AASLD2017; 2017

Although the immune system is involved in liver injury both in chronic HBV and HCV hepatitis, the role of each immune component is still unknown. Our aim was to explore the intrahepatic T cells population, particularly the Th17/Treg interplay, regarding liver damage.Infiltrate characterization was performed in 43 formalin-fixed paraffin-embedded liver biopsies from untreated adult patients with chronic viral hepatitis (HCV=24, HBV=19) by immunohistochemistry/confocal immunofluorescence. The frequency of Cytotoxic T Lymphocytes (CTL, CD8), T helper cells (Th, CD4) and Th subsets [Treg (Foxp3), Th17(IL-17A), Th1(Tbet)] were quantified in portal/periportal areas [positive/total lymphocyte (400)]. Inflammatory activity and fibrosis were assessed using the modified Knodell scoring systemand METAVIR. In both groups Th cells [HCV: 0.72 (0.48-0.85), HBV: 0.71 (0.46-0.89)] count was higher than CTL count [HCV: 0.52 (0.31-0.75), HBV: 0.59 (0.16-0.74)], with Th17 cells being the less frequent Th subset [HCV: Treg 0.16(0.02-0.29),Th1 0.14(0.03-0.39),Th17 0.08(0.01-0.26); HBV: Treg 0.10(0.0-0.25),Th1 0.07(0.0-0.20),Th17 0.04(0.0-0.14)]. When comparing both groups, higher frequencies of Th subsets were found in the HCV group(Treg:p=0.049, Th1:p=0.015, Th17: p=0.017, Mann-Whitney test), although the Th17/Treg ratio was similar. Concerning liver damage both groups are homogeneous(HCV: 62% significant fibrosis, 75% moderate/severe HAI; HBV:42% significant fibrosis,55% moderate/severe HAI; pfibrosis=0.34, Fisher test; pHAI=0.38, Chi-squaretest). In the HCV group, lower frequencies of Treg cells but higher of Th17 were observed in cases with severe fibrosis (p=0.038, T test; p=0.013, Mann-Whitney test, respectively), and Th17/Treg cell ratio was associated with advanced fibrosis (p=0.024, Mann-Whitneytest). In HBV group Th17 cells depicted positive association with fibrosis severity (p=0.004, T test). Finally, in both studied groups no lymphocyte population displayed association with hepatitis severity.Pathogenesis of viral hepatitis is a complex process where the immune component is crucial. Of note,given the antagonist functions of Tregs and Th17 cells, dynamic change in their frequencies as well as in the Th17/Treg balance may be associated with liver pathogenesis. Our results suggested that intrahepatic Th17 cells participates in fibrogenesis in both, chronic HBV and HCV infections, while Treg seems to have a protective role in HCV pathogenesis. Although the immune scenario against both viral infections is supposed to be different, our results interestingly highlight that the interplay between Th17 and Treg conditioned fibrogenesis.