Abstract
BACKGROUND: Hepatitis B virus (HBV) replicates non-cytopathically in the hepatocytes and HBV-related diseases are caused by immune-mediated inflammatory events. This study aimed to identify the relationship between clinical-virological characteristics and immunity in untreated chronic hepatitis B (CHB) patients. METHODS: A total of 209 CHB patients were categorized into immune tolerant (IT, n = 17), inactive carrier (IC, n = 20), immune active (IA, n = 120), and gray zone (GZ, n = 72) phases. The quantitative hepatitis B surface antigen (qHBsAg), hepatitis B e antigen (HBeAg), anti-HBeAg (HBeAb), HBV genotype, viral mutant and frequencies of interleukin (IL)-4, IL-17, IL-10 and interferon-gamma (IFN-γ) produced by CD4(+) and CD8(+) T cells were tested. We also correlated these cytokines with clinical-virological characteristics using a linear regression model. RESULTS: CD8(+) T cells frequency were significantly decreased in IT patients. Levels of CD4(+) T cells IL-4(+) or IL-10(+) were strongly negatively associated with qHBsAg titers. The frequency of IFN-γ produced by CD4(+) and CD8(+) T cells showed significant positive association with age and alanine aminotransferase (ALT) level, while that had negative association with qHBsAg titers. Additionally, the ratios of mutations in the HBV precore (PC) stop codon and basal core promoter (BCP) and the combined mutations were 32.5, 27.2, and 11.3%, respectively. The frequency of CD4(+) T cells IL-17(+) was higher in patients with a PC mutation than that in patients carrying a wild-type sequence. Finally, little associations among T cell derived IL-4, IL-10, IL-17, and IFN-γ was observed in the current untreated CHB cohort. CONCLUSIONS: Several components of the immune system were correlated with HBV factors that influence an inflammatory process during CHB. Of particular relevance are the significant associations of between CD4(+) T cells IL-4(+) and qHBsAg level, and between CD4(+) T cells IL-17(+) and the presence of a mutation in PC.