studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 1257A
length appears to be an important factor impacting histological
assessments and has important implications for the interpretation
of placebo-controlled trials in NASH. Shorter biopsy
length can increase placebo response in a trial and therefore,
biopsy length should be closely monitored and factored into
sample-size assessment.
Disclosures:
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
Norah Terrault - Advisory Committees or Review Panels: Eisai, Biotest; Consulting:
BMS, Merck, Achillion; Grant/Research Support: Eisai, Biotest, Vertex,
Gilead, AbbVie, Novartis, Merck
Brent A. Neuschwander-Tetri - Advisory Committees or Review Panels: Nimbus
Therapeutics, Bristol Myers Squibb, Janssen, Mitsubishi Tanabe, Conatus,
Scholar Rock
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
Rohit Loomba - Advisory Committees or Review Panels: Galmed Inc, Tobira Inc,
Arrowhead Research Inc; Consulting: Gilead Inc, Corgenix Inc, Janssen and
Janssen Inc, Zafgen Inc, Celgene Inc, Alnylam Inc, Inanta Inc, Deutrx Inc; Grant/
Research Support: Daiichi Sankyo Inc, AGA, Merck Inc, Promedior Inc, Kinemed
Inc, Immuron Inc, Adheron Inc
Reshma Shringarpure - Employment: Intercept
David Shapiro - Employment: Inttercept Pharmaceuticals; Management Position:
Intercept Pharmaceuticals; Stock Shareholder: Intercept Pharmaceuticals
The following authors have nothing to disclose: Xiaohong Yan, Arthur J.
McCullough
2154
Predictors of improvement in NAFLD Activity Score to
obeticholic acid: A secondary analysis of FLINT Trial
Rohit Loomba 1 , Arun J. Sanyal 2 , Kris V. Kowdley 3 , Norah Terrault
4 , Naga P. Chalasani 5 , Manal F. Abdelmalek 6 , Arthur J.
McCullough 7 , Xiaohong Yan 8 , Reshma Shringarpure 8 , Beatrice
Ferguson 8 , David Shapiro 8 , Brent A. Neuschwander-Tetri 9 ; 1 University
of California, San Diego, La Jolla, CA; 2 Virginia Commonwealth
University, Richmond, VA; 3 Swedish Medical Center,
Seattle, WA; 4 University of California, San Francisco, San Francisco,
CA; 5 Indiana University, Indianapolis, IN; 6 Duke University,
Durham, NC; 7 Cleveland Clinic, Cleveland, OH; 8 Intercept
Pharmaceuticals, San Diego, CA; 9 Saint Louis University Health
Sciences Center, St. Louis, MO
Background: The Farnesoid X Receptor (FXR) Ligand Obeticholic
Acid (OCA) in NASH Treatment (FLINT) Trial showed
that OCA led to significantly higher rates of histologic response
(defined as an improvement in NAFLD activity score [NAS] by
≥2 with no worsening of fibrosis). Aim: The aims of this secondary
analysis of the FLINT trial was to identify predictors of histologic
response after 72 weeks of OCA treatment. Methods:
Logistic regression model with stepwise selection procedure
was performed to identify potential predictors of response after
72 weeks of OCA treatment. Model selection was based on
Akaike information criterion (AIC) and Bayesian information
criterion (BIC). All patients included in analysis had biopsies
at baseline (BL) and 72 weeks. Predictor data collected at BL,
weeks 12, 24, and 36 were evaluated in this model. 59 predictors
were assessed including BL values for demographics,
histology, liver and serum biochemistry as well as the changes
in those parameters over the course of the trial. The selected
parameters were used to build a predictive model in OCAtreated
patients for predicting response defined as improvement
in the NAS by ≥2 with no worsening of fibrosis. The model was
cross-validated by jackknife method, area under the receiver
operating characteristic curve (AUROC), and 95% CIs. Results:
Among 102 OCA-treated patients, 50 (49%) showed ≥2 point
improvement in NAS without worsening fibrosis. This predictive
model showed that older age, higher BL NAS, lower BL BMI,
higher BL uric acid, and decrease in AST at week 24, increase
in creatinine at week 24 and greater weight loss at week 24
was associated with histologic response on OCA treatment
(Table). The predictive model for placebo-treated patients was
distinct from the OCA-treated patients (not shown). Conclusions:
Baseline characteristics and changes in clinical parameters
may be helpful in predicting histological response to OCA
therapy in adults with NASH and further evaluation with larger
patient numbers is warranted.
Disclosures:
Rohit Loomba - Advisory Committees or Review Panels: Galmed Inc, Tobira Inc,
Arrowhead Research Inc; Consulting: Gilead Inc, Corgenix Inc, Janssen and
Janssen Inc, Zafgen Inc, Celgene Inc, Alnylam Inc, Inanta Inc, Deutrx Inc; Grant/
Research Support: Daiichi Sankyo Inc, AGA, Merck Inc, Promedior Inc, Kinemed
Inc, Immuron Inc, Adheron Inc
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
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
Norah Terrault - Advisory Committees or Review Panels: Eisai, Biotest; Consulting:
BMS, Merck, Achillion; Grant/Research Support: Eisai, Biotest, Vertex,
Gilead, AbbVie, Novartis, Merck
Naga P. Chalasani - Consulting: Abbvie, Lilly, Celgene, Tobira, NuSirt, Takeda,
Merck/Anthem, Salix; Grant/Research Support: Intercept, Gilead, Galectin
Manal F. Abdelmalek - Consulting: Islet Sciences; Grant/Research Support:
Tobira, Gilead Sciences, NIH/NIDDK, Synageva, Genfit Pharmaceuticals,
Immuron, Galmed, TaiwanJ Pharma, Intercept, NGM Pharmaceuticals
Reshma Shringarpure - Employment: Intercept
Beatrice Ferguson - Employment: Intercept Pharmaceuticals
David Shapiro - Employment: Inttercept Pharmaceuticals; Management Position:
Intercept Pharmaceuticals; Stock Shareholder: Intercept Pharmaceuticals
Brent A. Neuschwander-Tetri - Advisory Committees or Review Panels: Nimbus
Therapeutics, Bristol Myers Squibb, Janssen, Mitsubishi Tanabe, Conatus,
Scholar Rock
The following authors have nothing to disclose: Arthur J. McCullough, Xiaohong
Yan