Abstract
Without question, nonalcoholic steatohepatitis (NASH) has emerged as a substantial public health problem. The complex and intertwined cellular and molecular mechanisms culminating in the pathophysiology of this disease process remain only partially understood and therapeutic options remain suboptimal. Lipotoxic hepatocyte injury is a cardinal feature of NASH pathogenesis (1, 2), and ballooned hepatocytes are a prominent histopathologic feature of lipotoxic hepatic injury. In fact, the magnitude of ballooned hepatocytes correlates with disease severity (3), and semiquantitation of hepatocyte ballooning is used to calculate the nonalcoholic fatty liver disease activity score, NAS (4). Dr. Diehl and co-workers made a seminal insight when they discovered that ballooned hepatocytes generate sonic hedgehog (Shh), a ligand of the hedgehog signaling pathway, which promotes hepatic fibrogenesis (5, 6). These data provided mechanistic insight into a mechanism contributing to hepatic fibrogenesis in NASH. However, several relevant questions remain. What is the ballooned hepatocyte, and why does it generate sonic hedgehog? Does NASH targeted therapy alter the number of ballooned hepatocytes in NASH? What is the spectrum of sonic hedgehog signaling in NASH? and Is hedgehog signaling inhibition a strategic pharmacologic strategy for NASH?
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
