Digestive and Liver Disease - Volume 48 - Supplement 2

Abstracts of the 22

National Congress of Digestive Diseases / Digestive and Liver Disease 48S2 (2016) e67–e231

e117

shortening length during incomplete TLESRs and wet swallows was

1.5 ± 0.31 cm and 0.8 ± 0.14 cm in patients, and 0.9 ± 0.14 cm (p<0.05)

and 0.6 ± 0.15 cm. (p: ns) in HVs. Increases of esophageal pressure

during incomplete TLESRs were of 4.2 ± 0.4 mmHg in patients and

3.8 ± 0.2 mmHg in HVs (p: ns). A linear direct correlation between

intra-esophageal pressure increases and length of LES lifts was

found (R 0.76, p<0.05).

Conclusions:

Shortening can be clearly appreciated during incom

plete TLESRs and wet swallows. In contrast to swallow-induced

LES relaxation, the degree of esophageal shortening during an

incomplete TLESR is more pronounced. EGJ might be an initial

event contributing to LES opening and a key factor involved in GERD

pathogenesis.

OC.12.6

THE ROLE OF S100B IN THE DEVELOPING ENTERIC NERVOUS

SYSTEM

Capoccia E.*

, Esposito G.

, Vanden Berghe P.

Department of Physiology and Pharmacology, Sapienza University

Vittorio Erspamer, Roma, Italy,

Laboratory for Enteric Neuroscience

(LENS), TARGID, University of Leuven, Leuven, Belgium

Background and aim:

S100B is a Ca2+ binding protein, which is

predominantly produced by glial cells. Previous studies have shown

that S100B is first expressed at embryonic day (E)14.5 by post-

mitotic enteric glial cells. However, currently little is known about

its possible function and whether the specific onset of expression

is important for the developing the enteric nervous system (ENS).

Material and methods:

We cultured intact E13.5 gut in the

presence of arundic acid (300 μM), an inhibitor of S100B protein

synthesis, for 2 days in vitro. We then analysed changes in the

numbers of enteric neurons, glia and ENS progenitors by performing

immunohistochemistry against HuC/D, S100B and Sox10.

Results:

In control cultures, S100B expression was identified

in the rostral small intestine. This expression was successfully

inhibited by arundic acid. Exposure to arundic acid did not affect the

number of HuC/D+ neurons but significantly reduced the number

of Sox10+ cells. The remaining Sox10+ cells also showed weaker

immunoreactivity. Surprisingly, a subpopulation of HuC/D+ cells

also exhibited Sox10-immunoreactivity in their nucleus. This was

observed only in arundic acid cultures, but not in control conditions.

Conclusions:

Our data suggest that the timely appearance of S100B

is important for the development of the ENS. Inhibition of the onset

of S100B expression could redirect fate specification of neurons and

glia. We are currently investigating the identity of the HuC/D and

Sox10 co-expressing cells that appear as a result of inhibition of

S100B expression.

OC.12.7

BILE DUCT INVOLVEMENT IN AUTOIMMUNE PANCREATITIS:

CLINICAL FEATURES AND PROGNOSTIC ASPECTS IN 92 PATIENTS

Campagnola P.*, Amodio A., Conti Bellocchi M.C., Capuano F.,

Vettori G., Perini C., Moser L., Gabbrielli A., Frulloni L.

Gastroenterologia AOUI Verona Dept Medicine, Verona, Italy

Background and aim:

Autoimmune pancreatitis (AIP) is a peculiar

form of pancreatitis classified in type 1, type 2 and type NOS by

International Consensus Diagnostic Criteria (ICDC). Disease relapse

can be observed in up to 50% of patients, more frequently in type 1

and NOS AIP. Risk factors for recurrences are IgG4 serum levels and

extra-pancreatic involvement, particularly intra-hepatic.

Aim of the study was to evaluate the bile duct involvement as

prognostic factor for recurrences and the relationship between

intra-hepatic bile duct involvement, IgG4 serum levels and extra-

pancreatic involvement.

Material and methods:

We enrolled AIP patients observed in our

center in the period 2009-2014. AIP was diagnosed according to

ICDC. We evaluated MRI/MRCP to evaluate the biliary involvement,

classified in normal (N), intra-hepatic±extraepatic (IE), and only

extra-hepatic (EE). Exclusion criteria were patients who underwent

surgery (pancreatic or biliary) or patients without imaging at clinical

onset.

Results:

A total of 92 patients (70 males, 22 females, median age

48.7 ± 17.9 years) were included, 51 (55%) in N group, 21 (23%) in IE,

and 20 (22%) in EE. IE patients are older (p=0.017), suffering more

frequently from type 1 AIP (p=0.003), with kidney involvement

(p=0.004). IgG4 serum levels are higher in IE (688.6 ± 678.4 mg/

dl) than in EE and N (290.3 ± 319.3 mg/dl)(p=0.005). Patients with

intrahepatic bile duct involvements relapse more frequently in

comparison with others groups but the difference did not reach the

statistical significance (p=ns).

Conclusions:

AIP with intra-hepatic involvement is a more

aggressive disease and, probably, a manifestation of IgG4-related

systemic disease.

OC.12.8

LONG-TERM SAFETY OF OBETICHOLIC ACID IN PATIENTS WITH

PRIMARY BILIARY CIRRHOSIS

Peters Y.

, Hooshmand-rad R.

, Pencek R.

, Owens-grillo J.

Marmon T.

, Macconell L.

, Picaro L.A.

, Adorini L.*

, Shapiro D.

Intercept Pharmaceuticals Inc, S. Diego, California, United States,

Intercept Pharmaceuticals LTD Europe, London, United Kingdom

Background and aim:

Obeticholic Acid (OCA) is a potent and

selective farnesoid X receptor (FXR) agonist developed for treatment

of primary biliary cirrhosis (PBC). 216 patients with PBC were treated

in a randomized, double blind (DB), placebo (PBO) controlled Phase 3

clinical study to evaluate the efficacy and safety of OCA. 198 patients

completed the DB phase of the study and 193 enrolled in a long term

safety extension (LTSE) phase. Exposure to OCA during the DB phase

resulted in statistically significant liver biochemistry improvements

and was generally well tolerated.

Material and methods:

All patients enrolled in the LTSE first met

the inclusion criteria for the DB study, which included PBC diagnosis,

ALP ≥1.67x ULN and/or total bilirubin >ULN to <2x ULN, stable UDCA

or unable to tolerate UDCA. During the DB phase, patients were

randomized to placebo, OCA 5 mg titrating to 10 mg after 6 months

based on tolerability/clinical response, or OCA 10 mg. In the LTSE,

all patients started at OCA 5 mg with the option to increase by 5 mg

every 3 months. An interim safety analysis was conducted after the

initial 12 month LTSE period.

Results:

Long-term OCA treatment demonstrated durability of

therapeutic response and safety out to 2 years; no new safety signals

emerged during the LTSE. The overall incidence of new adverse

events (AEs) during the LTSE was lower for patients who received

OCA during the DB phase, suggesting improved tolerability. Pruritus

was the most common AE. As with the overall AE rate, the incidence

of new pruritus was lower during the LTSE phase (DB: 56% OCA

titration, 68% OCA 10 mg; LTSE: 15% OCA 5 mg, 21% OCA 10 mg). The

use of an OCA titration strategy improved study retention; 0% PBO,

1% OCA titration, and 10% OCA 10 mg discontinued due to pruritus

in the DB phase and <1% patients withdrew due to pruritus in the

LTSE. After 2 years of OCA treatment, LDL remained comparable

to baseline while the decrease observed in HDL during the DB

remained unchanged in the LTSE. During the LTSE, the overall SAE

incidence was low (9% OCA 5 mg, 7% OCA 10 mg), none were related

to OCA and there continued to be no trend in the types of SAEs that

were observed.