Impact of immune cell, state of cytokine regulation and intestinal biocenosis on the fibrotic processes in chronic diffuse liver disease

Abstract

Background. It is known that disorders of the intestinal microbiota in patients with chronical liver disease (CLD) are associated with immune dysregulation. The process begins with a violation of the intestinal microbiota, leading to the development of immunodeficiency, affecting the course of the underlying disease (with progression of liver fibrosis). Besides, violation of intestinal biocenosis is a consequence of adverse effects on the body and its microflora state resulting in reduced immune function. The purpose of the study was to determine the mechanisms of cytokine regulation in the body of patients with CLD in the formation and progression of liver fibrosis depending on the damage of the intestinal microbiota. Materials and methods. Seventy-six patients with CLD were examined. All patients underwent a hydrogen breath test (HBT), shear wave elastography; the liver stiffness parameters were studied on a FibroScan. Depending on the indices obtained and the presence of small intestinal bacterial overgrowth (SIBO) in the small intestine in the formation and progression of liver fibrosis, the patients were divided into groups. The subpopulation of lymphocytes — CD4 and CD8 was determined using monoclonal antibodies from the company “Sorbent TM”. The serum level of IL-6, IL-10, TNF-α was determined by enzyme-linked immunosorbent assay (ELISA) using the reagent kits from the company “Vector-BEST”. Results. The elevated levels of inflammatory cytokines (IL-6 and TNF-α) do not induce the secretion of anti-inflammatory cytokines (IL-10) with the presence of SIBO, which leads to the maintenance of inflammation and progression of liver fibrosis depending on intestinal biocenosis (a correlation was found between liver stiffness and hydrogen levels r = 0.79; р < 0.001). In patients with CLD, the violation of the cellular component of immunity is associated with an impairment of the intestinal microbiota, as evidenced by correlations with the hydrogen level (ppm): CD8+ (r = –0.439; p < 0.05) and CD4/CD8 (r = +0.492; p < 0.05). Conclusions. Impaired immunoregulatory mechanisms contribute to the fibrotic processes with subsequent violation of the gut microbiota.

Keywords

• immunoregulation, inflammatory process, liver fibrosis, intestinal microbiota, syndrome of intestinal bacterial overgrowth, inflammatory and anti-inflammatory cytokines, chronic diffuse liver disease