ABSTRACT
Chronic, chemical, metabolic, virological or immimological injury leads to hepatocyte necrosis, causing sustained inflammation, as well as cytokinemediated activation and transformation of fat-storing Ito cells.1 These cells subsequently act as a major source of liver fibrogenesis.2 Sinusoidal basement membrane thickening is an early change in the microvasculature, followed by collagen deposition in the space of Disse and, later, fibrosis in and around the portal tracts.3 The sinusoidal spaces are narrowed, and despite a relative increase of spontaneous intrahepatic shunting, portal venous resistance increases, whilst the remaining hepatocyte mass becomes more and more removed from direct splanchnic circulatory access. There is upregulation of intrahepatic vasomotor tone, although the exact role of endothelins, nitric oxide and their receptors remains to be determined.4 Regenerative nodules also contribute to the architectural distortion resulting from liver fibrosis. The principal impact of these changes is a reduction in the capacity of all hepatic synthetic, metabolic and detoxifying functions. Most noticeable amongst many are the nutritional and neurological effects, particularly hepatic encephalopathy, which is more likely at times of increased demand on the liver.
