Role of hypercoagulability and hypofibrinolysis in the progression of hepatic fibrosis

Hepatic fibrosis, or scarring of the liver, is the result of chronic damage to
the liver in response to a variety of causes, the most important being
non-alcohol fatty liver disease (NAFLD), viral hepatitis and alcohol abuse.
Fibrosis of the liver is a major cause of morbidity and mortality. Patients
with advanced fibrosis or cirrhosis have an increased risk of developing
hepatocellular carcinoma (HCC). Several lines of evidence suggest that fibrosis
formation is increased in the setting of a hypercoagulable phenotype. This
project will focus on the role of prothrombotic factors in the development and
progression of liver fibrosis in the general population. Most evidence stems
from small studies and the exact role of hypercoagulability in hepatic
fibrogenesis, both in the general population and in cases with underlying
parenchymal liver disease, remains to be elucidated.

To study the association between hypercoagulability and liver fibrosis.

It concerns a single-center case control study conducted by the department of
Gastroenterlogy and Hepatology in cooperation with the department of Hematology
and department of Epidemiology at the Erasmus MC, Rotterdam.
All participants of the Rotterdam Study will be screened for presence of liver
fibrosis using non invasive ultrasound and transient elastography (Fibroscan®),
as embedded in the core protocol of the Rotterdam Study. Participants with
advanced fibrosis, defined by a Fibroscan value >10.5 kPa in the presence of
steatosis and > 12.5 kPa in the absence of steatosis will be invited for
participation in our study when they visit the Hepatology and Gastroenterology
Outpatient Clinic of the Erasmus MC for necessary follow-up (an expected 350
cases). A limited amount of blood will be obtained in at least 146 cases (the
alculated sample size for 90% power) for the study of parameters involved in
the pathways of coagulation and fibrinolysis. We will match every case with a
control from the same cohort (with no or mild hepatic fibrosis, defined by a
Fibroscan value < 5 kPa) for age, gender, alcohol consumption and BMI.

Participants will not derive any personal medical benefits from participating.
Blood will be with drawn one single time. The amount of blood withdrawn is
within the amounts acceptable by the institution. Patients visiting the
Gastroenterology and Hepatology Outpatient Clinic will have their additional
blood draw together with a regular blood draw.
Liver biopsies will only be obtained as part of standard diagnostic follow-up
in subjects with advanced fibrosis. Therefore, there are no additional risks
involved for participants.