Liver cirrhosis and hepatic stellate cells

Abstract

The cirrhosis represents the final stage of several chronic hepatic diseases and it is characterized by the presence of fibrosis and morphologic conversion from the normal hepatic architecture into structurally abnormal nodules. In the evolution of the disease there is loss of the normal vascular relationship and portal hypertension. There are also regenerative hepatocelular alterations that become more prominent with the progression of the disease. The liver transplantation continues to be the only therapeutic option in cases of disease in terminal phase. The hepatic stellate cells (HSC) are perisinusoidal cells that store vitamin A and produce growth factors, citocins, prostaglandins and other bioactive substances. They can suffer an activation process that convert them to cells with a phenotype similar to myofibroblasts. When activated, they present increased capacity of proliferation, mobility, contractility and synthesis of collagen and other components of extracelular matrix. They possess cytoplasmic processes adhered to sinusoids and can affect the sinusoidal blood flow. HSC are important in pathogenesis of fibrosis and portal hypertension. Key words: Liver. Stellate Cells. Hepatic Fibrosis. Hepatic Cirrhosis. Perisinusoidal Cells. Portal Hypertension. RESUMOA cirrose representa o estágio final de diversas doenças hepáticas crônicas e é caracterizada pela presença de fibrose e conversão da arquitetura hepática normal em nódulos estruturalmente anormais. Na evolução da doença ocorre perda da relação vascular normal e hipertensão portal. Há também alterações regenerativas hepatocelulares que se tornam mais proeminentes com a progressão da doença. O transplante hepático permanece como a única opção terapêutica nos casos de doença em fase terminal. As células estreladas hepáticas (CEH) são células perisinusoidais que armazenam vitamina A e produzem fatores de crescimento, citocinas, prostaglandinas e outras substâncias bioativas. Podem sofrer um processo de ativação para um fenótipo semelhante a miofibroblastos. Quando ativadas apresentam maior capacidade de proliferação, motilidade, contractilidade, síntese de colágeno e componentes da matriz extracelular. Possuem processos citoplasmáticos aderidos aos sinusóides e podem afetar o fluxo sangüíneo sinusoidal. As CEH são importantes na patogênese da fibrose e hipertensão portal. Descritores: Fígado. Células Estreladas. Fibrose Hepática. Cirrose Hepática. Células Peri-sinusoidais. Hipertensão Portal.

MR Imaging of activated hepatic stellate cells in liver injured by CCl4 of rats with integrin-targeted ultrasmall superparamagnetic iron oxide

“…Liver fibrosis is a wound-healing process presenting in the chronically injured liver regardless of underlying etiologies and is characterized by excessive deposition and failure to degrade the extracellular matrix (ECM) [1][2][3][4]. Upon the initiation of liver injury, the hepatic stellate cells (HSCs) transit from quiescent to activated phenotype referred to the transdifferentiated myofibroblast-like cells, which are responsible for overproduction of ECM materials and subsequent formation of the fibrous septa in damaged liver [2,5].…”

“…Upon the initiation of liver injury, the hepatic stellate cells (HSCs) transit from quiescent to activated phenotype referred to the transdifferentiated myofibroblast-like cells, which are responsible for overproduction of ECM materials and subsequent formation of the fibrous septa in damaged liver [2,5]. Therefore, HSCs play a crucial role in the development of liver fibrosis.…”

Gallic Acid and Dodecyl Gallate Prevents Carbon Tetrachloride-Induced Acute and Chronic Hepatotoxicity by Enhancing Hepatic Antioxidant Status and Increasing p53 Expression

“…6,19,33) Damages to the parenchymal and non-parenchymal liver cells result in elevations of the both ALT, AST and GGT, which have been widely accepted as major biomarkers to assess the hepatic injury. 2,34,35) The increase in serum level of these markers indicates a loss of liver cell membrane integrity, which might be directly related to an increase in ROS CCl 4 -induced. 36,37) In our study, we observed an obvious increase in the levels of TG about 63 and 113% in acute and chronic model respectively and TC about 38% in chronic model, which is in accordance with previous reports.…”

Hepatitis B virus X protein activates human hepatic stellate cells through upregulating TGFβ1

“…When HSCs are activated, they show an increased capacity for proliferation, mobility, contractility, and synthesis of collagen and other components of the extracellular matrix (ECM) (Pinzani et al., 1998;Pinzani and Marra, 2001;Brandão et al, 2006). Excessive deposition of ECM is a characteristic of fibrogenesis, which effectively amplifies the fibrogenic response (Hui and Friedman, 2003;Parsons et al, 2007).…”

“…In addition, expression of α-SMA is also a significant sign of HSC activation (Brandão et al, 2006). Excessive synthesis of ECM components leads to increased expression of α-SMA as well as changes in the expression of L-type voltage-operated Ca 2+ channels, which are known to mediate Ca 2+ influx and regulate cellular contraction (Gasull et al, 2001;Ahmad and Ahmad, 2012).…”