studies

526A AASLD ABSTRACTS HEPATOLOGY, October, 2015
around these tools particularly amongst non-specialists. Implementing
a stratified approach to management requires these
gaps to be addressed.
Disclosures:
David Jones - Consulting: Intercept, Pfizer, Novartis; Speaking and Teaching:
Falk, Shire
Gideon Hirschfield - Advisory Committees or Review Panels: Intercept Pharma;
Consulting: Dignity Sciences, GSK, NGM Bio, Lumena, J & J; Grant/Research
Support: BioTie; Speaking and Teaching: Falk Pharma
The following authors have nothing to disclose: Margaret Corrigan, Luke Vale,
Diarmuid Coughlan
Disclosures:
Richard Pencek - Employment: Intercept Pharmaceuticals; Stock Shareholder:
Intercept Pharmaceuticals
Tonya Marmon - Employment: Intercept Pharmaceuticals, Inc; Stock Shareholder:
Intercept Pharmaceuticals, Inc
The following authors have nothing to disclose: Karen Lutz, Leigh MacConell
636
Clinician confidence in stratifying risk in primary biliary
cirrhosis – a UK-PBC survey
Margaret Corrigan 1 , Luke Vale 2 , Diarmuid Coughlan 2 , David
Jones 3 , Gideon Hirschfield 1 ; 1 NIHR Liver Biomedical Research
Unit, University of Birmingham, Birmingham, United Kingdom;
2 Institute of Health and Society, Newcastle University, Newcastle,
United Kingdom; 3 Institute of Cellular Medicine, Newcastle Uiniversity,
Newcastle, United Kingdom
Background: Primary biliary cirrhosis (PBC) has only one present
licensed therapy, ursodeoxycholic acid (UDCA). Future
therapies will be offered to patients at high risk of disease progression.
Assessment of biochemical response to UDCA allows
identification of high risk patients. Aim: To survey current
understanding of UDCA response criteria in the UK. Methods:
A survey of current clinical practice was created by UK-PBC
and distributed to clinicians via the British Society of Gastroenterology
(BSG) and British Association for the Study of the
Liver (BASL) mailing lists and newsletters. 206 responses were
received from 1900 invites. Questions covered diagnosis and
management of the condition with four questions specifically
covering UDCA response assessment. Results: Respondents
came from a variety of clinical backgrounds - consultant hepatologists
in tertiary centres – 14 (7%), consultant hepatologists
in non tertiary centres – 32 (15.5%), consultant gastroenterologists
– 75 (36.4%), trainees – 78 (37.9%), others including specialist
nurses - 7 (3.4%). Whilst 90% of respondents reported
routine use of UDCA in clinical practice, only 20% reported
always assessing UDCA response once patients have been
on treatment for 12 months whilst 50% never assess response.
Looking at rates of assessment of UDCA response between the
specialist groups: 64% of gastroenterologists and 47% trainees
never assess response compared to 25% of non-tertiary
hepatologists and 14% of tertiary hepatologists. The number of
patients seen appeared to affect UDCA response assessment:
64% of those who saw fewer than 10 patients/year never
assess response compared to 10% of those who saw more than
50 patients/year. 40% of respondents reported themselves as
‘not all confident’ in assessing response with 58% stating they
were unaware that criteria were available and 27% unsure
which criteria were best to use. Conclusion: The majority of
patients with PBC are cared for in non-tertiary centres and most
are managed by non-specialist clinicians. The application of
emerging therapies for patients with PBC requires appropriate
use of risk stratification tools in routine clinical practice.
Our results demonstrates gaps in knowledge and confidence
637
The IgG/IgG4 mRNA ratio by quantitative PCR accurately
diagnoses IgG4-related disease and predicts
treatment response
Lowiek M. Hubers 1 , Marieke E. Doorenspleet 2,3 , Emma L. Culver
4,5 , Lucas Maillette de Buy Wenniger 1 , Paul L. Klarenbeek 2,3 ,
Roger W. Chapman 4,5 , Stan F. van de Graaf 1 , Joanne Verheij
6 , Thomas van Gulik 7 , Frank Baas 3 , Eleanor Barnes 4,5 , Niek
de Vries 2 , Ulrich Beuers 1 ; 1 Gastroenterology & Hepatology and
Tytgat Institute of Liver and Intestinal Research, Academic Medical
Center, Amsterdam, Netherlands; 2 Clinical Immunology &
Rheumatology and Amsterdam Rheumatology and Immunology
Center, Academic Medical Center, Amsterdam, Netherlands;
3 Genome Analysis, Academic Medical Center, Amsterdam, Netherlands;
4 Translational Gastroenterology Unit, John Radcliffe Hospital,
Oxford, United Kingdom; 5 NDM Oxford University, Peter
Medawar, Oxford University, Oxford, United Kingdom; 6 Pathology,
Academic Medical Center, Amsterdam, Netherlands; 7 Surgery,
Academic Medical Center, Amsterdam, Netherlands
Introduction: IgG4-associated cholangitis (IAC) and autoimmune
pancreatitis (AIP) are major manifestations of IgG4-related
disease (IgG4-RD). Misdiagnosis and inadequate
treatment are common since IAC and AIP mimic other inflammatory
and malignant pancreatobiliary diseases, and accurate
diagnostic biomarkers are lacking. Moreover, since relapse
after tapering of immunosuppressive therapy occurs in 50%
of patients, there is a need for biomarkers monitoring disease
activity. Recently, using Next-Generation Sequencing,
we observed that dominant IgG4+ B-cell receptor clones in
peripheral blood distinguish patients with active IAC/AIP
from primary sclerosing cholangitis (PSC) and pancreatobiliary
malignancies (CA) [Hepatology 2013;57:2340]. Here,
we report on a simple quantitative PCR (qPCR) protocol for
diagnosing IAC/AIP and monitoring disease activity. Patients
and Methods: 15 patients with IAC and/or AIP according to
HISORt criteria, 7 patients with PSC and 8 with CA formed the
test cohort. Intra- and extramural replication cohorts consisted
of 16 IAC/AIP, 5 PSC and 13 CA patients (Dutch cohort), and
8 IAC/AIP and 8 PSC patients (British cohort). In 20 Dutch
IAC/AIP patients, follow-up samples after 4 and 8 weeks of
corticosteroid therapy were available. RNA was isolated and
the constant region of the B-cell receptor was amplified using a
generic forward IgG primer together with either a generic IgG
or a IgG4-specific reverse primer. The ratio total IgG/IgG4
mRNA was calculated and expressed as ΔC T
. Results: ΔC T
as
measure of IgG/IgG4 mRNA expression in peripheral blood
of the test cohort was 2.8±1.1 (mean+SD) in IAC/AIP patients,
compared to 6.8±1.6 in PSC and 7.6±1.4 in CA (Figure 1A,
p