الفهرس 
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Abstract
Pruritus is a common symptom in hepatobiliary disorders. Its prevalence is variable among liver diseases, ranging from 5% in chronic hepatitis C virus infection to 70% in primary biliary cirrhosis. It remains unclear how peripheral and central mechanisms of pruritus takes place. Pruritic skin diseases are associated with increased production and release of cytokines, neuropeptides and neurotrophins which possibly leading to the exacerbation of pruritus.
The objective of this study was to explore the expression pattern of NGF and its receptor TrKA in cirrhotic patients with pruritus in comparison to cirrhotic patients without pruritus and control groups (healthy volunteers) and to evaluate correlations between the tissue levels of the measured parameters and severity of the pruritus. The study included 40 patients (20 were cirrhotic with pruritus and 20 were cirrhotic without pruritus) as well as 20 age and sex matched healthy volunteers who attended the outpatient clinic of Dermatology, Venereology and Andrology Department or Department of Gastroenterology and Tropical Medicine Sohag University Hospital between January 2015 to December 2016. Punch skin biopsies (4 mm) each were obtained from all participants and were processed for routine histology (Hematoxylin and eosin stains) and special (Giemsa stain) as well as immunohistochemical stains at the Department of Pathology, Faculty of Medicine, Assuit University Hospitals.
In the present study the ages of cirrhotic patients with pruritus ranged (35-67) with mean ± SD (52±9.1), the majority of cirrhotic patients with pruritus were from rural areas and in half of the cirrhotic patients with pruritus, the underlying cause of cirrhosis was HCV infection. The results of present study revealed that, liver cirrhosis was classified according to Child Pugh classification and half of the patients were class A.
In this study , assessment of severity of pruritus in cirrhotic patients was done using 5- D itch score and the mean ±SD 5-D score obtained in the study group was 15.3± 4.9 with scores ranging between 6 and 25. sleep is the most affected aspect in the disability domain with mean ±SD (3.1± 0.9). The current study demonstrated several histological changes in the skin of cirrhotic patients with pruritus including: epidermal hyperplasia, vascular ectasia, hypertrophied dermal nerve endings, mixed inflammatory cellular infilterate and lymphocytic vasculopathy. We found also increased numbers of mast cells which have perivascular, perineural and interstitial distribution.
In the current study, The expression pattern of NGF and its receptor TrkA protein in the skin of cirrhotic patients with pruritus were higher in both the epidermis and dermal adnexal structures in comparison to cirrhotic patients without pruritus and normal healthy skins. We found a positive correlation between the expression of NGF and its receptor TrkA and severity of pruritus in cirrhotic patients. This study also demonstrated that there was a relation between severity of pruritus and HCV as a cause of liver cirrhosis.
In conclusion, this study highlights for the first time the expression of NGF and its receptor TrkA in the skin of cirrhotic patients with pruritus. Based on the results of this study, it is suggested that these proteins (NGF/TrkA) have a pathophysiological role of in the mechanism of pruritus in cirrhotic patients. So, It is speculated that as proper understanding of interactions between the cutaneous neurosensory system and various components of skin and immune system in health and disease will open a window for future vehicle for not only a pruritus associated with hepatic disorders but also in itchy skin dermatoses such as prurigo nodularis, atopic dermatitis and lichen planus.
Recommendations
1- Further studies should be done to evaluate the expression pattern of NGF and its receptor TrkA in other systemic diseases associated with pruritus.
2- Try to clarify the possibility of using anti- NGF and/or anti- TrkA antibodies as a new line of treatment not only for hepatic pruritus, but also for other itchy skin dermatoses such as prurigo nodularis, atopic dermatitis and lichen planus.