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

Abstract

Background & Aims:Patients with chronic HCV infection besides hepatitis often present cardiovascular damage, the pathogenesis of which is not defined. In chronic liver diseases, including NAFLD and cirrhosis, a procoagulant imbalance, potentially responsible for atherosclerosis has been reported. We aimed at evaluating whether a procoagulant imbalance is present also in non-cirrhotic patients with HCV infection and whether the procoagulant imbalance correlates with cardiovascular damage.The correlation between the procoagulant imbalance, coexisting steatosis, and liver fibrosis was analysed.Methods: From 2014 to 2018, 393 subjects (205 patients with chronic HCV infection from two liver units and 188 controls) were enrolled. Metabolic, cardiovascular, liver assessment and coagulation parameters-procoagulants (FII and FVIII) and anticoagulants (antithrombin and protein C [PC]), endogenous thrombin potential (ETP), peak-thrombin and their ratios (with/without thrombomodulin)-were determined. Results:The procoagulant imbalance (defined as high FVIII, FVIII/PC ratio, ETP-ratio and peak-thrombin-ratio (with/without thrombomodulin)) was significantly higher in patients with chronic HCV than controls. Steatosis was detected in 87 patients (42%).No difference in coagulation imbalance, carotid and cardiac parameters and severity of liver fibrosis was observed in patients with or without steatosis, despite the latter had less severe metabolic alterations. The FVIII/PC ratio was independently associated with carotid intima-media thickness (coefficient 0.04, 95% CI 0.002-0.07, P = .04) and liver fibrosis (coefficient 0.64, 95% CI 0.37-0.92, P < .0001). Conclusion: Patients with HCV infection, even in the absence of cirrhosis have a procoagulant-imbalance that possibly plays a role in increasing the risk of cardiovascular disease and progression of fibrosis. How to cite this article: Sigon G, D'Ambrosio R, Clerici M, et al. Procoagulant imbalance influences cardiovascular and liver damage in chronic hepatitis C independently of steatosis. Liver

Clinical and genetic determinants of the fatty liver–coagulation balance interplay in individuals with metabolic dysfunction

“…Similarly, liver fibrosis, but not steatosis, was associated with a procoagulant imbalance in chronic hepatitis C patients. 28 However, we could not assess and draw conclusions on the regulation of fibrinolysis, which in a recent study was found impaired in non-diabetic patients with NAFLD, 29 and on the role of neutrophil extracellular traps in triggering coagulation in participants with liver inflammation. 30 Notwithstanding, the present results seem to confirm that subclinical systemic inflammation (CRP levels) impact on the coagulation balance at different levels, 31 even in this cohort of apparently healthy and asymptomatic individuals, but most importantly showed that the association of early liver damage with procoagulant imbalance is independent of CRP.…”

Predicting de‐novo portal vein thrombosis after HCV eradication: A long‐term competing risk analysis in the ongoing PITER cohort

“…Since slow portal blood flow is a major risk factor for the development of PVT, 2 this might partly explain the low incidence of PVT in our cohort. Virological cure might lead to an improvement in HCV‐associated hyper‐coagulability 13,14,36 and a decrease in the thrombotic tendency associated with cirrhosis 37 . Patients with more advanced liver disease in whom SVR seems not to be associated with a significant reversal of coagulopathy 13 would remain at risk of thrombosis.…”

Association between liver fibrosis and thrombotic or bleeding events in acute coronary syndrome patients

“…And we found that LFS could predict thrombotic events in ACS patients but not bleeding events. Procoagulant imbalance is common in people with chronic liver disease, even those with mildly elevated liver fibrosis scores [ 33 ]. Inflammatory status, elevated thrombophilic factors, endothelial dysfunction, and oxidative injury in liver fibrosis or cirrhosis lead to hypercoagulable and thrombotic state [ 34 , 35 ], increasing ischemic events risk.…”