Chronic hepatitis B and chronic hepatitis C immunophatogenesis: Similar but not the same

Abstract

HBV and HCV are hepatotropic viruses which differ in the way they induce chronic disease. We aimed to compare the hepatic immune response in Chronic Hepatitis B (CHB) and C (CHC) infections and assess their role in liver damage. Immunostaining was done in 68 formalin-fixed and paraffin-embedded liver biopsies from 26 CHB and 42 CHC treatment-naive patients to characterize liver infiltrate: [Th (CD4+), Th1 (Tbet+), Th17 (IL-17A+), Treg (Foxp3+), and CTL (CD8+)]. Quantification: portal (P)= +/total lymphocytes or lobular= + lymphocytes in 10 fields; (400x). Hepatitis severity and fibrosis were assessed by the modified Knodell (HAI) and METAVIR. Comparing CHB and CHC lymphocyte prevalence was alike in P areas (Th>CTL>Treg>Th17>Th1). However, CHC patients showed higher frequencies of Treg, Th17 and Th1 cells (p=0.001, p=0.005 and p=0.003, respectively, U-test). In contrast, cell distribution was different in the lobular area (CHB: CTL> Treg>Th17=Th1>Th vs CHC: CTL>Th1>Treg>Th=Th17) with higher frequencies of Th, Th17 and Th1 cells in CHC (p=0.04, p=0.001 and p=0.001, respectively, U-test) compared with CHB. Regarding liver damage, patients with analogous disease stage showed similar cell frequencies but only in CHC P Th17 were associated with advanced fibrosis (p=0.03, U-test) and just in CHB P Th (p=0.04, U-test) and lobular CTLs and Th17 cells (p=0.02 and p=0.01, respectively; U-test) were increased in severe hepatitis cases.Even when all studied populations were identified in CHB and CHC, common and particular features related to liver damage were detected. Lobular CTLs prevalence in both infections implies their contribution in hepatitis pathogenesis. As for CHB, despite the presence of a regulatory microenvironment, CTLs and Th17 cells promote hepatitis severity, suggesting a Treg failure in limiting liver damage but favouring viral persistence. By contrast, CHC showed a highly inflammatory context with CTL and Th1 majority and Th17 cells enhancing liver fibrosis.