The characteristics of immune status and carbohydrate metabolism at different stages of liver fibrosis in patients with hepatitis C virus-related chronic hepatitis

Abstract

Background. The article deals with the relationship between structural changes in the liver and immunological parameters in patients with chronic hepatitis C virus (HCV). The purpose of the study is to define the peculiarities of changes in the immune status and carbohydrate metabolism in patients with chronic HCV depending on the stage of fibrosis. Materials and methods. The research involved 94 patients with chronic HCV who were undergoing treatment at the Department of Liver and Pancreatic Diseases of the State Institution “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”. The diagnosis was verified on the basis of a thorough analysis of complaints, medical history, serological methods, ultrasound results, shear wave elastography, liver steatometry and morphological studies, in accordance with the recommendations of international consensus. Then these measurements were used to determine the average values that characterized the liver stiffness in kilopascals. Forty-two patients underwent a morphological examination. To study the associations of immunological status and carbohydrate metabolism with structural liver changes, all patients were divided into groups: moderate (FI + FII) and severe fibrosis (FII + FIV) according to METAVIR score. The subpopulation composition of lymphocytes was determined using the monoclonal antibodies (Sorbent TM) to molecules CD3, CD19, CD4, CD8, CD16. The immune status assessment was performed accor­ding to the guidelines of R.V. Petrov (1992). The level of circula­ting immune complexes was determined by the method of V. Haskov (1977). During the investigation, sets of reagents of Vector-BEST company were used to measure the amount of tumor necrosis factor α (TNF-α), interleukins (IL) 6 and 10, and those manufactured by DRG (Germany) — to measure insulin in the blood serum. The enzyme-linked immunosorbent assay was performed using Stat Fax 303 Plus analyzer (USA). The insulin resistance was evaluated using the homeostasis model assessment. Statistical processing of the results was performed using the software package Statistica 6.1 (serial number AGAR909 E415822FA). Results. According to shear wave elastography results, moderate fibrosis was diagnosed in 66 (70.2 %) patients with chronic HCV, and 28 (29.8 %) patients de­monstrated severe fibrosis. As a result of the investigation performed, the obtained data showed that in 73.4 % (69 of 94 cases) of patients with the chronic HCV, the content of CD3+ lymphocytes reduced relatively. The median of the relative CD4+ lymphocyte content decreased significantly — by 1.4 times (p < 0.05) as compared to the control group. The results of the correlation study showed that in patients with chronic HCV, CD4+ cells stimulated the production of antibodies by B-lymphocytes (r = 0.56, p < 0.01) and activated CD8+ T-cells (r = 0.59, p < 0.01) specific to virus-infected cells. The immunoregulatory index impairment (decrease) was found in 79.8 % of cases (75 of 94 patients). Individuals with chronic HCV were found to have a negative plausible correlation between T-hel­per content and liver stiffness (r = –0.26, p < 0.05). In addition, a probable increase in insulin content was found in chronic HCV patients with severe fibrosis, by 2.3 times in relation to its level in the control group (p < 0.05), and in patients with moderate fibrosis — by 1.3 times (p < 0.05). According to shear wave elastography data, a correlation was reported between this index and liver stiffness (r = 0.43, p < 0.05). Thus, in patients with chronic HCV, a correlation was established between IL-6 and: the liver stiffness according to shear wave elastography (r = 0.68, p < 0.01), the fibrosis stage according to METAVIR score (r = 0.57, p < 0.01). These data indicate that certain immunological indicators (B-lymphocyte, T-helper, TNF-α, IL-6 and insulin contents) can be used to develop non-invasive ­diagnosis of moderate and severe liver fibrosis in patients with chronic HCV. Conclusions. In patients with chronic HCV, the progression of liver fibrosis is accompanied by the depletion of the cellular immune system, increased levels of proinflammatory cytokines and impaired carbohydrate metabolism depending on the severity of fibrotic transformation.