In vitro potency of clinically used antiplatelet drugs in patients with Metabolic dysfunction Associated Fatty Liver Disease

Metabolic dysfunction Associated Fatty Liver Disease (MAFLD) is the most common
cause of liver disease worldwide, with an estimated prevalence of 9-36.9% in
the general population(1). It is regarded to as the hepatic manifestation of
metabolic syndrome, a syndrome characterised by increased blood pressure, high
blood sugar, excess body fat around the waist and abnormal cholesterol or
triglyceride levels. The term MAFLD comprises of a spectrum of pathologic
entities, varying from the benign presence of hepatic steatosis (HS) to the
chronic inflammatory disease Non-Alcoholic Steatohepatitis (NASH), ultimately
leading to cirrhosis.
The role of MAFLD as an adjunctive risk factor for the development of
cardiovascular diseases (CVD) has been debated for a long time. Recent evidence
has however demonstrated an existing relationship between these two conditions,
as well as the association between MAFLD and traditional CVD risk factors such
as type 2 diabetes and obesity. A meta-analysis involving 34.043 adult
individuals has shown that patients with MAFLD have an increased risk of both
fatal and non-fatal cardiovascular events (OR 1.64, 95% CI 1.26-2.13) compared
to patients without MAFLD. Moreover, a further increase in the risk of
cardiovascular events (OR 2.58, 95% CI 1.78-3.75) was observed among patients
with more *severe* MAFLD(2).
Therapeutic modalities to improve of prevent MAFLD and/or liver
fibrosis in general are insufficient, and current interventional strategies are
mainly focused on lowering cardiovascular risk. These interventions mainly
involve lipid lowering agents, antidiabetic drugs and antihypertensives(3). The
role for antiplatelet therapy in cardiovascular primary prevention remains
controversial, with potential benefits limited by an increased bleeding
risk(4). There is however increasing evidence that supports the use of
antiplatelet therapy as primary prevention in high risk cases, such as in
patients with type 2 diabetes and MAFLD, provided that the risk of bleeding is
low(5-7).
Even though prophylactic antiplatelet therapy might thus be indicated
in a high risk patient population with MAFLD, and is even associated with lower
risk for progression to advanced fibrosis with time(8,9), its* efficacy in
patients with MAFLD has yet to be determined. Chronic liver disease, including
MAFLD, is associated with complex changes of the haemostatic system, such as
decreased coagulation factors and fibrinolysis, but also thrombocytopaenia and
altered platelet function(10,11). Data on the effect of this altered
haemostasis on the potency of antiplatelet drugs is however lacking. Given that
current guidelines do not take the altered haemostasis in patients with MAFLD
into account, the objective of this study is therefore to evaluate the in vitro
potency of clinically used antiplatelet drugs in these specific patients.

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To compare the in vitro potency of commonly used antiplatelet drugs in the
blood of patients with various stages of fibrosis due to MAFLD, compared to
that in blood of individuals without underlying liver disease.

This study is a prospective cross-sectional study. Patients with various stages
of Metabolic dysfunction Associated Fatty Liver Disease will be recruited at
the outpatient clinics or whilst admitted to University Medical Center
Groningen. Additionally, healthy controls will be recruited.

There are no expected adverse events or serious adverse events associated with
participation in this study. Minor bruising or discomfort at the site of
venepuncture might occur. The amount of blood taken from participants is 27 mL,
which will not harm the participants in any way.