%0 Journal Article
%T NGM282: A step forward in the nonalcoholic steatohepatitis treatment landscape?
%A Luca Valenti
%A Valerio Nobili
%J SCIE-indexed Journal
%D 2018
%X Nonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of liver disease worldwide, and the prevalence is still increasing, especially during the developmental age (1-3). NAFLD is defined in the presence of increased hepatic fat content not explained by at risk alcohol intake, and is epidemiologically associated with obesity, insulin resistance and metabolic disorders. It spans a histological spectrum ranging from simple uncomplicated steatosis, to nonalcoholic steatohepatitis (NASH), which is characterized by hepatocellular damage and inflammation and may progress to advanced liver disease and hepatocellular carcinoma. The pathogenesis of NASH is multifactorial, but an important role is likely played by inflammation triggered by predisposing genetic factors, oxidative stress, and bacterial products derived from the gut (4). Recent data seem to suggest that hepatic lipid accumulation itself may also be involved in NASH by inducing lipotoxicity and driving secondary inflammation, leading to activation of fibrogenesis (5,6). Although lifestyle modification, weight loss and increased physical activity are effective in improving liver histology in patients with NASH, these goals are difficult to achieve and maintain. Unfortunately, pharmacological treatments for this condition are not yet available, while they are urgently needed to tackle a possible global rise in liver disease related mortality in the coming years (2). The drugs under development either tackle hepatic fat accumulation, or act downstream by modulating inflammation and fibrogenesis (6). Among drugs that influence hepatic lipid metabolism, particularly promising results have been reported for agonists of Farnesoid X receptor (FXR) such as obeticholic acid, which in a phase 2 trial in patients with NASH was associated with a higher rate of amelioration of hepatic steatosis and fibrosis as compared to placebo (7)
%U http://hbsn.amegroups.com/article/view/22025/21945