studies

1272A AASLD ABSTRACTS HEPATOLOGY, October, 2015
2183
Exercise reduces liver fat, visceral fat and circulating
triglycerides, but not inflammatory markers in non-alcoholic
steatohepatitis
David Houghton, Christian Thoma, Kate Hallsworth, Kieren G.
Hollingsworth, Christopher P. Day, Quentin M. Anstee, Michael I.
Trenell; Institute of Cellular Medicine, Newcastle University, Newcastle
Upon Tyne, United Kingdom
Background: Non-alcoholic steatohepatitis (NASH) represents
steatosis and ballooning degeneration, inflammation and fibrosis.
Current treatments for NASH are limited, with no studies
to date reporting the effects of exercise in people with NASH.
Studies in NAFLD show promising effects on liver lipid but the
effect on inflammation and visceral fat, key mediators of fibrosis,
are not known. Aims: Determine the effect of a 12-week
exercise intervention on liver lipid and circulatory inflammation
in people with NASH. Methods: 24 participants (mean age
52 ± 14 years, BMI 33 ± 6) with histologically characterised
NASH (NAFLD Activity Score ≥ 5) received either: exercise
(n = 12) or continue standard care (n = 12) over 12 weeks
and maintained baseline weight. Participants were not undergoing
insulin sensitising treatment, dietary change or regular
activity. Subjects with heart/kidney disease or in vivo ferrous
material were excluded. Liver lipid content, subcutaneous and
visceral adiposity were assessed using magnetic resonance
techniques, inflammation, fibrosis markers, insulin sensitivity
were assessed at baseline and at 12 weeks. Results: Resistance
exercise produced a significant reduction in liver lipid content
(-13 ± 24 vs. 6 ± 16%, P0.05), HOMA
IR (2.3 ± 1.4 to 1.9 ± 0.8 vs. 1.9 ± 1.1 to 1.7 ± 1.1, P>0.05)
or 2hour glucose levels or liver enzymes (ALT: 53 ± 25U/L to
52 ± 18U/L vs. 81 ± 59U/L to 71 ± 52U/L; AST: 41 ± 14U/L
to 45 ± 12U/L vs. 59 ± 41U/L to 58 ± 45U/L, P>0.05). Conclusion:
This is the first study reporting the effects of exercise on
liver lipid, body composition and circulating inflammation in
patients with histologically defined NASH. Exercise produces
a significant reduction in liver lipid, visceral fat and plasma triglycerides
but no effect on body weight, abdominal adiposity,
or circulatory markers of inflammation. These results suggest
that exercise alone may be insufficient to target the mediators
of NASH and warrants further exploration.
Disclosures:
Quentin M. Anstee - Advisory Committees or Review Panels: Genfit, Intercept,
Raptor; Grant/Research Support: GSK; Speaking and Teaching: Abbott Laboratories
The following authors have nothing to disclose: David Houghton, Christian
Thoma, Kate Hallsworth, Kieren G. Hollingsworth, Christopher P. Day, Michael
I. Trenell
2184
The link between intestinal microbiota, bile acids and
non-alcoholic fatty liver disease
Alice Y. Wang 1 , Marialena Mouzaki 2,3 , Bianca M. Arendt 4,5 ,
Robert Bandsma 2,3 , Scott Fung 4,5 , Sandra E. Fischer 4,6 , Johane
P. Allard 4,5 ; 1 Physiology and Experimental Medicine Program,
Research Institute, The Hospital for Sick Children, Toronto, ON,
Canada; 2 Division of Gastroenterology, Hepatology and Nutrition,
The Hospital for Sick Children, Toronto, ON, Canada; 3 University
of Toronto, Toronto, ON, Canada; 4 Toronto General Hospital,
University Health Network, Toronto, ON, Canada; 5 Department of
Medicine, University of Toronto, Toronto, ON, Canada; 6 Department
of Laboratory Medicine and Pathobiology, University of
Toronto, Toronto, ON, Canada
Purpose: Intestinal microbiota (IM) may be implicated in the
pathogenesis of non-alcoholic fatty liver disease (NAFLD)
through their effects on bile acid (BA) homeostasis. To better
elucidate the associations, this study characterizes the fecal
BA profiles of patients with NAFLD and examines the relationship
between IM and fecal BA composition. Methods: This was
a prospective, cross-sectional study. The fecal BA profiles of
adults with biopsy-confirmed NAFLD (non-alcoholic fatty liver:
NAFL and non-alcoholic steatohepatitis: NASH) and healthy
controls (HC) were examined. In a subset of subjects, IM composition
was assessed. Clinical and laboratory data, stool and
blood samples and 7-day food records were collected prior
to liver biopsy. Fecal BAs were quantified by liquid chromatography-tandem
mass spectrometry . Quantitative real-time
polymerase chain reaction was used to measure total bacterial
counts, Bacteroides/Prevotella (Bacteroidetes), C. leptum,
C. coccoides, Bifidobacteria, Escherichia coli and Archaea
in stool. Statistical analyses were conducted using SPSS v.22
(IBM Corp 2013). Results: This study included 53 participants
(25 HC, 11 NAFL, 17 NASH), 56.5% male, with a mean
(±SD) age of 41.0 ± 10.9 years and a median (IQR) BMI of
28.4 (23.4-32.4) kg/m 2 . Total fecal BA levels were higher
in patients with NAFLD (NASH and NAFL combined) compared
to HC (log values: 3.65 and 3.50 pmol/mg, respectively;
p=0.021). The ratio of conjugated to unconjugated BA
was not different between the groups. Patients with NAFLD
had a higher ratio of primary to secondary BA compared to
HC. Levels of unconjugated cholic acid (CA) were higher in
both NASH and NAFL compared to HC (p=0.005, p=0.026,
respectively), whereas chenodeoxycholic acid (CDCA) was
higher in NASH vs. HC (p=0.011). The primary conjugated BA
were not different between the groups; however, patients with
NASH had higher levels of conjugated lithocholic acid (LCA)
than patients with NAFL (p=0.035). In a subset of 29 patients
(18 HC, 11 NAFLD) with IM data, patients with NAFLD had
decreased levels of Bacteroidetes and C. leptum (p=0.041;
p=0. 006), which remained significant after adjusting for BMI
and percent of fat intake. Bacteroidetes levels were inversely
correlated with glycoLCA (r=-0.550, p=0.002) and tauroLCA
(r=-0.408, p=0.048). C. leptum levels were positively correlated
with fecal LCA (r=0.526, p = 0.003) and inversely with
CA (r=-0.669, p