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Nonalcoholic fatty liver disease (NAFLD) advanced to cirrhosis is often complicated by clinically significant portal hypertension, which is primarily caused by increased intrahepatic vascular resistance. Liver fibrosis has been identified as a critical determinant of this process. However, there is evidence that portal venous pressure may begin to rise in the earliest stages of NAFLD when fibrosis is far less advanced or absent. The biological and clinical significance of these early changes in sinusoidal homeostasis remains unclear. Experimental and human observations indicate that sinusoidal space restriction due to hepatocellular lipid accumulation and ballooning may impair sinusoidal flow and generate shear stress, increasingly disrupting sinusoidal microcirculation. Sinusoidal endothelial cells, hepatic stellate cells, and Kupffer cells are key partners of hepatocytes affected by NAFLD in promoting endothelial dysfunction through enhanced contractility, capillarization, adhesion and entrapment of blood cells, extracellular matrix deposition, and neovascularization. These biomechanical and rheological changes are aggravated by a dysfunctional gut–liver axis and splanchnic vasoregulation, culminating in fibrosis and clinically significant portal hypertension. We may speculate that increased portal venous pressure is an essential element of the pathogenesis across the entire spectrum of NAFLD. Improved methods of noninvasive portal venous pressure monitoring will hopefully give new insights into the pathobiology of NAFLD and help efforts to identify patients at increased risk for adverse outcomes. In addition, novel drug candidates targeting reversible components of aberrant sinusoidal circulation may prevent progression in NAFLD.

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Autor(es)

Baffy, Gyorgy - 

Id.: 70979251

Idioma: inglés (Estados Unidos)  - 

Versión: 1.0

Estado: Final

Palabras claveIntrahepatic vascular resistance - 

Tipo de recurso: Journal Article  - 

Tipo de Interactividad: Expositivo

Nivel de Interactividad: muy bajo

Audiencia: Estudiante  -  Profesor  -  Autor  - 

Estructura: Atomic

Coste: no

Copyright: sí

: open

Requerimientos técnicos:  Browser: Any - 

Relación: [References] 10.1007/s10620-017-4903-5
[References] Digestive Diseases and Sciences

Fecha de contribución: 10-feb-2018

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Localización:
* Quick submit: 2018-01-24T09:27:27-0500
* Baffy, Gyorgy. 2018. “Origins of Portal Hypertension in Nonalcoholic Fatty Liver Disease.” Digestive Diseases and Sciences (January 22). doi:10.1007/s10620-017-4903-5.
* 0163-2116

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