Zonal Extracellular Matrix (ECM) Accumulation in Nonalcoholic Steatohepatitis (NASH) Characterized by a Mathematical Model of Fibrosis
Non-alcoholic fatty liver disease (NAFLD) is of growing concern, within developed countries, with recent estimates suggesting up to, 30% of the US population may be affected. NAFLD represents a, spectrum of pathophysiology, ranging from hepatic steatosis,, through non-alcoholic steatohepatitis (NASH) and hepatic fibrosis,, and in rare cases resulting in cirrhosis and liver failure. Hepatic, fibrosis in NASH is caused by excessive accumulation of, extracellular matrix (ECM) proteins. Fibrosis progresses over time due to an increased number of activated hepatic stellate cells (HSCs) and subsequently increased production of hepatic ECM proteins. Fibrosis in NASH is histologically described by the accumulation of ECM in different hepatic acinar zones, with stage I fibrosis occurring in zone 3, stage II fibrosis expanding to zone 1, and stage III fibrosis bridging zones 1 and 3. This zonal pattern of ECM accumulation has not been captured in mathematical models of NASH fibrosis to date.
Ninth American Conference on Pharmacometrics (ACoP) Annual Meeting, October 6-12, 2018, San Diego, CA
By Grant T. Generaux, Diane M. Longo, Paul B Watkins, Brett A Howell, and Scott Q Siler