studies

850A AASLD ABSTRACTS HEPATOLOGY, October, 2015
αEβ7 suggest homing to the peri-biliary region where LI MAIT
cells are activated in response to bacteria-exposed BEC in an
MR1 dependent manner, leading to liver injury through their
release of cytolytic enzymes and inflammatory cytokines.
Disclosures:
David H. Adams - Advisory Committees or Review Panels: GSK, Proximagen;
Grant/Research Support: Takeda, Biotie Therapies, Novimmune, ChemoCentryx,
Novimmune, Biotie Therapies; Patent Held/Filed: biotie therapies, Biotie Therapies,
Biotie Therapies, Biotie Therapies, Biotie Therapies, Biotie Therapies, Biotie
Therapies, Biotie Therapies
The following authors have nothing to disclose: Hannah C. Jeffery, Bonnie Van
Wilgenburg, Kathryn Stirling, Krishan Parekh, Sheree Roberts, Ayako Kurioka,
Stuart Hunter, Paul Klenerman, Ye H. Oo
1299
Alterations in liver dendritic cell subtypes during non-alcoholic
steatohepatitis
Eva-Carina Heier, Hannes Borchardt, Henrike Julich, Christoph
Eckert, Niklas Klein, Thomas Tschernig, Veronika Lukacs-Kornek;
Department of Medicine II, Saarland University, Homburg, Germany
BACKGROUND/AIMS: Dendritic cells (DCs) represent a heterogeneous
subpopulation that is primarily identified as
CD11c + MHCII + cells in the liver. However, these markers are
not exclusively identifying DCs rather they are relevant to a
mixture of myeloid/lymphoid cells. Nevertheless, CD11c + cells
limited inflammation by reducing the destructive effect of innate
cells and promoting the clearance of cellular debris in non-alcoholic
steatohepatitis (NASH). The various DC subsets have different
roles in liver homeostasis and divergent factors determine
their functional operation during inflammation (Lukacs-Kornek
V. J Hepatol. 2013 Nov;59(5):1124-6). In order to clarify the
nature and subset of DCs involved in NASH, the study aimed
to characterize the CD11c + myeloid infiltrates and dissect the
role of the various DC subtypes during disease progression.
METHODS: CD11c + cell infiltrate was analyzed in methionine
choline deficient (MCD) diet induced liver steatohepatitis in the
progression and regression phase. Using multicolor FACS analyses,
the myeloid compartment was mapped during disease
progression and the individual DC subtypes, and precursor
DCs were identified and distinguished from monocytes, macrophage
and neutrophils. RESULTS: During disease progression,
CD11c + cells were increased and among these cells, the
CD11c + CD11b + myeloid DC subtype increased an average of
2.1 fold in 1wk and 2.2 fold in 5wks MCD treated animals.
Not only the myeloid but also the lymphoid DC subtypes followed
similar changes. Accordingly, the frequency of lymphoid
DCs (CD103 + CD11c + CD11b - ) increased during disease progression
(2.2 and 2.3 fold increase in 1wk and 5wks MCD
treated animals). During regression of steatohepatitis, these
changes were reduced and after 1wk of regression period
DC parameters were similar to control animals. Functionally,
both DC subtypes produced high amount of inflammatory cytokines
(e.g. TNFα), (30%-40% of myeloid DCs and 10% of lymphoid
DCs). Besides, the precursor DC population was more
abundant in 1wk MCD treatment and further elevated in 5wks
MCD treatment. CONCLUSIONS: During MCD diet induced
steatohepatitis both DC subtypes show increased abundance
and exhibited similar fold changes suggesting the importance
of both DC subtypes in the pathomechanism of NASH. DC
changes are paralleled by alterations observed in the precursor
DC population suggesting the relevance of local DC differentiation
during steatohepatitis. Studies were supported by
the Alexander von Humboldt Foundation – Sofja Kovalevskaja
Award 2012 to VLK.
Disclosures:
The following authors have nothing to disclose: Eva-Carina Heier, Hannes
Borchardt, Henrike Julich, Christoph Eckert, Niklas Klein, Thomas Tschernig,
Veronika Lukacs-Kornek
1300
Soluble CD163 plasma concentration is related with
necroinflammatory activity and liver function impairment
in compensated cirrhotic patients and is not
related with bacterial translocation
Francesco Figorilli 2,1 , Karen Louise Thomsen 2 , Jane Mac-
Naughtan 2 , I.Jane Cox 3 , Alba Moratalla 4 , Isidora Ranchal 2 ,
Holger J. Møller 5 , Rajeshwar Mookerjee 2 , Nathan Davies 2 , Rajiv
Jalan 2 ; 1 Universita’ di Cagliari, Cagliari, Italy; 2 Liver Failure
Group, UC, Institute for Liver and Digestive Health, UCL Medical
School, Royal Free Campus, London, United Kingdom; 3 nstitute of
Hepatology, London, Foundation for Liver Research, 69-75 Chenies
Mews, London, United Kingdom; 4 Liver unit, Hospital General
Universitario de Alicante, CIBER de Enfermedades Hepáticas y
Digestivas (CIBERehd), Alicante, Spain; 5 Department of Clinical
Biochemistry, Aarhus University Hospital, Aarhus, Denmark
Background: CD163 is a scavenger receptor expressed on
monocytes and macrophages e.g. Kupffer cells in the liver.
Plasma levels of soluble CD163 (sCD163, normal range 0.89-
3.95 mg/L) are associated with macrophage activation and
grade of portal hypertension and provide prognostic information
in cirrhosis. The mechanism underlying this increase
in sCD163 is not clear. In this study we aimed to determine
whether there was a relationship between the level of sCD163
and gut permeability and markers of bacterial translocation
or severity of liver disease. Methods: 66-clinically-stable liver
cirrhosis out-patients were included (Male 69.7%; Age 57
±9.15; Alcoholic liver disease 57.6%). Exclusion criteria were
a Child Pugh score >10 and clinical or microbiological evidence
of infection 7 days prior to enrolment. sCD163 plasma
level was measured by an ELISA test, gut permeability using
the lactulose/rhamnose test, bacterial DNA by PCR reaction
and LPS concentration was obtained by HEK-Blue LPS Detection
Kit 2s. Urine was collected for proton magnetic resonance
spectroscopy ( 1 HMRS). Patients were divided accordingly to
their sCD163 level (3.95). For the statistical analysis
we used Chi-square, Student T-test, Man Whitney test and
Spearman correlation. Results: The median value of sCD163
was 4.33mg/L with a range of 1.44-15.43. We did not find
any significant correlation between the levels of sCD163, gut
permeability (0.028, range 0.002-0.112), or LPS concentration
(0.02ng/ml, range 0-14.1). There was no difference in
the prevalence of bacterial DNA positivity in patients with an
abnormal value of sCD163 (11.1% vs. 2.6%). 39/66 (59.1%)
patients with a sCD163>3.95mg/L showed a significant
higher MELD value (9.0 vs. 7.5) and higher levels of AST (43
vs. 30 U/L), ALP (102 vs. 70U/L), GGT (98 vs. 48 U/L) and
lower level of platelets (107 vs. 178 x 10 9 ). Child-Pugh B was
more common in patients with high sCD163 levels (17,9 vs.
0%)). No significant differences were observed between the
two groups regarding aetiology, alcohol consumption, drug
use, comorbidity, previous episode of liver decompensation or
infection in the previous month. At 1 HMRS analysis, patients
with sCD163>3.95 showed no significant difference in urinary
level of hippuric acid, formate, citrate or lactate. Conclusion:
Our results suggest that Kupffer cell activation is an early
event in the pathogenesis of chronic liver disease, which is
not dependent of gut permeability or bacterial translocation.
sCD163 concentration might reflect the grade of necroinflammation
and liver function impairment in compensated cirrhotic
patients.