Specialized Proresolving Mediators: Enhancing Nonalcoholic Steatohepatitis and Fibrosis Resolution

The resolution of necroinflammation and fibrosis remains a primary clinical target in nonalcoholic steatohepatitis (NASH), the most common chronic liver disease and a major cause of end-stage liver disease. Our understanding of the basic molecular mechanisms driving inflammation and fibrosis and their resolution in obesity-related conditions, including NASH, have led to the proposal of a novel, tractable therapeutic paradigm involving specialized proresolving mediators (SPMs), namely lipoxins (LXs), resolvins (Rvs), protectins (PDs), and maresins (MaRs). Growing evidence from cellular and in vivo animal models, as well as observational human data, suggests that the therapeutic potential of SPMs and their synthetic mimetics expands to the regression of hepatic necroinflammatory and fibrotic changes in NASH. Here, we review preclinical and clinical evidence linking SPMs to the pathogenesis of inflammation and fibrosis in NASH, as well as potential therapeutic use of these new molecules for the resolution of steatohepatitis and of fibrosis in NASH.