Thrombin activation and liver inflammation in advanced hepatitis C virus infection

Hepatitis C virus(HCV) infection is associated with increased thrombotic risk. Several mechanisms are involved including direct endothelial damage by the HCV virus, with activation of tissue factor, altered fibrinolysis and increased platelet aggregation and activation. In advanced stages, chronic HCV infection may evolve to liver cirrhosis, a condition in which alterations in the portal microcirculation may also ultimately lead to thrombin activation, platelet aggregation, and clot formation. Therefore in advanced HCV liver disease there is an increased prevalence of thrombotic phenomena in portal vein radicles. Increased thrombin formation may activate hepatic stellate cells and promote liver fibrosis. In addition, ischemic changes derived from vascular occlusion by microthrombi favor the so called parenchymal extinction, a process that promotes collapse of hepatocytes and the formation of gross fibrous tracts. These reasons may explain why advanced HCV infection may evolve more rapidly to end-stage liver disease than other forms of cirrhosis.

Liver steatosis in hepatitis C patients

There is controversy regarding some aspects of hepatitis C virus(HCV) infection-associated liver steatosis,and their relationship with body fat stores. It has classically been found that HCV,especially genotype 3,exerts direct metabolic effects which lead to liver steatosis. This supports the existence of a so called viral steatosis and a metabolic steatosis,whichwould affect HCV patients who are also obese or diabetics. In fact,several genotypes exert metabolic effects which overlap with some of those observed in the metabolic syndrome. In this review we will analyse the pathogenic pathways involved in the development of steatosis in HCV patients. Several cytokines and adipokines also become activated and are involved in "pure" steatosic effects,in addition to inflammation. They are probably responsible for the evolution of simple steatosis to steatohepatitis,making it difficult to explain why such alterations only affect a proportion of steatosic patients.

Adipokines,cytokines and body fat stores in hepatitis Cvirus liver steatosis

AIM: To identify patients with or without liver steatosis and its severity in treatment-na?ve patients affected by hepatitis C virus(HCV) infection.METHODS: We included 56 HCV infected patients, and assessed the amount of liver fat by histomorphometry, and its relationships with fat and lean mass at different parts of the body(by densitometry), hormones [insulin, homeostatic model assessment(HOMA)], adipokines(resistin, adiponectin, leptin), and cytokines(tumor necrosis factor α, interleukin-6).RESULTS: Although the intensity of liver steatosis is related to trunk fat mass and HOMA, 33% of patients showed no liver steatosis, and this finding was not related to body mass index or genotype. Besides trunkfat mass, no other factor was related to the presence or not of liver steatosis, or to the intensity of it, by multivariate analysis. Lean mass was not related to liver steatosis. Adiponectin levels were lower among patients. No differences were observed in leptin and resistin.CONCLUSION: Steatosis in HCV infection is common(67.2%), and closely related to trunk fat, and insulin resistance, but not with leg fat mass or adipokines.