Hepatitis B Virus (HBV)

Liver fibrosis and altered matrix synthesis: MECHANISMS OF ACUTE AND CHRONIC LIVER INJURY Part 1

Inflammation: Inflammatory processes are characterized by migration of inflammatory cells into areas affected by various noxious agents. Migration induced by chemokines released at sites of injury is mediated by the interaction of adhesion molecules on migrating inflammatory cells and adhesion molecules on resident cells (mostly endothelial cells first and hepatic stellate cells [HSCs] afterwards). Because noxious agents may only induce a ‘disturbance’ of hepatocytes and not necessarily induce cell death, hepatocellular necrosis may be a result of the interaction of ‘disturbed’ hepatocytes with recruited inflammatory cells (Figure 1).

Following hepatocellular necrosis, there is an activation of repair mechanisms that either lead to a restitution ad integrum or, in the case of progressive disease, to the replacement of functional parenchyma by matrix (fibro-genesis). In different animal models of acute liver injury, it has been shown that the accumulation of inflammatory cells and the hepatic necrosis precede the proliferation and activation of HSCs as well as the formation of a ‘provisional clot’, which, therefore, are considered to constitute a part of the expected healing response to hepatocyte necrosis. On the other hand, HSCs may also be capable of contributing to the recruitment of inflammatory cells because it has been demonstrated that HSCs express chemokines. Furthermore, HSCs may be important for the transmigration of inflammatory cells by the synthesis of adhesion molecules as intercellular cell adhesion molecule-l, vascular cell adhesion molecules and neural cell adhesion molecules under conditions of inflammation. Nevertheless, it is not definitively clear whether necroinflammation is always needed for the development of liver fibrosis. In fact, cirrhosis may develop in patients with hemochromatosis without inflammation. However, in most cases, following the persistence of noxious agents, necrosis and inflammation, changes occur that include the so called ‘capillariza-tion’ of the sinusoids, the progressive deposition of ECM and the reduced matrix degradation, which finally leads to a scar formation. You can start online shopping right now – buy levaquin online for more advantages.

Pathogenesis of liver fibrogenesis

Figure 1) Pathogenesis of liver fibrogenesis. Recruitment of inflammatory cells induced by stressed hepatocyctes followed by hepatocellular death. ICAM-I Intercellular adhesion molecule-1; NCAM Neural cell adhesion molecule; VCAM-1 Vascular cell adhesion molecule-1

Category: Gastroenterology

Tags: Liver fibrosis, Matrix

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