Fig. 1

Hepatic sinusoid in normal and cirrhotic livers. In (a), a schematic sinusoid representation from a normal liver. Hepatocytes exchange digestive end products, toxins, and metabolites with the sinusoidal blood. This vascular structure, which is lined by fenestrated endothelial cells (LSEC), drains blood from the portal triad to the central vein. The characteristic fenestrae of the LSECs contribute to the rapid transport of solutes across the subendothelial space. Kupffer cells are found in the sinusoid while hepatic stellate cells are located in the subendothelial space, named the space of Disse. Hepatic stellate cells (HSCs) store retinoids within perinuclear lipid droplets. In (b), as fibrosis develops, changes occur within the subendothelial space and within the hepatic sinusoid. These changes include alterations in both cellular morphology and extracellular matrix composition. Activated HSCs lose their retinoid reserve and become the primary source of extracellular matrix. They may also participate in sinusoidal contraction. In addition, there is a loss of hepatocyte microvilli and endothelial fenestrae. Transport across the sinusoidal wall is hence reduced, leading to deterioration of hepatic function. Activation of Kupffer cells accompanies liver injury and contributes to HSC activation