Abstract
Background & AimsThe natural course of chronic hepatitis B virus (HBV) infection is characterized by different immune responses, ranging from immune tolerant (IT) to immune activated (IA) stages. In our study, we investigated the natural killer (NK) cells activity in patients at different immunological stages of chronic HBV infection.MethodsBlood samples obtained from 57 HBeAg positive patients with chronic hepatitis B (CHB), including 15 patients in the immune tolerant (IT) stage, 42 patients in the immune activated (IA) stage, and 18 healthy individuals (HI). The analyses included flow cytometry to detect NK cells, the determination of cytokine levels as well as of surface receptor expression and cytotoxicity.ResultsNK cells in peripheral blood were significantly lower in patients in the IA stage of CHB compared to HI (p<0.05). Patients in the IA stage of CHB had lower levels of NK cells activating receptor NKp30 and NKG2D expression, cytokine interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) production, as compared to patients in the IT stage and HI, respectively (p<0.05). Cytotoxicity of NK cells was lower in patients in the IA stage of CHB compared to patients in the IT stage and HI, respectively (p<0.05). The level of IFN-γ but not level of TNF-α and cytotoxicity of NK cells was inversely correlated with serum HBV load in patients with CHB. Peripheral NK cells activity did not correlate with ALT level.ConclusionNK cells activity was lower in CHB patients, especially in those in the IA stage.
Highlights
Hepatitis B virus (HBV) infection is a leading cause of liver diseases worldwide, especially in Asia and is associated with a wide spectrum of clinical manifestations, ranging from an asymptomatic course to active hepatitis B with progression to liver cirrhosis and hepatocellular carcinoma (HCC).While hepatitis B virus (HBV) is not directly a cytopathic, the pathogenesis of HBV-related liver disease is immune mediated
We found that natural killer (NK) cells activity is decreased in patients with chronic HBV infection, especially in patients in the immune activated (IA) stage
Peripheral blood monouclear cells (PBMCs) subsets in patients with chronic HBV infection CD32CD56+ NK cells, CD4+ T cells and CD8+ T cells have all been shown to be involved in the antiviral immune response [30,31]
Summary
Hepatitis B virus (HBV) infection is a leading cause of liver diseases worldwide, especially in Asia and is associated with a wide spectrum of clinical manifestations, ranging from an asymptomatic course to active hepatitis B with progression to liver cirrhosis and hepatocellular carcinoma (HCC).While HBV is not directly a cytopathic, the pathogenesis of HBV-related liver disease is immune mediated. The natural course of chronic HBV infection can present as different immunological stages, including immune tolerance and immune activation. The immune tolerant (IT) stage is characterized by HBeAg positivity, high levels of serum HBV DNA, normal serum alanine aminotransferase (ALT) levels and normal or minimally abnormal liver histology [2,3]. The immune activated (IA) stage is characterized by low levels of serum HBV DNA, elevated ALT levels, and active inflammation and even fibrosis in liver tissue [2,3]. The natural course of chronic hepatitis B virus (HBV) infection is characterized by different immune responses, ranging from immune tolerant (IT) to immune activated (IA) stages. We investigated the natural killer (NK) cells activity in patients at different immunological stages of chronic HBV infection
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