studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 517A
increased CD4 + and CD8 + T cells compared to 2-OA-BSA/PBS
immunized mice. The frequencies of CD44 expressing CD8 +
T cells and CD69 expressing CD8 + T cells were significantly
increased in 2-OA-BSA/OCH immunized mice compared to
2-OA-BSA/PBS immunized mice. Moreover, the frequency of
CD44 expressing CD4 + T cells was significantly increased in
2-OA-BSA/OCH immunized mice. Furthermore, the levels of
AMA, cell infiltrates, and IFN-γ production of liver mononuclear
cells were decreased in CD1d -/- mice when compared with
wild type mice. Conclusion: Activation of iNKT cells is critical
for the natural history of autoimmune cholangitis in this model
and highlights the role of innate immunity in human PBC.
Disclosures:
The following authors have nothing to disclose: Chao-Hsuan Chang, Ying-chun
Chen, Weici Zhang, Patrick S. Leung, M. Eric Gershwin, Ya-Hui Chuang
620
Serum metabolomic profile of patients with primary
biliary cirrhosis treated with bezafibrate and changes
following itching relief
Albert Pares 1 , Anna Reig 1 , Miriam Perez-Cormenzana 2 , Rebeca
Mayo 2 , Pilar Sese 1 , Azucena Castro 2 ; 1 Liver Unit, Hospital Clinic,
University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain;
2 OWL, Derio, Spain
Background and aims: Long-term fibrate treatment is an effective
therapy for patients with primary biliary cirrhosis with
suboptimal biochemical response to ursodeoxycholic acid.
Bezafibrate therapy has further effects, thus decreasing pruritus
in this cholestatic condition. The metabolomic consequences
of fibrates in PBC are not known, and some studies indicate
that their action may result from being a PPAR alpha agonist
and also increasing the expression of some bile acid transporters.
Therefore, we have assessed the metabolomic profiling of
patients under bezafibrate, and particularly in those with pruritus,
to define the potential mechanisms of action of bezafibrate
in this cholestatic disease. Patients and Methods: Serum samples
before and after bezafibrate therapy were taken from 29
patients with PBC. Moreover in 14 of these patients with pruritus,
samples were obtained before, during and after bezafibrate
discontinuation. Metabolite extraction was accomplished
by fractionating the samples into pools of species with similar
physicochemical properties. Three different UPLC-MS analytical
platforms were used for the analysis of fatty acyls, bile acids,
steroids and lysoglycerophospholipids; amino acids; glycerolipids,
glycerophospholipids, sterol lipids and sphingolipids.
Results: More than 530 metabolites were identified. Regarding
individual species 93 metabolites changed during bezafibrate
therapy: PE(0:0/16:1) and ChoE(16:1) were in higher concentrations,
while PC(17:0/18:2), PC(17:0/0:0), PC(15:0/22:6),
PC(18:3/18:3) and PC(18:0/20:4) decreased with bezafibrate.
Pruritus disappeared or was minimized by bezafibrate.
In these patients 38 metabolites decreased (p