Hepatic Microcirculation in Fatty Liver Disease

Date

2008

Authors

Farrell, Geoffrey
Teoh, Narcissus
McCuskey, Robert

Journal Title

Journal ISSN

Volume Title

Publisher

John Wiley & Sons Inc

Abstract

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.

Description

Keywords

Keywords: animal; disease model; donor; fatty liver; hepatitis; human; insulin resistance; lipid peroxidation; liver circulation; liver transplantation; macrophage; microcirculation; mouse; pathology; pathophysiology; physiology; rat; review; Animals; Disease Model Fatty liver; Liver transplantation; Microcirculation; Steatosis

Citation

Source

The Anatomical Record

Type

Journal article

Book Title

Entity type

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Restricted until

2037-12-31