International Medical Journal, Vol. 21., Iss. 3, 2015, P. 81−87.
THE FEATURES OF IMMUNE REGULATION IN PATIENTS WITH HCV INFECTION
V. N. Karasin Kharkiv National University, Ukraine
Infectious hepatitis is a serious problem which is still unsolved. According to the WHO data there are millions of infected people with infectious hepatitis throughout the world. Nowadays potential of infectious hepatitis C (IHC) is still high. Wide spread of hepatitis C among the cases of viral hepatitis has also been established in Ukraine. The number of infected people reaches 170−500 mln in the world. The urgency of HCV problem is characterized by the threat of chronization with forming chronic hepatitis, cirrhosis and in some cases of hepatocellular carcinoma. Most of the researchers consider that cooperation of the virus and human immune system is one of the basic factors which determine subsequent manifestation of HCV−infection. It is known that elimination of viruses from the human organism is provided by an adequate immune response and insufficient intensity of immune inflammation which leads to persistence of viral infection. We observed the group of 155 patients treated in Kharkiv Regional Clinical Infectious Hospital with the diagnosis of acute (37) and chronic hepatitis C (118). Clinical investigations, laboratory blood and urine tests, blood biochemistry; ultrasonography of the abdominal region and liver puncture biopsy and some additional examinations were performed. To study the properties of HCV infection the following laboratory methods were used: IEA to identify specific markers of HCV (anti−HCV IgМ, anti−HCV IgG, anti−HCVcore/NS−3, −4, −5) in the blood, to identify HCV RNA. To determine genotypes of HCV, the method of direct sequencing and restriction analysis was used. To identify cytokins, IEA were used. The level of subpopulation of lymphocytes in immunograms was investigated with monoclonal antibodies. Clinical and pathogenic role of the changes in immunoregulation in patients with hepatitis C was studied. The role of integrated analysis of cell and secretory immunity indices, the role of immune response mediator changes in evaluation of corresponding organism reaction against HCV−infection, prognosis of severity and consequences of the disease were shown. Immune status changes regarding virus genotype, course, replicative and biochemical activity were analyzed. Criteria of the course prognosis and outcomes of acute hepatitis C were worked out. The presence in the peripheral blood of patients of anti−HCV NS3 and absence of anti−HCV NS4, anti−HCV NS5 are an important diagnostic criterion of acute hepatitis C (AHC). The presence in the peripheral blood of patients of anti−HCV NS4, anti−HCV NS5 can be used as a marker of chronic HCV infection (ChHC). Immune disorders in patients with AHC during the height of the disease are characterized by imbalance of cellular and humoral immuneregulation, manifested by decreasing of CD3+, CD4+, hyperproduction of CD16+, CD20+, CD25+ −lymphocytes, total IgM. At the same time there are changes in cytokine status, characterized by increase in TNF−?, IFN−?, IL−2, IL−4, and IL−10. The period of clinical and biochemical remission compared with the height of the AHC in most patients is characterized by a decrease of CD16+− lymphocytes, decrease of concentration of IgM (which is high compared to the rates in the control group), and the increase of IgG, combined with increase of TNF−?, IFN−?, IL−2, IL−4 and IL−10. In patients with chronic hepatitis C, the balance of Th1 / Th2 shifts towards subpopulation Th2, that shows a decrease in the level of CD3+, CD4+, CD25+, CD16+ −lymphocytes, IL−2 and IFN−? (cellular immune factors) with activation and hyperproduction CD20+ − lymphocytes, IgM, G and TNF−? and IL−4, IL−10 (humoral immune factors). The immune status of patients with chronic hepatitis C with replicative activity of the pathogen confirmed the detection of HCV−RNA in the blood characterized by decrease of the levels of IFN−?, IL−2, which is accompanied by a significant increase of the TNF− ?, IL−4 and IL−10. It is concluded that specific immune response to antigenic determinants of HCV depends on the form of the disease. The state of immune regulation in patients with HCV infection depends on replicative virus activity, its genotype and biochemical activity of hepatitis C.
Key words: acute hepatitis C, сhronic hepatitis C, immune regulation, сytokines, lymphocyte subpopulation.