Endotoxinemia in antiviral therapy for chronic hepatitis c and its potential pharmacologic corrections

159 Chronic hepatitis C (CHC) is a serious medical and social issue. This ailment is associated with a high morbidity rate, possible hepatic cirrhosis and hepatocellular carcinoma [8, 21]. The gold standard in treating chronic hepatitis C is combined antiviral therapy (AVT) with pegylated interferon-alpha (PEG-IFNα) in combination with Ribavirin. At the same time, AVT produces numerous adverse events (AE) that pose considerable difficulties both to the doctor and to the patient. Haematologic disturbances of various intensity manifested as anemia, neutropenia, and thrombocytopenia, are among the leading AE coming along with antiviral therapy [10, 14]. Of this side effect, neutropenia has been studied in fewer details, especially when it comes to the clinical relevance of its negative implications. In case of PEG-IFNα treatment the likelihood of developing neutropenia is 17–34 %, which is higher than in case of short-acting IFNα administration. This could be related to a longer effect PEG-IFNα has on the bone marrow [6, 7, 12]. IFNα causes neutropenia due to both direct myelotoxicity and induced autoimmune response [15]. A consequence of neutropenia developing in patients undergoing AVT could be increased serum levels of endotoxin. In 1952, O. Westphal and O. Luderitz succeeded in decoding the biochemical formula of endotoxin and set the terms endotoxin and lipopolyssacharide (LPS) equal [18]. The dominant cellular acceptors for LPS in blood are polymorphonuclear leukocytes, macrophages, and platelets. Human granulocytes are an important endotoxin-binding system involved in complex processes connected to immobilization, transport and removing LPS from the body. Endotoxin binding with granulocytes and macrophages induces, on the one hand, the development of protective mechanisms network, while on the other – production of cytokines and cytokine mediated destruction of various organs and tissues [2, 19]. Therefore, increased levels of endotoxin against the developing neutropenia may suppress significantly the protective capacity of the immune system. However the clinical significance of endotoxinemia elevated indicators in case of AVT has not been detected yet, nor have its potential negative effects. The purpose of the study is to investigate the serum levels of endotoxin against neutropenia in patients with CHC who undergo antiviral therapy, as well as detecting pharmacologic corrections for endotoxinemia. Material and Methods. The course of neutropenia through AVT was investigated in 101 patients diagnosed with chronic hepatitis C – 38 females and 63 males. The age varied from 18 to 62 (37.6±0.7 yrs). 62 of the patients (61.4 %) had HCV genotype 1 infection while others revealed non-1 (HCV genotypes 2 and 3). The average level of viremia was 4.9±1.2 log10. None of the patients was diagnosed with any hepatic cirrhosis stage. In all the patients the combined AVT was administered with IFN-α and Ribavirin. Of them 83 patients were given PEG-IFN-α-2a (Pegasys), while another 18 – short-acting IFN-α. The duration of the therapy depended on the HCV genotype – 24 weeks in case of HCV genotypes 2 and 3, and 48 weeks in case of HCV genotype 1. The serum levels of endotoxin were detected with chromogenic assay (Hbt LAL Hycult Вiotech, Netherlands). The control group included 20 healthy volunteers aged 21–42 yrs. The results obtained were processed using Microsoft Excel, Biostat, and STATISTICA 6.0. The comparative analysis of the parameters in groups with normal distribution was done using Student’s t-test; for groups with non-normal distribution – Mann-Whitney test. Spearman’s rank correlation coefficient was employed to reveal the correlation dependence. Results and Discussion. The total number of leukocytes and the number of neutrophils prior to the antiviral therapy were within the normal ranges. There is data saying that patients with hepatitis C initially have a lower count of neutrophils if compared to the control group [5]. At the same time the level of neutrophils below 2900 cells/mcl at the start of © Group of authors, 2014 UDC 616.36-002:616.155. 14 DOI – http://dx.doi. org/10.14300/mnnc.2014. 09045 ISSN – 2073-8137