studies

510A AASLD ABSTRACTS HEPATOLOGY, October, 2015
nostic groups. To evaluate each analyte as a classifier, receiver
operating characteristic (ROC) curves were constructed and the
area under the curve (AUC), sensitivity, and specificity were
calculated as classifier performance metrics. Multinomial logistic
regression coupled with a forward stepwise selection procedure
and a leave-one-out cross validation analysis was then
used to select analytes for inclusion into composite classifiers.
RESULTS: Importantly, this methodology is strikingly more sensitive
and indeed there were 30 glycoconjugates differentially
expressed between PBC and controls, 27 between PSC and
controls, and 20 between PBC and PSC. Age contributed to
the expression of 25 glycoconjugates. Multi-analyte classifiers
designed as disease-specific (i.e. PBC vs control, PSC vs control,
and PBC vs PSC) diagnostic tests were able to perform their
designated tasks perfectly (AUCs, sensitivities and specificities
of 1). CONCLUSIONS: Glycosylation is significantly altered in
patients with PBC. Glycoconjugates can serve as sensitive and
specific biomarkers capable of distinguishing between specific
autoimmune diseases. Indeed, future work can be used to focus
not only on diagnosis, but also as biomarkers for disease severity
and prognosis.
Disclosures:
L. Renee Ruhaak - Employment: Intel
Christopher L. Bowlus - Advisory Committees or Review Panels: Gilead Sciences,
Inc; Grant/Research Support: Gilead Sciences, Inc, Intercept Pharmaceuticals,
Bristol Meyers Squibb, Takeda, Lumena, Merck; Speaking and Teaching: Gilead
Sciences, Inc
The following authors have nothing to disclose: Kyoungmi Kim, Sandra L. Taylor,
Qiuting Hong, Forum Patel, Carol Stroble, Patrick S. Leung, Michiko Shimoda,
M. Eric Gershwin, Carlito B. Lebrilla, Emanual Maverakis
607
Phenotypic Variations in Primary Sclerosing Cholangitis
Across the Age Spectrum
John E. Eaton 1 , Brian D. Juran 1 , Elizabeth J. Atkinson 2 , Bryan
McCauley 2 , Erik M. Schlicht 1 , Mariza de Andrade 2 , Velimir A.
Luketic 8 , Joseph A. Odin 3 , Ayman A. Koteish 4 , Kris V. Kowdley 5 ,
Kapil B. Chopra 6 , Gideon Hirschfield 7 , Naga P. Chalasani 9 , Konstantinos
Lazaridis 1 ; 1 Gastroenterology and Hepatology, Mayo
Clinic, Rochester, MN; 2 Biomedical Statistics and Informatics,
Mayo Clinic, Rochester, MN; 3 Gastroenterology and Hepatology,
Icahn School of Medicine at Mount Sinai, New York, NY; 4 Gastroenterology
and Hepatology, Johns Hopkins, Baltimore, MD; 5 Liver
Care Network, Swedish Medical Center, Seattle, WA; 6 Gastroenterology
and Hepatology, University of Pittsburgh, Pittsburgh, PA;
7 Centre for Liver Research and NIHR Biomedical Research Unit,
University of Birmingham, Birmingham, United Kingdom; 8 Gastroenterology
and Hepatology, Virginia Commonwealth University,
Richmond, VA; 9 Gastroenterology and Hepatology, Indiana University
School of Medicine, Indianapolis, IN
Background & Aims: Primary sclerosing cholangitis (PSC) typically
develops in middle-aged men. However, it is unknown if
phenotypic differences exist among patients diagnosed with
PSC at various ages. To this end, we compared the clinical
characteristics of a PSC cohort based on the age when PSC
was diagnosed. Methods: We performed a patient survey
and a medical record review to compare the phenotypic features
of PSC patients (n=967) who were diagnosed between
1-19 years (yrs) (early onset, n=108), 20-59 yrs (middle age
onset, n=763), and 60-79 yrs (late onset, n=96). Patients were
recruited prospectively from 8 academic medical centers in
North America. Results: There were no demographic differences
between groups. However, those with early onset-PSC
were more likely to have ulcerative colitis (UC) (61.1%) compared
to the middle age onset (54.1%) and late onset (40.6%)
groups (p=0.01). Similarly, concomitant autoimmune hepatitis
was more common in early onset-PSC when compared to
the other groups (13.9% vs. 4.8% for middle age onset and
7.3% for late onset, p=0.001). Cholangiocarcinoma (CCA)
was diagnosed in 54 PSC patients (early onset 0%, middle age
onset 7% and late onset 8.3%). While CCA in early onset-PSC
appears to be rare, we did not detect a statistically significant
difference between groups and the overall development
of CCA (log rank p value=0.32). However, those with late
onset-PSC were more likely to be diagnosed with CCA within a
year of their PSC diagnosis when compared to the other groups
(early onset 0%, middle age onset 2.5% and late onset 6.2%,
p = 0.02). Two-hundred and eleven individuals underwent a
liver transplantation (early onset 14%, middle age onset 25%
and late onset 6.2%) and survival free from liver transplant was
similar between groups after adjusting for PSC duration and
gender (late onset vs. early onset: [Hazard ratio] HR; 2.1, 95%
Confidence Interval [CI]: 0.8-5.7, p: 0.15; middle age onset
vs. early onset: HR; 0.8, 95% CI: 0.5-1.5, p=0.50). Lastly,
early onset-PSC was associated with a higher proportion of
second-degree relatives with inflammatory bowel disease (IBD)
when compared to the other groups (19.4% vs. 6.8% for middle
age onset and 2.1% for late onset, p