'Endocrine NAFLD' a hormonocentric perspective of nonalcoholic fatty liver disease pathogenesis

In 1980, Ludwig named nonalcoholic steatohepatitis (NASH) what we now consider to be one of the manifestations of the broader nonalcoholic fatty liver disease (NAFLD) spectrum. He described 20 patients whose liver biopsy specimens were characterized by striking fatty and necroinflammatory changes, Mallory bodies, fibrosis and cirrhosis. The disease was more common in women, most patients were moderately obese, and many had diabetes mellitus, gallstones and thyroid disease [1].A quarter of a century later, we know that the pathogenesis of NAFLD is complex and multifactorial. Clues to its comprehension, however, were probably suggested by features highlighted in Ludwig's series: insulin resistance (IR) (obesity, diabetes and gallstones), fatty-inflammatory liver changes [now considered components of the metabolic syndrome (MS)] and involvement of the endocrine system (diabetes, thyroid dysfunction and prevalence of the female gender).The link between IR, sub-clinical inflammation, MS and NAFLD is now widely accepted [2], [3], [4] and [5] but a core unifying explanation for the MS is lacking. Starting from the hypothesis that many hormones and cytokines function in metabolic and immune roles and, in doing so, they control inflammation [6], [7] and [8] we systematically looked for hormonal derangements associated with NAFLD