CHARACTERIZATION OF INTRAHEPATIC IMMUNE CELL POPULATION AND VIRAL ANTIGENS IN RELATION TO LIVER DAMAGE IN THE CONTEXT OF CHRONIC HEPATITIS B VIRUS INFECTION

VALVA P; HEINRICH F; PIETRANTONIO AM; RIOS D; PRECIADO MV; DE MATTEO E; HADDAD L; FLICHMAN D; AMEIGEIRAS B; MULLEN E; FRÍAS, SILVIA E.; GIADANS CG

Punta Cana

Congreso; XXV Congreso ALEH 2018; 2018

Asociación Latinoamericana para el Estudio del Hígado

In Chronic Hepatitis B (CHB), immune response is thought to be responsible for liver damage. In this scenario viral antigen expression may also have a key role in liver pathogenesis. We aimed to study the interplay between intrahepatic immune response and viral activity in relation to CHB liver damage.Immunostaining was performed in 31 liver biopsies from CHB untreated patients (38% HBeAg+) to characterize: 1) liver infiltrate [Th (CD4+), CTL (CD8+), Treg (FoxP3+), Th17 (IL-17A+) and Th1 (Tbet+)]. Quantification: portal area: positive/total lymphocytes, lobular area: positive lymphocytes/field in 10 fields; (400x)]; 2) HBsAg and HBcAg expression. Inflammatory activity and fibrosis were assessed using the HAI and METAVIR scoring system.All studied populations were identified in the portal/periportal areas with a Th cell predominance, while only CTLs were observed in the lobular area. Both portal/periportal Th and lobular CTL frequencies were increased among severe hepatitis cases (p=0.002 and p=0.01, respectively) while Th17 subset showed a trend of association with significant fibrosis (p=0.05). Concerning HBsAg and HBcAg expression, a mutually exclusive pattern was seen. HBcAg liver expression was related to serological HBeAg presence (p=0.001) and hepatitis severity (p=0.005). Moreover, HBcAg was associated with a higher frequency of Treg and lobular CTL (p=0.02 and p=0.04, respectively). HBsAg was detected in cases with the lowest Th cells count (p=0.003). Finally, HBeAg+ cases exhibited a higher frequency of Th (p=0.002) due to the Treg subpopulation (p=0.001).The HBV antigen profile expression seen during CHB infection may be reflecting different stages of viral replication and damage process. The presence of hepatic HBcAg might be an indicator of active viral activity and an inducer of a regulatory microenvironment. On the other hand, Th17 could be contributing to fibrosis generation while CTL population seemed to have a key role in hepatitis severity.