Investigation of Immunopathological Processes Associated with the Development of Liver Fibrosis

Abstract

The aim of this study was to determine the dependence of the course of liver fibrosis on the functional state of the immune system, in particular, on the imbalance of pro-inflammatory and anti-inflammatory immune reactions that are formed in patients during the development of the disease. The study included 30 patients with chronic liver diseases (18 patients with chronic hepatitis C (CHC) and 12 patients with alcoholic liver disease (ALD), 15 healthy individuals were the comparison group. Liver elastography (FibroScan) was used to evaluate liver stiffness and determine fibrosis stages according to METAVIR classification. The following cytokine levels were measured in the serum samples of the group: IL-1β, TNF-α, IL-6, IFN-γ, IL-2, IL-4, IL-8, VEGF and TGF-β. According to the data presented in this work, in patients with CHC and ALD, there was a statistically significant increase in serum levels of pro-inflammatory cytokines, namely: IL-1β, TNF-α, IFN-γ, IL-2, IL-6 and IL-8. Interestingly, elevated TGF-β values were found in patients with CHC, but not in patients with ALD. Significantly lower concentrations of VEGF were observed in both study groups. There was also a significant decrease in serum IL-4 in patients with CHC, whereas in patients with ALD such a decrease was not statistically significant. Serum IL-1β content was approximately equally elevated in the early and late stages of fibrosis. A sharp rise in serum TNF-α levels occurred in the early stages of fibrosis. In the later stages, the rise in the level was replaced by a sharp fall. However, the serum levels of TNF-α in the later stages of liver fibrosis still significantly exceeded control values. The serum levels of IFN-γ in patients significantly exceeded control values without changes in different stages of fibrosis. Relatively high levels of serum IL-2 and IL-6 were noted only in the later stages of the disease. In both groups of patients, a clear dependence of serum levels of IL-8 on the stage of fibrosis was revealed. Analysis of the data allows us to conclude that immune mechanisms play a significant role in the pathogenesis of degenerative liver diseases. Therefore further studies of the mechanism and role of immune factors is required to explore possible diagnostic and therapeutic applications.