Nerve growth factor (NGF) expression in correlation with severity of pruritus in cirrhotic patients

Background:Hepatic pruritus is a very common symptom among different chronic liver diseases, particularly in those related to cholestasis. Its prevalence is variable among liver diseases, ranging from 5% in chronic hepatitis C virus infection to 70% in primary biliary cirrhosis. Its etiopathogenesis remains poorly understood.Nerve growth factor (NGF) is a member of neurotrophins. many studies clearly demonstrate their role in pruritus. Nerve growth factor (NGF) is overexpressed in prurigonodularis and its therapeutic administration is pruritogenic. In atopic dermatitis, NGF is released by keratinocytes, mast cells and fibroblasts and plasma levels of NGF are also elevated and correlate with disease activity.This study examines the hypothesis that expression of NGF protein is altered in cirrhotic patients with pruritus. Patients and Methods: To test our hypothesis, we examined the expression patterns of NGF protein in cirrhotic patients with pruritus, cirrhotic patients without pruritus and corresponding healthy (control). skin biopsies (20 specimens each) were evaluated using immunoperoxidase staining techniques. Results: We found variations between the skins of cirrhotic patients with and without pruritus and healthy skin. In healthy skin, the expression of NGF protein was strong (basal cell keratinocytes), moderate (spinouslayer), and weak or abscent (granular cell layer). In contrast, marked expression of NGF protein was observed in all layers of skin (total NGF epidermis and dermis) incirrhotic patients with pruritus in comparison with cirrhotic patients without pruritus and healthy control and this was statistically significant. NGF protein expression was strong (basal cell keratinocytes), moderate (spinous layer), and weak or abscent (granular cell layer). The expression of NGF protein was strong in the adnexal structures. Conclusions: We report, for the first time, increased expression of NGF protein in the epidermal keratinocytes of cirrhotic patients with pruritus skin. Our findings suggest possible roles for this protienin pathophysiology of hepatic pruritus. The clinical ramifications of these observations mandate further investigations.