Host Immune Responses Determine the Natural Course and Treatment Response of Chronic Hepatitis B as well as Hepatocellular Carcinoma

• Main Authors: I-Cheng Lee, 李懿宬
• Other Authors: Yi-Hsiang Huang
• Format: Others
• Language: en_US
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/40223312398599389681

博士 === 國立陽明大學 === 臨床醫學研究所 === 103 === Host immunity is believed to play important roles in the pathogenesis of chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC). Currently, whether IL28B genotypes are associated with the natural course of hepatitis B virus (HBV) infection and hepatitis activity in CHB is not fully understood. The first part of this study aimed to investigate the role of viral and host factors, including IL28B genotypes, in the natural course of CHB. By analyzing consecutive 115 treatment-naive CHB patients, we showed that HBV viral load and IL28B rs10853728 CC genotype correlated with hepatitis activity in HBeAg-positive and HBeAg-negative CHB, respectively. Therefore, both viral and host immune factors play roles in disease activity during different phases of CHB. Pre-treatment and on-treatment predictors of virological response in CHB patients under pegylated interferon-alpha (PEG-IFN) therapy remain unsatisfactory to meet clinical need. In the second part of study, we prospectively investigated the baseline and on-treatment immunological and viral predictors of virological response in 74 CHB patients receiving PEG-IFN treatment. Our results showed that pre-treatment chemokine CXCL9 level significantly correlated with virological response. The performance of CXCL9 in predicting virological response was good, particularly in HBeAg-negative patients with low viral loads (positive predictive value = 64.3%). CXCL9 might reflect host immune response against HBV and could be a potential marker to predict treatment response for CHB. Recent studies also demonstrate that an immunosuppressive status is associated with advanced stage of HCC through the effect of regulatory T cells (Tregs) and the secretion of TGF-β. This finding supports the concept that cancer would impair host immunity. It is unclear whether host immunity is also a factor related to tumor recurrence after curative treatment. In the third part of this study, we prospectively evaluated the baseline and early predictors of tumor recurrence by testing several immune markers from peripheral blood in 63 HCC patients, including serum levels of IL-10, TGF-β, IFN-γ, IP-10, and the prevalence of Tregs, NK+ T cells, invariant NKT cells, PD-1+CD8+ T cells, T helper 17 cells, CD69+ and CD45RO+ T cells in peripheral blood mononuclear cells. Our results showed that patients with lower levels of IFN-γ prior to treatment have higher risk of recurrence. Serum levels of IFN-γ also correlated with tumor size and stage. Therefore, IFN-γ may reflect host anti-tumor immunity and may be a potential marker of HCC recurrence after curative treatment. In conclusion, host immunity may play important roles in the natural course of CHB, and may determine the treatment response of both CHB and HCC. The immunological biomarkers can also be served as predictors of treatment response in CHB and HCC.