Arthrospira Enhances Seroclearance in Patients with Chronic Hepatitis B Receiving Nucleos(t)ide Analogue through Modulation of TNF-α/IFN-γ Profile

Abstract

Chronic hepatitis B (CHB) virus infection, causing immune dysfunction and chronic hepatitis, is one of the leading risk factors for hepatocellular cancer. We investigated how Arthrospira affected hepatitis B surface antigen (HBsAg) reduction in CHB patients under continued nucleos(t)ide analogues (NA). Sixty CHB patients who had been receiving NA for at least one year with undetectable HBV DNA were randomized into three groups: control and oral Arthrospira at 3 or 6 g daily add-on therapy groups. Patients were followed up for 6 months. Oral Arthrospira-diet mice were established to investigate the possible immunological mechanism of Arthrospira against HBV. Within 6 months, mean quantitative HBsAg (qHBsAg) decreased in the oral Arthrospira add-on therapy group. Interestingly, interferon gamma (IFN-γ) increased but TNF-α, interleukin 6 (IL-6), hepatic fibrosis, and steatosis decreased in the add-on groups. In mice, Arthrospira enhanced both innate and adaptive immune system, especially natural killer (NK) cell cytotoxicity, B cell activation, and the interleukin 2 (IL-2), IFN-γ immune response. Arthrospira may modulate IL-2- and TNF-α/IFN-γ-mediated B and T cell activation to reduce HBsAg. Also, Arthrospira has the potential to restore immune tolerance and enhance HBsAg seroclearance in CHB patients through promoting T, B, and NK cell activation.

The Important Roles of Natural Killer Cells in Liver Fibrosis

“…In clinical trials, some treatments have been evaluated to treat liver diseases by regulating NK cell frequency and function, including lipid-lowing agents (e.g., rosuvastatin) [104], immune regulators (e.g., Toll-like receptor 8 agonist GS-9688) [114,115], antiviral agents (e.g., pegylated interferon-alpha) [116][117][118], anticancer agents (e.g., Sorafenib) [119], mi-croRNAs (e.g., RG-101) [120], and combined therapies (e.g., IL-2 and IFN) [121], as well as organisms (e.g., Arthrospira, a genus of free-floating filamentous cyanobacteria) [122]. In Table 2, we review the functions of different treatments in NK cell regulation.…”

“…Treatment with Arthrospira, a genus of free-floating filamentous cyanobacteria, increased serum IFN-γ levels but decreased serum TNF-α and IL-6 and hepatic fibrosis and steatosis in CHB patients receiving NA therapy. [122] Abbreviations: CHB: chronic hepatitis B (CHB); HBeAg: hepatitis B e antigen; HBsAg: hepatitis B surface antigen; IFN: interferon; PBMCs: peripheral blood mononuclear cells; TLR-8: Toll-like receptor 8.…”

Natural Compounds and Healthy Foods: Useful Tools against Onset and Progression of Chronic Diseases

“…Furthermore, oral Arthrospira -diet mice were also used to investigate the possible immunological mechanism of Arthrospira against the hepatitis B virus. The study results showed that Arthrospira treatment can reduce HBsAg and rejuvenate the immune tolerance in CHB patients, by inducing B, T, NK, and macrophage cell activation [ 15 ].…”