studies

1226A AASLD ABSTRACTS HEPATOLOGY, October, 2015
2087
Polymorphisms in the interleukin (IL)-1 gene cluster are
associated with multiple markers of systemic inflammation
in patients with Acute-on-Chronic Liver Failure
(ACLF)
Jose Alcaraz-Quiles 1 , Esther Titos 4 , Cristina Lopez-Vicario 1 ,
Bibiana Rius 1 , Aritz Lopategi 1 , Mireia Casulleras 1 , Veronica
Garcia-Alonso 1 , Andrea De Gottardi 5 , Mauro Bernardi 3 , Ivo Graziadei
6 , Henning Gronbaek 7 , Pere Gines 8,4 , Vicente Arroyo 8,2 ,
Joan Clària 1,2 ; 1 Department of Biochemistry and Molecular Genetics,
Hospital Clínic-University of Barcelona, Bareclona, Spain;
2 University of Barcelona, Barcelona, Spain; 3 EASL-CLIF Consortium,
Barcelona, Spain; 4 CIBERehd, Barcelona, Spain; 5 University
of Berne, Berne, Switzerland; 6 Innsbruck Medical University,
Innsbruck, Austria; 7 Aarhus University Hospital, Aarhus, Denmark;
8 Liver Unit, Hospital Clinic, Barcelona, Spain
Background and aim: Acute-on-Chronic liver failure (ACLF) is
an increasingly recognized entity encompassing multiorgan
failure in patients with cirrhosis. Recent findings suggest that
immune dysregulation predisposes decompensated cirrhotic
patients to a cycle of adverse events culminating in uncontrolled
systemic inflammation and ACLF progression. Although
the exact mechanisms leading to inflammation-driven ACLF
remain to be elucidated, systemic inflammation is influenced by
multiple genes regulating the innate immune response. In this
study, we screened a set of six inflammation-related genes in
a population-based study of patients with decompensated liver
cirrhosis. Patients and Methods: Two hundred seventy-nine cirrhotic
patients (178 with ACLF and 101 without ACLF) from the
CANONIC study of the CLIF consortium were genotyped for
SNP polymorphisms in genes coding for IL-1beta (rs1143623,
G/C), IL-1 receptor antagonist (IL-1Ra) (rs4251961, T/C),
SOCS3 (rs4969170, G/A), NOD2 (rs3135500, G/A),
CMKLR1 (rs1878022, T/C) and IL-10 (rs1800871, G/A) by
allellic discrimination TaqMan assays. Serum cytokine levels
were measured by fluorescent bead-based (Luminex) immunoassays.
Results: Among the six SNPs analyzed, we identified
two polymorphisms belonging to the IL-1 gene cluster (IL-1beta,
rs1143623 and IL-1Ra, rs425196) in strong association with
ACLF. Homozygous C carriers in the rs1143623 SNP showed
lower serum levels of IL-1β in parallel with reduced markers
of systemic inflammation (i.e. IL-1alpha, IL-6 and TNF-alpha).
Also, heterozygous TC carriers of the rs425196 SNP had
lower serum levels of IL-1beta, IL-1alpha, IL-6, TNF-alpha and
IL-8. Under different inheritance models, both genotypes were
protective factors for presence of ACLF (rs1143623; OR: 0.34,
p