The pathogenesis of NASH is being unravelled by studies of animal models and humans with this disorder. The necro-inflammatory component of NASH appears to be modulated by interactions among various factors (for example, cytokines, hormones, neurotransmitters) that regulate the biological activity of TNF-α and other proinflammatory (Th-1) cytokines. Hepatic necroinflammation is necessary, but not sufficient, for progression to cirrhosis. Factors such as leptin and certain leptin inducible factors (for example, noradrenaline), that regulate the activity of profibrogenic cytokines, such as IL-10 and TGF-β, dictate the extent of fibrosis that occurs during liver injury. A better understanding of how these and other soluble and cell associated factors regulate the phenotypes of different types of liver cells should help us to develop rationale treatments for NASH and other disorders in the dysmetabolic syndrome.
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