Thrombin activation and liver inflammation in advanced hepatitis C virus infection

Abstract

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.

The Effect of Viral Clearance Achieved by Direct-Acting Antiviral Agents on Hepatitis C Virus Positive Patients with Type 2 Diabetes Mellitus: A Word of Caution after the Initial Enthusiasm

“…These data suggest that the improvement of extrahepatic manifestations of HCV infection (in particular, cardiovasculopathies and nephropathies) coinciding with the most frequent complications of diabetic disease may improve after viral clearance due not only to glycometabolic control amelioration, but also to other mechanisms yet to be established. In the case of nephropathy, it is likely that HCV eradication may lead to an improvement in vasculitis-cryoglobulinemic damage [56,57]; the beneficial effect of viral eradication on cardiovascular diseases may be derived from the disappearance of the systemic inflammatory status [58], the decrease in TNF-α and IL-6 levels [59,60], and the increase in adiponectin levels [61].…”

Biology of portal hypertension

“…It is not known whether immune cells are directly related to the development of portal hypertension. However, since [132], which promotes activation of factor VIIa and Xa and ultimately prothrombin conversion to thrombin, which converts fibrinogen to fibrin in an intravascular thrombus [133]. Parenchymal extinction may occur due to the presence of this thrombus.…”

Procoagulant imbalance influences cardiovascular and liver damage in chronic hepatitis C independently of steatosis

“…Moreover, we have also shown that the procoagulant imbalance was significantly higher in CHC patients than in controls, even in the absence of severe liver disease. Pro‐inflammatory cytokines, likely increased in CHC, have been associated with plasma hypercoagulability and might therefore contribute to the procoagulant imbalance observed in this study . We therefore hypothesize that HCV infection may activate coagulation through the mediation of pro‐inflammatory cytokines, regardless of the presence of cirrhosis.…”

“…In our cohort we did not find differences in cardiovascular nor in coagulation parameters between CHC patients with and without steatosis, although those with steatosis had a significantly higher prevalence of metabolic abnormalities. It is possible that the procoagulant imbalance, directly modulated by HCV, may represent the trigger mechanism for the process of endothelial and vascular damage in patients with CHC, even in those without metabolic alterations and/or fatty liver, as previously reported …”