Pathogenesis of hepatic steatosis: The link between hypercortisolism and non-alcoholic fatty liver disease

Abstract

Based on the available literature, non alcoholic fatty liver disease or generally speaking, hepatic steatosis, is more frequent among people with diabetes and obesity, and is almost universally present amongst morbidly obese diabetic patients. Non alcoholic fatty liver disease is being increasingly recognized as a common liver condition in the developed world, with non alcoholic steatohepatitis projected to be the leading cause of liver transplantation. Previous data report that only 20% of patients with Cushing’s syndrome have hepatic steatosis. Aiming at clarifying the reasons whereby patients suffering from Cushing’s syndrome - a condition characterized by profound metabolic changes - present low prevalence of hepatic steatosis, the Authors reviewed the current concepts on the link between hypercortisolism and obesity/metabolic syndrome. They hypothesize that this low prevalence of fat accumulation in the liver of patients with Cushing’s syndrome could result from the inhibition of the so-called low-grade chronic-inflammation, mainly mediated by Interleukin 6, due to an excess of cortisol, a hormone characterized by an anti-inflammatory effect. The Cushing’s syndrome, speculatively considered as an in vivo model of the hepatic steatosis, could also help clarify the mechanisms of non alcoholic fatty liver disease.

Keywords: Nonalcoholic fatty liver disease, Cushing’s syndrome, Hypercotisolism

Core tip: This overview of the literature is related to hepatic steatosis, its prevalence, clinical consequences and, in particular, the pathogenesis of this disorder. The authors focus on the link between hypercortisolism and obesity/metabolic syndrome. The main question of the work relates to the low prevalence of hepatic steatosis (only 20%) described in 50 newly diagnosed patients with Cushing’s syndrome based on appropriate computed tomography scans available for retrospective analysis. The authors try to explain this finding by the anti-inflammatory effect of high circulating levels of glucocorticoids.