studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 945A
1505
Comparison Of Thrombin Generation After Addition Of
Thrombomodulin Or Activated Protein C: Looking For A
Marker Of Hypercoagulability With Low Variability In
Patients With Cirrhosis
Cédric Duron 1 , Armando Abergel 1 , Géraldine Lamblin 1 , Aurelien
Lebreton 2 , Thomas Sinegre 3 ; 1 Hepatogastroenterolgy, CHU, Clermont
Ferrand, France; 2 CHU Clermont Ferrand, Clermont ferrand,
France; 3 CHU Clermont Ferrand, Clermont Ferrand, France
Background and Aims: Cirrhosis is characterized by a defective
hemostasis, and may result in bleeding complications as
well as in thrombotic events. Conventional coagulation tests
such as the Prothrombin Time and aPTT are prolonged in
patients with cirrhosis, assessing only the defects of procoagulants.
Thrombin Generation (TG) testing consist in a dynamic
study of the coagulation, measuring generation and inhibition
of the thrombin by pro and anticoagulant factors. This new
approach reveals that TG could be equal or higher in patients
with cirrhosis than in healthy volunteers. The aim of this study
was: 1) to assess the variability of TG over time, and 2) the
effect of Child-Pugh on TG. Methods: Fifty two patients with a
diagnosis of cirrhosis, without hepatocellular carcinoma, were
included in the study, in 2 groups: uncomplicated cirrhosis and
complicated disease defined by the presence of hemorrhage,
infection or alcoholic hepatitis in the last 3 months. 18 healthy
volunteers were recruited as controls. Patients or controls using
drugs known to modify the coagulation system and/or having
a history of spontaneous thrombosis were excluded. The
stability of TG in platelet-poor plasma testing, with or without
addition of thrombomodulin (TM) or activated Protein C
(PCa), has been assessed over 12 weeks by 3 repeated Calibrated
Automatic Thrombinography measurements at week
0, 6 and 12. Results: The intra-individual variability of endogenous
thrombin potential (ETP) after addition of TM was low,
about 5%, in uncomplicated cirrhosis and healthy volunteers.
The inter-individual variability was about 100%, and was not
influenced by age, sex or cirrhosis etiology (alcoholic or not).
TG, after addition of PCa, varies over time in cirrhosis and
healthy groups. In contrast, TG significantly varies over time
in patients with complicated cirrhosis. TG was significantly
higher in patients with cirrhosis Child B (n=20) than in Child
A (n=21) and healthy volunteers (n=18). No difference was
found between Child B and Child C. The ratio TG without/with
TM increases with hepatic function. No coagulation imbalance
persists after in vitro protein C (PC) normalisation. Conclusions:
TG should be evaluated after addition of thrombomodulin, and
not after addition of activated Protein C in patients with cirrhosis.
Thrombin Generation increased according to the hepatic
function. Thrombin generation over time, in the same patient,
after addition of thrombomodulin should be evaluated as a risk
factor of hypercoagulability. Hypercoagulability appears to be
related to PC deficiency. A largest study should identify factors
affecting inter and intra individual variabilities.
Disclosures:
Armando Abergel - Consulting: gilead, msd, bms; Speaking and Teaching: abbvie
The following authors have nothing to disclose: Cédric Duron, Géraldine Lamblin,
Aurelien Lebreton, Thomas Sinegre
1506
In Vivo Assessment Of Portal Hypertensive Colopathy
And Clinical Outcome Of Patients With Liver Cirrhosis
With Confocal Laser Endomicroscopy (CLE)
Steffen Zopf 1 , Gian Eugenio Tontini 2 , Michael Vieth 3 , Markus
F. Neurath 1 , Helmut Neumann 1 ; 1 Medical Department 1, Friedrich-Alexander
University of Erlangen, Erlangen, Germany; 2 IRCCS
Policlinico San Donato, San Donato Milanese, Italy; 3 Institute of
Pathology, Klinikum Bayreuth, Bayreuth, Germany
Background and Aims: Recent data has highlighted the role
of mucosal integrity for bacterial translocation in the gut which
is also discussed as a major cause for development of spontaneous
bacterial peritonitis (SBP) and/ or hepatic encephalopathy
(HE) in patients with liver cirrhosis. CLE has emerged as a
valuable tool for real time diagnosis of mucosal integrity and
allows in vivo imaging of commensal bacteria in the gut. Our
aim was to prospectively assess the value of CLE for in vivo
diagnosis of portal hypertensive colopathy and its association
to Child-Pugh class, Model for End Stage Liver Disease (MELD),
HE and development of SBP. Methods: Patients with established
diagnosis of liver cirrhosis and portal hypertension were
prospectively included. Clinical, biochemical, and ultrasound
criteria, including portal vein thrombosis, ascites and collateral
portosystemic vessels were assessed in addition to endoscopic
criteria (e.g. esophageal varices, portal gastropathy) and betablocker
intake. Fluoresceine aided CLE was performed in every
patient in the sigmoid colon, rectosigmoid junction, and rectum.
Afterwards biopsies were taken, unless contraindicated,
for corresponding histopathological analysis. Results: Overall,
more than 14,700 CLE images were collected. Confocal
imaging revealed dilation and/or ectasia of microvessels, congestion
of blood flow, edema, and a non-specific increase of
the cellular infiltrate within the lamina propria. These findings
were directly correlated to Child-Pugh class and MELD score
with patients at higher scores showing more distinct changes
of the microarchitecture. Of note, disturbed mucosal integrity,
as observed by CLE, was strongly correlated with occurrence
of HE and SBP, even in the follow-up of the patients. The procedure
was well tolerated by the patients, and no adverse
events were observed. Conclusions: Fluoresceine guided CLE
in patients with liver cirrhosis and portal hypertensive colopathy
is safe and well tolerated. In vivo imaging revealed similar
microscopic changes of portal colopathy as conventional histology
without the need of physical biopsies. Of note, confocal
imaging corresponds to clinical outcome parameters, including
development of HE and/or SPB.
Disclosures:
The following authors have nothing to disclose: Steffen Zopf, Gian Eugenio Tontini,
Michael Vieth, Markus F. Neurath, Helmut Neumann
1507
Conjugated bile acids suppress the HPA axis via activation
of hypothalamic glucocorticoid receptors in a
rodent model of chronic biliary obstruction
Matthew McMillin 1,2 , Gabriel A. Frampton 1 , Stephanie Grant 1 ,
Matthew A. Quinn 3 , Sharon DeMorrow 2,1 ; 1 Texas A&M Health
Science Center, College of Medicine, Temple, TX; 2 Central Texas
Veterans Healthcare System, Temple, TX; 3 Department of Health
and Human Services, National Institute of Environmental Health
Sciences, NIH, Research Triangle Park, NC
Suppression of the hypothalamic pituitary adrenal axis (HPA)
occurs during cholestasis. We previously demonstrated that
serum bile acids gain entry to the hypothalamus in a model
of cholestasis. The aim of the current study was to determine