hepatic venous pressure gradient and platelet activation in chronic liver disease

Conditions: Chronic Liver Disease

Summary: background: thrombosis may be crucial in driving the progression of fibrosis in chronic liver disease (cld). the potential role of platelets and platelet activation in this process is unclear. platelets participate in inflammation by secretion of pro-inflammatory mediators which may advance hepatic fibrosis. hepatitis b virus transgenic mice, developed significantly smaller necroinflammatory foci and their serum alt levels were 80% lower, if they were pre-treated with anti-platelet antibodies. sinusoidal aggregation of activated platelets also occurs in chronic hepatitis c in humans. it may contribute to thrombocytopenia observed in cld. platelet activation is generally believed to be compromised in cld. however, there is data suggesting that cld may even be associated with an enhancement of platelet activation. measurement of hepatic venous pressure gradient (hvpg) constitutes the most common method for estimation of portal venous pressure. hvpg is significantly correlated with histological indices of cld progression. study hypotheses: 1. hvpg as a marker for advancement of hepatic fibrosis and progression of cld is associated with an increase in platelet activation. 2. platelet activation and function is not generally compromised in cld. comparison of platelet function in cld to a control group of healthy volunteers is intended to clarify whether cld leads to a manifest platelet dysfunction methods: study design is observational. 100 patients with cld of various origins (viral, alcoholic, cholestatic) scheduled for routine hvpg measurement will be enrolled. 30 healthy volunteers will donate blood as a control group. platelet function and activation will be evaluated by multiple electrode aggregometry (primary outcome variable area under the curve (auc). plasma levels of p-selectin (elisa), pfa (platelet function analyzer) 100™ parameters (epi-ct and adp-ct), percentage of p-selectin, gpiib/iiia, thrombin receptor positive platelets after stimulation (flow-cytometry) will constitute secondary outcome parameters. plasmatic coagulation will be evaluated by rotational thrombelastometry (rotem). platelet count and routine coagulation parameters will be monitored. hvpg measurement by hepatic vein catheterization and patient blood sampling will be carried out via the internal jugular vein. blood sampling in volunteers will be performed via the antecubital vein study rationale: if higher levels of platelet activation are associated with increased hvpgs, this would provide an insight into the pathogenesis of cld. it would also point toward a possible benefit of anti-platelet therapy in cld. verification of platelet dysfunction in cld is relevant to clinical practice in anaesthesiology and intensive care as procedures are often postponed in cld-patients for fear of bleeding complications. cld patients may also receive prophylactic platelet concentrates prior to interventions which is costly, fraught with risk of bacterial infection and may be unnecessary in the absence of platelet dysfunction.


Eligibility criteria:
inclusion criteria: * confirmed chronic liver disease (cld), alcoholic, viral, cholestatic. * child-pugh stage a, b, c, and non-cirrhotics * planned routine measurement of hvpg. * age: 19 years or older exclusion criteria: * impaired kidney function (creatinine \> 1.3mg/dl) * platelet count \< 50,000/µl * participation in a clinical trial in the 3 weeks preceding the study * ifn-therapy within 6 months of inclusion into the study. * use of anti-thrombotic or anticoagualant medication * pregnancy * intra or extra-hepatic malignancy * haemostatic diseases other than cirrhosis * current abuse of alcohol (abstinence from alcohol for at least 6 weeks preceding the study is required)

Keywords: chronic liver disease cld platelet function