studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 333A
Norah Terrault - Advisory Committees or Review Panels: Eisai, Biotest; Consulting:
BMS, Merck, Achillion; Grant/Research Support: Eisai, Biotest, Vertex,
Gilead, AbbVie, Novartis, Merck
Manal F. Abdelmalek - Consulting: Islet Sciences; Grant/Research Support:
Tobira, Gilead Sciences, NIH/NIDDK, Synageva, Genfit Pharmaceuticals,
Immuron, Galmed, TaiwanJ Pharma, Intercept, NGM Pharmaceuticals
Kris V. Kowdley - Advisory Committees or Review Panels: Achillion, BMS, Evidera,
Gilead, Merck, Novartis, Trio Health, Abbvie; Grant/Research Support:
Evidera, Gilead, Immuron, Intercept, Tobira; Speaking and Teaching: Abbvie,
Gilead
Brent A. Neuschwander-Tetri - Advisory Committees or Review Panels: Nimbus
Therapeutics, Bristol Myers Squibb, Janssen, Mitsubishi Tanabe, Conatus,
Scholar Rock
Reshma Shringarpure - Employment: Intercept
Arun J. Sanyal - Advisory Committees or Review Panels: Bristol Myers, Gilead,
Genfit, Abbott, Ikaria, Exhalenz; Consulting: Salix, Immuron, Exhalenz, Nimbus,
Genentech, Echosens, Takeda, Merck, Enanta, Zafgen, JD Pharma, Islet
Sciences; Grant/Research Support: Salix, Genentech, Intercept, Ikaria, Takeda,
GalMed, Novartis, Gilead, Tobira; Independent Contractor: UpToDate, Elsevier
The following authors have nothing to disclose: Arthur J. McCullough, Saswati
Hazra, Xiaohong Yan, Leigh MacConell
240
Omega-3 fatty acids improve proteomic and lipidomic
markers of endoplasmic reticulum (ER) stress and mitochondrial
dysfunction in a randomized controlled trial in
subjects with Nonalcoholic Steatohepatitis
Livia Rodrigues 1 , Claudia P. Oliveira 1 , José Tadeu Stefano 1 ,
Monize A. Nogueira 1 , Ismael D. Silva 2 , Edson G. Lo Turco 3 ,
Venancio Avancini F. Alves 4 , Flair J. Carrilho 1 , Puneet Puri 5 , Dan
Waitzberg 1 ; 1 Gastroenterology, University of São Paulo School of
Medicine, São Paulo, Brazil; 2 Gynecology, Universidade Federal
de São Paulo, São Paulo, Brazil; 3 Surgery/Urology, Universidade
Federal de São Paulo, São Paulo, Brazil; 4 Patology, University of
São Paulo School of Medicine, São Paulo, Brazil; 5 Gastroenterology,
Hepatology and Nutrition, Virginia Commonwealth University-VCU,
Richmond, VA
Background/Aims: There is no effective FDA approved treatment
for nonalcoholic steatohepatitis (NASH). Increased
n-6/n-3 polyunsaturated fatty acid (PUFA) ratio can induce
endoplasmic reticulum (ER) stress and mitochondrial dysfunction
that characterize NASH. We hypothesized that n-3 PUFA supplementation
would improve these abnormalities. We aimed to
define the hepatic proteomic and plasma lipidomic profiles following
n-3 PUFA therapy in subjects with NASH and relate it to
markers of ER stress and mitochondrial dysfunction. Methods:
A 6-month double blind randomized controlled trial in subjects
with biopsy proven NASH was conducted with n-3 PUFA (945
mg [α linolenic acid/ 64%, eicosapentaenoic acid (EPA)/16%
and docosahexaenoic acid (DHA)/21%]), 3 capsules/day and
matched placebo. A 6-month follow up liver biopsy was performed
per IRB protocol. Hepatic proteomics from formalin-fixed
paraffin embedded liver tissue and plasma lipidomics were
performed at baseline and 6-months in the n-3 PUFA group
using mass spectrometry. The proteins and lipids were matched
to UniProt and LIPID MAPS database respectively. Cytoscape
software was used to analyze functional pathways. Results:
Age and gender matched 60 NASH subjects (n=32, n-3 PUFA
treatment group; n=28, placebo group) completed the study. A
6-month n-3 PUFA therapy significantly (all p 2x baseline and > 5x
ULN, occurring within the first 24 weeks of treatment were
evaluated in context of subsequent clinical outcomes through
Week 48. Results: Overall, 29/172, 25/170, 3/174 and
25/163 patients, respectively, from Arms A-D met criteria for
ALT flare; of those, 18, 16, 2, and 14 patients were baseline
HBeAg-positive. A greater proportion of patients in Arms
A, B and D who experienced ALT flares achieved subsequent
HBeAg loss, HBsAg decline ≥ 1log 10
IU/ml, or HBsAg loss
compared to those who did not experience an ALT flare (table).