الفهرس 
Introduction and aim of workOnly 14 pages are availabe for public view
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Abstract
Abstract
Liver diseases constitute a worldwide health problem. HCV infection is one of the commonest liver disorders. A variety of cutaneous symptoms and signs may be the early manifestations of liver impairment. Apoptosis is an essential strategy of dynamic balance in the living system. The aim of the present work is to study the clinical, histopathological and immunohistochemical skin changes in liver disease patients, with special emphasis to those related to skin apoptosis and its markers.The present study was conducted on 105 liver disease patients attending the out-patient clinic of Dermatology, STD’s & Andrology Department and both the out-patient clinic and the in-patient section of Internal Medicine Department, Al-Minya University Hospital.They were subjected to full history taking, general and dermatological examination as well as routine laboratory investigations. Biopsies were obtained from some lesional skin and apparently normal skin of the thigh of 40 advanced HCV infected patients and 5 normal controls. Sections were prepared and stained with H&E, Geimsa and Fontana-Masson stains. Meanwhile, immunohistochemical examination of skin biopsies obtained from 20 advanced HCV infected patients and 5 normal controls were performed. This aims for evaluation of apoptosis regulating markers including; pro-apoptotic (Bax, Fas, P53 and Caspase 3) and anti-apoptotic (Bcl-2 and Bcl-xL) markers as well as detection of apoptotic cells (TUNEL technique) in epidermal keratinocytes. Cutaneous hyperpigmentation was noted in 43 patients (41 %). This could be attributed to marked hyperpigmentation of basal keratinocytes which was more pronounced by the epidermal thinning. Pruritus was demonstrated in 37 patients (35.2 %). This could be attributed to central and/or peripheral causes. Meanwhile, the pruritus in the present study could be also explained by xerosis and pruritic specific skin lesion (e.g. LP and NAE). Moreover, histopathological study of skin biopsies from patients with pruritus revealed an increase in number of mast cells among the mononuclear cell infiltrate which on degranulation pharmacological mediators are released. These mediators play a key role in the production of itching. Meanwhile, LP is observed in 36.19 % of patients with generalized LP in 24 patients, ordinary LP in 12 patients, hypertrophic LP in 1 patient and actinic LP in 1 patient. NAE was present in 4 patients (3.8 %). Histological examination of skin biopsies from NAE of 3 patients showed sheets of necrotic keratinocytes in the upper most portions of spinous cell layer. While, skin biopsy from 1 patient showed psoriasiform epidermal hyperplasia. Advanced liver disease HCV patients are associated with an increase in the expression of skin pro-apoptotic markers (Bax, Fas, P53 and Caspase 3) which could explain the increase of the apoptotic index. Meanwhile, the decreased epidermal thickness could be attributed to increased keratinocyte apoptosis. Whether this alteration in the skin proliferation/ apoptosis balance is attributed to the metabolic and biochemical changes present in liver cell failure or to the direct effect of the virus remains to be clarified. Collaboration of ideas and efforts, in a team work, is mandatory between Hepatologists, Dermatologists, Dermatopathologists and Clinical Pathologists to perform this task.