الفهرس | Only 14 pages are availabe for public view |
Abstract Pruritus is a common dermatologic manifestation that is recognized as an early sign of chronic HCV infection, particularly infections associated with the development of cholestasis. HCV related pruritus could be triggered via direct and indirect mechanisms. Direct mechanism was a consequence of viral overload that initiate the production of several inflammatory mediators such as interleukin-8 (IL-8), chemokine C-C motif ligand 2 (CCL2), chemokine C-X-C motif ligand 1(CXCL1) and CXCL5. On the other hand, HCV related cholestasis is considered as indirect trigger of pruritus via the production of several substances with pruritogenic effect as bile salts, histamine and endogenous opioids. Furthermore, the accumulated autotaxin and its related product lysophosphatidic acid in HCV patients with cholestasis can stimulate nerve ending in epidermis initiating pruritus. Lipocalin-2 (LCN2), also known as neutrophil gelatinase associated lipocalin (NGAL), is a protein secreted mainly by activated neutrophils. It has been recognized as a critical player in different physiological and pathological processes, including iron homeostasis, inflammation, microbial infection, organogenesis, neurodegeneration, and tumorigenesis. Regarding liver diseases, it is found that the expression level of LCN2 was increased and correlated with the degree of hepatic damage, suggesting that LCN2 is as an early biomarker of liver inflammation. In HCV patients, urine LCN2 levels were correlated with degree of hepatic fibrosis. Summary 75 Few studies showed an association between LCN2 level and itching. One of them was experimental a mouse model of atopic dermatitis, while others were done on patients with psoriasis, suggesting that serum LCN2 may be a useful clinical marker for itch. As pruritus in HCV patients has not been explained clearly till now, and the relationship between LCN2 and pruritus in those patients has not been determined; This study examined the role of LCN2 in HCV pruritic patients. This is a case-control study was carried out on 50 subjects that were divided into 2 main groups: 25 HCV patients with pruritus as patient’s group and 25 age and gender matched healthy volunteers as a control group. Cases were selected from the inpatient and outpatient clinics of Internal Medicine department, faculty of Medicine, Menoufia University. While the control subjects were collected from Plastic Surgery department, Menoufia University hospitals. A written informed consent form approved by Committee of Human Rights in Research in our University was obtained from every participant before the study initiation. All patients were free from dermatological diseases and other systemic diseases causing pruritus. Every participant in this study was subjected to both blood sampling and skin biopsy taking in the same session, then each sample was processed separately and blindly at the Biochemistry and molecular biology and Pathology departments as for measuring LCN2 serum levels by enzyme linked immunosorbent assay (ELISA) and Immunohistochemical (IHC) staining of skin biopsies respectively. In the current study, Serum LCN2 was significantly higher in cases than controls respectively (P <0.001). There was a significant relation between serum LCN2 with itching severity and duration. Cases Summary 76 exhibiting severe itching and longer duration had higher level of serum lipocalin-2 (P<0.001, P=0.006 respectively). Regarding immunohistochemistry, There was a significant difference between cases and controls regarding both LCN2 percentage of expression and H scores in epidermis (P <0.001). Furthermore, the percentage of expression of LCN2 in dermal adnexa was significantly higher in cases in relation to controls (P <0.001). |