الفهرس 
IntroductionOnly 14 pages are availabe for public view
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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.
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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
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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).