Markers of progression of liver fibrotic changes in patients with chronic toxic drug-induced hepatitis

Abstract

Background. In recent years, as a result of the growing expansion of the pharmaceutical market, there has been a clear trend towards an increase in the incidence of chronic toxic drug-induced hepatitis of drug genesis (TDIH). The appearance of fibrosis is considered the most important histological change that determines the further course of the disease. Therefore, the search for non-invasive or minimally invasive markers for assessing fibrotic changes in the liver remains an urgent issue in clinical practice. The purpose was to determine the diagnostic value of immunological parameters for stratification of the severity of liver fibrosis in patients with TDIH. Materials and methods. The study included 41 patients with TDIH, who were divided into three groups: group I consisted of 12 people without liver fibrosis (F0), group II — 22 patients with moderate fibrosis (F1-F2), group III — 7 individuals with severe liver fibrosis (F3-F4). Shear wave elastography was performed using a Soneus P7 system (Ukraine-Switzerland). All patients underwent a biochemical blood test with the determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST). The subpopulation composition of lymphocytes, circulating immune complexes (CIC), the level of interleukins (IL-6, IL-10) and tumor necrosis factor α were assessed. Results. The progression of liver fibrosis is accompanied by an increase in cytolytic syndrome: patients with severe fibrosis have a 3.3-fold increase in the ALT (p < 0.05) compared to the controls and a 2.1-fold (p < 0.05) compared to that in patients with moderate fibrosis. The AST level is significantly higher — by 4.6 times (p = 0.023) in patients with severe fibrosis than in those with moderate fibrosis. With the progression of liver fibrosis, there is a significant decrease in cellular immunity, an increase in the level of CIC and pro-inflammatory cytokines with a simultaneous decrease in the content of anti-inflammatory cytokines, which is confirmed by correlations between the liver stiffness index according to shear wave elastography data and the level of T-helpers (r = –0.466; p = 0.03), IL-6 (r = 0.364; p = 0.01), IL-10 (r = –0.331; p = 0.039) and CIC (r = 0.381; p = 0.017). Conclusions. Markers of the diagnosis of severe liver fibrosis in patients with TDIH are indicators such as the ratio of IL-6/IL-10 higher than 0.83 (sensitivity 81.8 %, specificity 78.9 %), CIC level more than 4.3 optical density units (sensitivity 77.3 %, specificity 72.2 %), the ratio of T-helpers/T-suppressors is less than or equal to 1.6 (sensitivity 72.7 %, specificity 57.9 %).

Diagnostic values of MMP-9 and TGF-1β in assessing the severity of liver fibrosis and the rate of its progression in patients with chronic hepatitis C GT 1 infection

“…The analysis of literature data focused on the search for informative serum markers to diagnose severe liver fibrosis has shown that it was reasonable to use different serum markers in chronic diffuse liver diseases of different etiology. So, the study [20] has shown that the most informative serum markers for the diagnosis of severe liver fibrosis in patients with chronic alcoholic hepatitis were levels of tumor necrosis factor-α >2.1 pg/ml and protein-bound hydroxyproline >260.5 μmol/l. Another study [21] has shown a number of parameters, in particular, HBeAg status, viral load, the degree of necroinflammatory activity expressiveness according to alanine aminotransferase indicators, and the degree of tumor necrosis factor-α increase, that should be considered when assessing a risk of severe liver fibrosis in chronic hepatitis B.…”

Immunophysiological State of Dogs According to the Immunoregulatory Index of Their Blood and Spleens

“…Thus, in rats with acute periodontitis, its value increases compared to intact animals; in rats with hypothyroidism, it decreases, and in animals with simultaneous manifestation of acute periodontitis and hypothyroidism, the IRI significantly decreases [ 25 ]. The IRI is reduced in patients with non-alcoholic fatty liver disease and chronic hepatitis C. However, in patients with non-alcoholic fatty liver disease, the content of CD8 lymphocytes does not change [ 26 ]. The authors’ research also revealed a relationship between the absolute number of leukocytes, lymphocytes, phagocytic activity, and the IRI [ 27 ].…”