Chronic hepatitis B: The interplay between intrahepatic lymphocyte population and viral antigens in relation to liver damage.
In Chronic hepatitis B (CHB) infection, virus and immune response interplay is thought to be responsible for pathogenesis. Yet, the impact of each immune cell population and viral protein expression in liver damage is still unknown. Our aim was to study the interplay between intrahepatic immune response and viral activity in relation to CHB liver damage. Immunostaining was performed in 29 liver biopsies from untreated CHB patients to characterize liver infiltrate [Th (CD4+), CTL (CD8+), Treg (FoxP3+), Th17 (IL-17A+) and Th1 (T-bet+)] and viral antigen expression (HBsAg and HBcAg). Inflammatory activity and fibrosis were assessed using the HAI and METAVIR scoring system. All studied populations were identified in the portal-periportal (P-P) areas with a CD4+ lymphocyte predominance, while only CD8+ and FoxP3+ cells were observed in the intralobular area. Both P-P CD4+ and intralobular CD8+ cell frequencies were increased among severe hepatitis cases. Concerning HBsAg and HBcAg expression, a mutually exclusive pattern was observed. HBcAg was mainly detected among HBeAg-positive patients and was associated with hepatitis severity and higher frequency of P-P FoxP3+, intralobular CD8+ and FoxP3+ cells. HBsAg was identified among HBeAg-negative cases with less severe hepatitis grade and lower frequency of P-P CD4+ and intralobular FoxP3+ lymphocytes. In conclusion, the HBV antigen profile expression seen during CHB infection may be reflecting different stages of viral replication which impacts the host immune response and liver damage process. While HBcAg might be an inducer of a regulatory microenvironment, the intralobular CTL population seemed to have a key role in hepatitis severity.
['Giadans|Cecilia G|CG|0000-0002-3756-5975', 'Ríos|Daniela A|DA|', 'Ameigeiras|Beatriz|B|', 'Pietrantonio|Adriana M|AM|', 'Lucatelli|Néstor L|NL|', 'Haddad|Leila|L|', 'Mullen|Eduardo|E|', 'Heinrich|Fabiana|F|', 'De Matteo|Elena|E|', 'Flichman|Diego|D|', 'Valva|Pamela|P|', 'Preciado|María V|MV|']
D000328:Adult D000368:Aged D000956:Antigens, Viral D001706:Biopsy D015496:CD4-Positive T-Lymphocytes D018414:CD8-Positive T-Lymphocytes D005260:Female D006512:Hepatitis B Core Antigens D006513:Hepatitis B e Antigens D006515:Hepatitis B virus D019694:Hepatitis B, Chronic D006801:Humans D007150:Immunohistochemistry D007249:Inflammation D008099:Liver D016131:Lymphocyte Subsets D008297:Male D008875:Middle Aged D012189:Retrospective Studies D050378:T-Lymphocytes, Regulatory D055815:Young Adult
chronic hepatitis B viral antigen liver damage inflammatory infiltrate