Hepatic Microcirculation in Fatty Liver Disease
Article first published online: 16 MAY 2008
Copyright © 2008 Wiley-Liss, Inc.
The Anatomical Record
Volume 291, Issue 6, pages 684–692, June 2008
How to Cite
Farrell, G. C., Teoh, N.C. and Mccuskey, R.S. (2008), Hepatic Microcirculation in Fatty Liver Disease. Anat Rec, 291: 684–692. doi: 10.1002/ar.20715
- Issue published online: 16 MAY 2008
- Article first published online: 16 MAY 2008
- Manuscript Accepted: 19 DEC 2007
- Manuscript Received: 25 MAY 2007
- fatty liver;
- liver transplantation
Nonalcoholic fatty liver disease (NAFLD), the most common cause of steatosis, is associated with visceral obesity and insulin resistance. With more severe risk factors (obesity, type 2 diabetes [T2D], metabolic syndrome), steatosis may be complicated by hepatocellular injury and liver inflammation (steatohepatitis or NASH). NASH can lead to perisinusoidal fibrosis and cirrhosis. Fat-laden hepatocytes are swollen, and in steatohepatitis, further swelling occurs due to hydropic change (ballooning) of hepatocytes to cause sinusoidal distortion, as visualized by in vivo microscopy, reducing intrasinusoidal volume and microvascular blood flow. Involvement of other cell types (sinusoidal endothelial cells, Kupffer cells, stellate cells) and recruitment of inflammatory cells and platelets lead to dysregulation of microvascular blood flow. In animal models, the net effect of such changes is a marked reduction of sinusoidal space (∼50% of control), and a decrease in the number of normally perfused sinusoids. Such microvascular damage could accentuate further liver injury and disease progression in NASH. The fatty liver is also exquisitely sensitive to ischemia-reperfusion injury, at least partly due to the propensity of unsaturated fatty acids to undergo lipid peroxidation in the face of reactive oxygen species (ROS). This has important clinical consequences, particularly limiting the use of fatty donor livers for transplantation. In this review, we discuss available data about the effects of steatosis and steatohepatitis on the hepatic microvascular structure and sinusoidal blood flow, highlighting areas for future investigation. Anat Rec, 291:684–692, 2008. © 2008 Wiley-Liss, Inc.