NASH - Fibrosis

Discover the cutting edge of NAFLD knowledge

NASH (non-alcoholic steatohepatitis), NAFLD (non-alcoholic fatty liver disease), and fibrosis are a set of liver pathologies that have been rising for the past decades and are now on the verge of growing into a global epidemy. They stem from the accumulation of fat in the liver, which is the first and reversible event to occur within the physio-pathological progression from a healthy liver to NASH. This abnormal and significant lipid accumulation in the liver, referred to by the terms hepatic steatosis, Simple Steatosis (SS) or (Non-Alcoholic) Fatty Liver (NAFL), is the result of a dramatic increase of free fatty acid fluxes into the organ. This condition is understood to arise from mis-regulation of portions of the lipid metabolism including lipogenesis, beta-oxidation mechanisms and the whole export/uptake/storage axis.

Progression steps from healthy liver to of NAFLD & NASH related pathologies

Cisbio has developed a panel of ready-to-use assays to monitor biomarkers, phosphoproteins and transcription factors involved in the development and progression of NASH, NAFLD and fibrosis. In addition to our commitment to develop the best possible tools for your research, we also provide guidelines, tips, data and various content on NASH. Guides, Infographics, application notes dedicated to NASH are now at your fingertips!

Non-alcoholic fatty liver

Accumulation of fat in the liver is the first and reversible event that occurs within the physio-pathological progression from a healthy liver to NASH. This abnormal and significant lipid accumulation in the liver, referred to by the terms hepatic steatosis, Simple Steatosis (SS) or (Non-Alcoholic) Fatty Liver (NAFL), is the result of a dramatic increase of free fatty acid fluxes into the organ. This condition is understood to arise from mis-regulation of portions of the lipid metabolism including lipogenesis, beta-oxidation mechanisms and the whole export/uptake/storage axis.

Cisbio has developed a panel of ready-to-use assays to monitor biomarkers, phosphoproteins and transcription factors involved in the steps leading to Hepatic Steatosis.

Hepatic Steatosis is linked to mis-regulations in the metabolsim of fat. Unchecked activation of lipogenesis, beta-oxidation and misdirection in fat storage, uptake and export contribute to fat accumulation in droplets that characterize steatosis. These mis-regulations are often linked to defects in insulin signaling, which regulates the management of lipid droplets lipophagy via mTOR complexes.

Non-alcoholic steatohepatitis

The pathogenic components of NASH are complex and multifactorial. Recent findings have challenged the prior knowledge of that pathology and postulated a pathogenesis involving organ-organ interactions and a multitude of events occurring in parallel. Those include but could be not limited to genetic predisposition, insulin resistance, adipose tissue dysfunction, abnormal lipid metabolism, lipotoxicity, altered production of inflammatory mediators, and dysregulation of the gut-liver axis and innate immunity.

Cisbio offers a wide range of high-quality assays to monitor those multifactorial processes from inflammatory, immunity, lipotoxicity and cell signaling standpoints.

Kupffer cells activation is mainly related to their surface TLR4 and cytosolic TLR9 signaling following the capture of bacterial PAMPs. The ensuing signal transduction promotes a pro-inflammatory environment in which hepatocyte damages are more likely to occur
Hepatocyte damages and inflammation in NASH are promoted via two main axis. Firstly, the accumulation of fat leads to an increased production of mitochondrial ROS to perform beta-oxidation, as well as an increase in lipotoxic metabolites, all of which create cytosolic stress. Secondly, pro-inflammatory mediators promote inflammation and cell death of hepatocyte via interleukin signaling, TNF-alpha and TGF-beta receptors.

Liver fibrosis

Hepatic fibrosis that happens with NASH is a healing response to chronic liver injury and inflammation. It is characterized by the excessive deposition of extracellular matrix (ECM) as the result of an imbalance between ECM synthesis and degeneration. When damaged by NASH, hepatocytes express inflammatory mediators that call and activate immune cells to the site. The lasting inflammation signal that result from that call forces quiescent hematopoietic stem cells (HSCs) differentiation into myofibroblasts which then drive liver fibrosis with ECM secretion.

Cisbio has developed a panel of high-quality assays to read those pro-inflammatory steps as well as the differentiation mechanisms of HSCs and the subsequent activity of newly formed myofibroblasts.

HSC differentiation into myofibroblast is a hallmark of liver fibrosis and results from a wide range extra-cellular signals. These include but are not limited to TGF-beta signaling, inflammatory cytokines, TLR activation and the PDGF pathway.
Myofibroblast activation is the liver’s attempt to heal from hepatocyte inflammation and death. Myofibroblasts migrate to inflammed zones and secrete high amounts of extracellular matrix components. Chronic NASH-related injury promotes this mechanism through TGF-beta signaling and the Hippo pathway.