studies

1276A AASLD ABSTRACTS HEPATOLOGY, October, 2015
Rajarshi Banerjee - Board Membership: Perspectum Diagnostics; Employment:
Perspectum Diagnostics; Grant/Research Support: Perspectum Diagnostics; Patent
Held/Filed: Perspectum Diagnostics Ltd, University of Oxford; Stock Shareholder:
Perspectum Diagnostics
Elizabeth M. Tunnicliffe - Patent Held/Filed: Perspectum Diagnostics; Stock Shareholder:
Perspectum Diagnostics
Stefan Neubauer - Board Membership: Perspectum Diagnostics; Patent Held/
Filed: University of Oxford
The following authors have nothing to disclose: Jane Collier, Lai Mun Wang,
Fleming A. Kenneth, Jeremy F. Cobbold, Eleanor Barnes
2191
Non-invasive hepatic fibrosis markers and cardiometabolic
risk among adults in the Framingham Heart Study
Michelle T. Long 1,2 , Alison Pedley 2 , Joseph M. Massaro 3,2 , Udo
Hoffmann 4 , Caroline S. Fox 2,5 ; 1 Gastroenterology, Boston Medical
Center, Boston, MA; 2 National Heart, Lung, and Blood Institute’s
Framingham Heart Study, Framingham, MA; 3 Biostatistics, Boston
University School of Public Health, Boston, MA; 4 Radiology,
Massachusetts General Hospital, Boston, MA; 5 Endocrinology,
Brigham and Women’s Hospital, Boston, MA
Background & Aims: Non-alcoholic fatty liver disease (NAFLD)
is associated with an increased risk of cardiovascular related
death, particularly in those with a high predicted risk for hepatic
fibrosis. We determined (a) the prevalence of predicted hepatic
fibrosis based on various non-invasive fibrosis markers and (b)
the association of predicted hepatic fibrosis with cardiovascular
risk factors. Methods: We conducted a cross-sectional
study of 575 Framingham Heart Study participants with NAFLD
based on computed tomography after excluding excess alcohol
use. We estimated the prevalence of predicted hepatic fibrosis
based on the aspartate aminotransferase (AST)/alanine aminotransferase
(ALT) ratio, AST to platelet ratio index (APRI),
and the NAFLD Fibrosis Score (NFS). Using multivariable logistic
regression models, we examined the association between
NAFLD with low, intermediate, or high risk for advanced fibrosis
according to the NFS and various cardiometabolic risk factors.
Results: Among participants with NAFLD, the prevalence
of predicted hepatic fibrosis was 12%, 5%, and 32% based
on the NFS, APRI, and AST/ALT ratio, respectively. Since the
NFS predicted a high risk for advanced fibrosis most similar
to our a priori hypothesis, we continued the analysis using
this model to categorized participants as low, intermediate,
or high risk for advanced fibrosis. In multivariable models,
participants with NAFLD and a high risk for advanced fibrosis
by the NFS had an average 6.87 mm Hg wider pulse pressure
(95% CI 3.33-10.42 mm Hg; p=0.0002) and an increased
odds of hypertension (OR 2.92 95% CI 1.35-6.34; p = 0.007)
compared to those with NAFLD and low risk of fibrosis. There
were no statistically significant differences between the systolic
blood pressure, HDL cholesterol or triglycerides for those
with NAFLD and a high risk of advanced fibrosis by the NFS
compared to those with NAFLD and a low risk of advanced
fibrosis. Conclusions: The AST/ALT ratio, APRI, and NFS give
widely disparate predictions of hepatic fibrosis when applied
to a community-based cohort. Participants with NAFLD and a
high risk for advanced fibrosis based on the NFS had a wider
pulse pressure and increased odds of hypertension. Whether
modifying these risk factors impacts cardiovascular endpoints
in NAFLD patients remains unknown and should be explored
in future studies.
Disclosures:
Alison Pedley - Employment: Merck
The following authors have nothing to disclose: Michelle T. Long, Joseph M.
Massaro, Udo Hoffmann, Caroline S. Fox
2192
Macrophages (CD68+ Cells) and CD8+ T Cytotoxic Cells
are Independently Associated with Advanced Fibrosis in
Patients with Non Alcoholic Fatty Liver Disease (NAFLD)
Azza Karrar 1 , Dinan Abdelatif 2 , Irfan Ali 2 , Yousef Fazel 1 , Pegah
Golabi 1 , Mohamad Houry 1 , Zahra Younoszai 1 , Fanny Monge 2 ,
Munkhzul Otgonsuren 1 , Zachary D. Goodman 2 , Lakshmi Alaparthi
2 , Zobair M. Younossi 1,2 ; 1 Betty and Guy Beatty Center for Integrated
Research, Inova Health System, Falls Church, VA; 2 Center
for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA
Background and Aims: Macrophages (CD68+ cells) and CD8+
T cytotoxic cells dominate the inflammatory infiltrate in NAFLD.
The crosstalk between liver and adipose tissue with regard to
inflammatory cells has not been studied in patients with NAFLD.
We aimed to quantify macrophages and T Helpers cells in liver
and adipose of patients with NAFLD. Methods: Liver biopsy
samples (49) were stained with Hematoxylin and eosin (H&E)
and Masson Trichrome for assessment of NAFLD/NASH and
scored for fibrosis. Digitized images of CD3, CD4, CD8 and
CD68 stained liver and adipose sections were acquired using
The Scan scope XT. An IHC Nuclear Image Analysis algorithm
was used to quantify the percentage of CD3+, CD4+ and
CD8+ cells and a positive pixel count algorithm was used to
quantify the CD68+ cells. Multivariate analysis was performed;
p values ≤ 0.05 were considered to be significant. Results: The
study cohort (N=49) included 33 patients with NASH NAFLD
[Median(IQR) Age=49.00(42.00,55.00); Male=11(33%);
White=25(75.8%); BMI(Kg/m 2 =49.22(40.27,54.67)],
and 16 non NASH NAFLD [Age=45.00(31.00,51.50);
Male=4(25.0%); White=14(87.5%); BMI Kg/
m 2 =44.53(42.23,51.49)]. In univariate analysis, percentages
of CD3+ cells [Odds Ratio (OR): 1.44(1.02, 2.04),
p=0.041], CD8+ cells [OR: 1.29(1.06, 1.58), p=0.011], and
CD68+ cells [OR: 6.39 (1.11, 36.9), p=0.038] in the liver
are significantly associated with higher risk for NASH NAFLD.
Additionally, a greater percentage of CD8+ T cells [OR:
1.33(1.08-1.64), p=0.006] in liver is correlated with higher
risk for pericellular fibrosis, while in adipose, a greater percentage
of CD3+ cells [OR: 0.67 (0.49-0.92), p=0.012] and
CD8+ cells [OR: 0.78 (0.60-1.01), p=0.058] are correlated
with lower risk of pericellular fibrosis. In liver, it is also found
that a greater percentage of CD8+ cells [OR: 1.33(1.10-1.59),
p=0.002] and CD68+ cells [OR: 5.87(1.38-25.1), p=0.017]
are associated with higher risk of advanced fibrosis. In multivariate
analysis, in the liver, a greater percentage of CD8+
cells [OR: 1.28 (1.04-1.58), p=0.020) are independently
associated with higher risk for pericellular fibrosis and greater
percentage of CD68+ cells [OR: 7.37 (1.58-34.4), p=0.011]
are independently associated with higher risk of advanced
fibrosis. Conclusion: We show that CD8+ T cells are strongly
associated with pericellular fibrosis while CD68+ cells are
strongly associated with advanced fibrosis. Therefore macrophages
and CD8+ cells are key cells in NAFLD progression.
Disclosures:
Zachary D. Goodman - Consulting: Gilead Sciences, Abbvie; Grant/Research
Support: Gilead Sciences, Fibrogen, Galectin Therapeutics, Intercept, Synageva,
Conatus, Tobira, Exalenz
Zobair M. Younossi - Advisory Committees or Review Panels: Salix, Janssen,
Vertex; Consulting: Gilead, Enterome, Coneatus
The following authors have nothing to disclose: Azza Karrar, Dinan Abdelatif,
Irfan Ali, Yousef Fazel, Pegah Golabi, Mohamad Houry, Zahra Younoszai,
Fanny Monge, Munkhzul Otgonsuren, Lakshmi Alaparthi