Nonalcoholic steatohepatitis and insulin resistance: interface between gastroenterologists and endocrinologists

Nonalcoholic steatohepatitis (NASH), along with other forms of nonalcoholic fatty liver disease, is an increasingly common clinico-pathological syndrome. It is frequently associated with obesity, especially visceral fat, and type 2 diabetes, and is intimately related to markers of the insulin resistance syndrome. Both the prevalence and the severity of liver steatosis are related to body mass index, waist circumference, hyperinsulinaemia, hypertriglyceridemia and impaired glucose tolerance. The pathophysiology of NASH involves two steps: 1) insulin resistance, which causes steatosis; 2) and oxidative stress, which produces lipid peroxidation and activates inflammatory cytokines. The identification of subjects who may progress from fatty liver to NASH, and from NASH to fibrosis/cirrhosis is an important clinical challenge as well as the finding of appropriate therapy that could prevent such deleterious process. Substantial weight loss is accompanied by a marked attenuation of insulin resistance and related metabolic syndrome and, concomitantly, by an important regression of liver steatosis in most patients, although mild inflammation may be detected in some subjects. Thus, NASH may be considered as another disease of affluence, as is the insulin resistance syndrome and perhaps being part of it.