Hepatic stellate cell activation and liver fibrosis are associated with necroinflammatory injury and Thl‐like response in chronic hepatitis C

Svegliati‐Baroni, Gianluca; Pastorelli, Alfredo; Manzin, Aldo; Benedetti, Antonio; Marucci, Luca; Solforosi, Laura; Sario, A. Di; Brunelli, E.; Orlandi, F.; Clementi, Massimo; Macarri, Giampiero

doi:10.1111/j.1478-3231.1999.tb00038.x

Cited by 78 publications

(46 citation statements)

References 49 publications

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“…Nowadays, it is well established that the host immune response, which is regulated by the host genetic background, plays a prominent role in the natural history of the disease [3,8,52]. A positive correlation between a high level of pro-inflammatory cytokines secreted in response to HCV-related liver injury, and an increased necroinflammatory activity, liver fibrosis or cirrhosis was previously reported [8,10,11,53]. Cytokine production varies among individuals and is associated with certain mutations within the coding and the regulatory regions [27].…”

Section: Discussionmentioning

confidence: 89%

Combined effect of pro- and anti-inflammatory cytokine gene polymorphisms on susceptibility to liver cirrhosis in Tunisian HCV-infected patients

et al. 2011

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Section: Discussionmentioning

confidence: 89%

Combined effect of pro- and anti-inflammatory cytokine gene polymorphisms on susceptibility to liver cirrhosis in Tunisian HCV-infected patients

et al. 2011

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“…[20][21][22][23] Several semiquantitative scoring systems (e.g., Ishak and METAVIR fibrosis score) have been described. [24][25][26][27] All are time consuming and produce partially subjective fibrosis evaluations that are not very precise. 23 It has been shown that computerized imaging enables a precise quantification of fibrosis, and we have used this technique in a recent investigation of the effects of liver disease on cationic drug pharmacokinetics.…”

Section: Discussionmentioning

confidence: 99%

Quantitative evaluation of altered hepatic spaces and membrane transport in fibrotic rat liver

et al. 2002

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Four animal models were used to quantitatively evaluate hepatic alterations in this study: (1) a carbon tetrachloride control group (phenobarbital treatment only), (2) a CCl 4 -treated group (phenobarbital with CCl 4 treatment), (3) an alcohol-treated group (liquid diet with alcohol treatment), and (4) a pair-fed alcohol control group (liquid diet only). At the end of induction, single-pass perfused livers were used to conduct multiple indicator dilution (MID) studies. Hepatic spaces (vascular space, extravascular albumin space, extravascular sucrose space, and cellular distribution volume) and water hepatocyte permeability/surface area product were estimated from nonlinear regression of outflow concentration versus time profile data. The hepatic extraction ratio of 3 H-taurocholate was determined by the nonparametric moments method. Livers were then dissected for histopathologic analyses (e.g., fibrosis index, number of fenestrae). In these 4 models, CCl 4 -treated rats were found to have the smallest vascular space, extravascular albumin space, 3 H-taurocholate extraction, and water hepatocyte permeability/surface area product but the largest extravascular sucrose space and cellular distribution volume. In addition, a linear relationship was found to exist between histopathologic analyses (fibrosis index or number of fenestrae) and hepatic spaces. The hepatic extraction ratio of 3 H-taurocholate and water hepatocyte permeability/surface area product also correlated to the severity of fibrosis as defined by the fibrosis index. In conclusion, the multiple indicator dilution data obtained from the in situ perfused rat liver can be directly related to histopathologic analyses. (HEPATOLOGY 2002;36:1180-1189 L iver fibrosis and cirrhosis represent a major worldwide health problem. In cirrhosis, the normal hepatic lobular architecture is replaced by interconnecting bands of fibrous tissue surrounding nodules of regenerating hepatocytes. The sinusoidal stellate cell is central to the fibrotic process. 1-4 Consequently, extravascular space accessible to macromolecules (e.g., albumin) decreases and the distribution of sucrose shows a barrierlimited pattern in the space of Disse instead of the normal flow-limited behavior due to 3 hepatic alterations: (1) collagenization of the space of Disse, (2) formation of a basement membrane of the sinusoid (capillarization), and (3) intrahepatic, portahepatic shunt formation. 5-8 A liver biopsy is currently mandatory to assess severity of fibrosis.We recently examined the drug structure/disposition kinetics of a series of cationic drugs in carbon tetrachloride-and alcohol-induced fibrosis in perfused rat livers. 9 In this case, cationic drug disposition in the fibrotic liver can be predicted from drug properties and liver histopathology. As a result, the question was raised of whether we could use histopathology from patient liver biopsy specimens to estimate changes in hepatic spaces and whether the active and passive transport of probes (e.g., 3 H-taurocholate, 3 H-water) across ...

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“…70 Both factors lead to HSC activation and collagen deposition. 71,72 Moreover, HCV proteins (i.e., core protein) stimulate secretion of profibrogenic cytokines by hepatocytes and can directly induce fibrogenic actions in HSCs. Although factors such as duration of infection, gender, and alcohol consumption influence fibrosis progression, genetic factors may also play a role.…”

Section: Gene Polymorphisms Influencing Liver Fibrosis In Humansmentioning

confidence: 99%

Genetic polymorphisms and the progression of liver fibrosis: A critical appraisal

2003

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Liver fibrosis is a highly dynamic process in which multiple genes interact with environmental factors. Recent human epidemiologic studies have identified possible polymorphisms in a number of candidate genes that influence the progression of liver fibrosis. These genetic factors could explain the broad spectrum of responses to the same etiologic agent found in patients with chronic liver diseases. Polymorphisms in genes encoding immunoregulatory proteins, proinflammatory cytokines, and fibrogenic factors may influence disease progression in patients with alcohol-induced liver disease, primary biliary cirrhosis, or chronic hepatitis C. However, some of the studies have yielded contradictory results. For example, conflicting results have been obtained in studies assessing the role of mutations in the hemochromatosis gene on fibrosis progression in patients with chronic hepatitis C. Largescale, well-designed studies are required to clarify the actual role of this factor and other genetic variants in liver fibrosis. (HEPATOLOGY 2003;37:493-503.)

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Hepatic stellate cell activation and liver fibrosis are associated with necroinflammatory injury and Thl‐like response in chronic hepatitis C

Abstract: HSC activation and progression of liver injury are unrelated to viral load but associated with a Th1-like response, a plausible target for the treatment of chronic hepatitis C.

Cited by 78 publications

References 49 publications

Combined effect of pro- and anti-inflammatory cytokine gene polymorphisms on susceptibility to liver cirrhosis in Tunisian HCV-infected patients

Combined effect of pro- and anti-inflammatory cytokine gene polymorphisms on susceptibility to liver cirrhosis in Tunisian HCV-infected patients

Quantitative evaluation of altered hepatic spaces and membrane transport in fibrotic rat liver

Genetic polymorphisms and the progression of liver fibrosis: A critical appraisal

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