studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 1269A
ALT from randomisation to the end of treatment in the metronidazole
and inulin treatment arm (Group 3) compared to
the placebo group (group 1), (mean change in ALT -18.6 vs
-0.5 U/L respectively; p=0.04). The reduction in ALT in group
2 was not significantly different to the placebo group (mean
change ALT -2.6 vs 0.5U/L respectively; p=0.5). At the end of
treatment reduction in BMI, fasting lipids, glycaemia, BP and
Fibroscan ® CAP scores did not significantly differ between the
three groups. Conclusions: This is the first clinical trial evidence
that supplementation with prebiotic inulin following brief metronidazole
therapy can further reduce liver aminotransferase
after 4 weeks VLCD therapy in patients with NAFLD. This is a
potentially viable clinical therapy which requires validation in
larger clinical studies of longer duration.
Disclosures:
The following authors have nothing to disclose: David W. Orr, Rinki Murphy
2177
Diagnostic accuracy for non-alcoholic fatty liver disease
(NAFLD) with controlled attenuation parameter (CAP)
measured by transient elastography
Masahiro Kikuchi 1,2 , Rumiko Umeda 2 , Kota Tsuruya 2 , Hirokazu
Shiozawa 2 , Miho Kikuchi 1 , Masahiko Takahashi 1 , Yoshinori
Horie 4 , Yasuhiro Nishizaki 3 ; 1 Gastroenterology, National Hospital
Organization Tokyo Medical Center, Tokyo, Japan; 2 Gastroenterology,
Tokai University Tokyo Hospital, Tokyo, Japan; 3 Life Care
Center, Tokai University Tokyo Hospital, Tokyo, Japan; 4 International
University of Health and Welfare, Research Centre of Clinical
Medicine, Sanno Medical Center, Tokyo, Japan
Purpose: We reported that pulse wave velocity (PWV) as arteriosclerosis
index accelerate and remnant like particles cholesterol
(RLP-C), triglyceride (TG), and free fatty acid (FFA) which
are arteriosclerosis promoting factors increase in non-alcoholic
fatty liver disease (NAFLD). As NAFLD is closely related to
cardiovascular deaths, a detection of the early stage of NAFLD
patient is important. In this study, we aimed to investigate the
diagnostic performance of controlled attenuation parameter
(CAP) based on FibroScan ® 502 (Echosens,France) in NAFLD
patients. Method: 341 non-viral hepatitis patients who intake
alcohol less than 20g ethanol per day were enrolled. The
existence of the fatty liver was assessed by B-mode ultrasonography,
and it divided into two groups. (male: NAFLD (+)
126cases and NAFLD (-) 97cases, female: NAFLD (+) 34cases
and NAFLD (-) 84cases), and CAP was performed simultaneously.
Moreover, fatty liver index (FLI) (Bedogni G.2006),
hepatic steatosis index (HSI) (Lee JH.2010) and lipid accumulation
product (LAP) (Chinag Jui-Kun.2012) known as liver steatosis
prediction formulas from various physical measurements
and multiple blood markers were investigated, and we compared
the usefulness for detecting NAFLD with ROC analysis.
Result: CAP value, FLI, HSI, and LAP were significantly high in
the NAFLD (+) group compared with the (-) group (P< 0.0001).
In male the area under ROC curve (AUROC) for NAFLD diagnostic
tool was CAP: 0.890, FLI: 0.779, HSI: 0.811, and LAP:
0.718 respectively. In female it was CAP: 0.894, FLI: 0.939,
HSI: 0.911, and LAP: 0.928. The CAP was correlated with
diagnosis of NAFLD especially in male (cut-off value=257d-
B/m, sensitivity=87%, specificity=79%). Conclusion: The utility
of CAP value was verified as accurate diagnosis tool for
NAFLD. The detection of CAP value would influence the more
aggressive treatment intervention and the raised motivations of
therapy for NAFLD patients. This instrument must be contributed
to not only the detection of NAFLD but also the prevention of
arteriosclerosis related cardiovascular deaths.
Disclosures:
The following authors have nothing to disclose: Masahiro Kikuchi, Rumiko
Umeda, Kota Tsuruya, Hirokazu Shiozawa, Miho Kikuchi, Masahiko Takahashi,
Yoshinori Horie, Yasuhiro Nishizaki
2178
DACRAs are novel therapeutic candidates for the treatment
of NAFLD and NASH
Mette J. Nielsen 1,2 , Sara T. Hjuler 1 , Sofie Gydesen 1 , Morten A.
Karsdal 1 , Kim Henriksen 1 ; 1 Nordic Bioscience A/S, Herlev, Denmark;
2 Department of Gastroenterology and Hepatology, Odense
University Hospital, University of Southern Denmark, Odense, Denmark
Background and aim: Nonalcoholic fatty liver disease (NAFLD)
is a significant complication of obesity and in many cases
it leads to the development of nonalcoholic steatohepatitis
(NASH). NAFLD is defined by the presence of liver fat accumulation
exceeding 5% of hepatocytes and is strongly associated
with the metabolic syndrome. While weight loss is beneficial,
there are no pharmacological treatments for NAFLD and
NASH, and novel candidates are intensely sought. DACRAs
(dual amylin and calcitonin receptor agonists) are novel peptide-based
drug candidates, which have shown promise in the
treatment of type 2 diabetes due to potent weight reduction
and alleviation of insulin resistance. Methods: In this study, we
used High-Fat Diet (HFD)-induced obese Sprague-Dawley rats
treated with different doses (0.625-10mg/kg) the DACRA KBP-
042 for 8 weeks to elucidate the effects of a novel DACRA on
liver fat accumulation, body weight, insulin/glucagon balance
and glucose homeostasis. Results: A dose-dependent and sustained
weight loss was obtained, resulting in a 4.7 % weight
reduction (20 % vehicle-corrected) in the KBP-042 10 mg/kg
group with a transient reduction in food intake. The weight
loss was clearly superior to calorie-matched groups. Corresponding
with the weight loss, visceral fat depots were significantly
reduced (perirenal Adipose Tissue (AT): p