studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 1295A
2231
High prevalence of undiagnosed liver cirrhosis and
advanced fibrosis in type 2 diabetic outpatients
Francisco Barrera, Juan P. Arab, Carlos E. Benítez, Arnoldo
Riquelme, Marco Arrese; Department of Gastroenterology, Escuela
de Medicina, Pontificia Universidad Catolica de Chile, Santiago,
Chile
BACKGROUND: Patients with Type 2 Diabetes Mellitus (T2DM)
are at risk for developing end-stage liver disease due to nonalcoholic
steatohepatitis (NASH). Non-invasive methods have
been validated for assessing the severity of nonalcoholic fatty
liver disease (NAFLD). Data on prevalence of advanced fibrosis
among T2DM patients evaluated by these methods is scarce.
AIM: To evaluate prevalence of steatosis, advanced fibrosis
and cirrhosis by non-invasive methods in T2DM patients.
METHODS: We conducted a cross-sectional study in 145 consecutive
T2DM patients (>55 years-old). The presence of cirrhosis
and advanced fibrosis was evaluated by liver morphology
assessed by magnetic resonance imaging (MRI) and NAFLD
fibrosis score (NFS) respectively. Exclusion criteria included
significant alcohol consumption, viral hepatitis or other liver
diseases and exposure to hepatotoxic agents. RESULTS: 52.6%
were women, average age was 60 years (57-64), BMI was
29.6±4.7 kg/m 2 and diabetes duration was 7.6±6.9 years.
A high prevalence of liver steatosis (62.4%) and steatosis
and abnormal ALT (37.6%) was found. The prevalence of
advanced fibrosis using the NFS was 12.8 and evidence of
liver cirrhosis on MRI was 5.3%. In a multivariate analysis GGT
>82 IU/L (P=0.004) and no alcohol intake (P=0.032) were
independently associated to advanced fibrosis. CONCLUSION:
A high frequency of undiagnosed advanced fibrosis and cirrhosis
was observed in otherwise unselected T2DM patients older
than 55 y/o. These patients are at high risk of developing liver-related
complications such as portal hypertension and hepatocellular
carcinoma. Routine screening for liver disease should
be considered in this population (Grant Support: FONDECYT
1150327 to M.A.and 1150311 to F.B) .
Disclosures:
The following authors have nothing to disclose: Francisco Barrera, Juan P. Arab,
Carlos E. Benítez, Arnoldo Riquelme, Marco Arrese
2232
Discovery of plasma biomarkers for NAFLD using high
resolution metabolomics
Miriam B. Vos, Ran Jin, Sophia Banton, Shuzhao Li, Dean P. Jones;
Emory University, Atlanta, GA
Purpose: Past attempts to develop diagnostic tests for NAFLD
using single metabolite biomarkers have failed in part because
of the heterogeneity of NAFLD. High throughput, high resolution
metabolomics is rapid and relatively inexpensive, making it a
promising platform for disease identification and characterization.
Methods: We performed an exploratory, unbiased metabolomics
pilot study to develop a biomarker panel for detecting
NAFLD. Fasting plasma samples of 39 Hispanic-American adolescents
with either MRS-documented NAFLD (intrahepatic fat >
5%) or age and BMI matched control individuals (intrahepatic
fat < 5%) were analyzed using LC-MS high-resolution metabolomics.
A total of 9,583 metabolite features were yielded
initially. The top discriminatory and identifiable metabolites
were selected. Multivariate receiver operating characteristic
(ROC) curves were generated for individual metabolites and
combinations of metabolites, respectively. Results: Univariate
ROC curves >0.80 were observed with 7 of the top metabolites,
which included metabolites from de novo lipogenesis,
ketogenic amino acids and hormones. Multivariate ROC analysis
with cross validation using balanced subsampling demonstrated
that combinations of the top 7, 10, and 16 selected
metabolites had higher prediction for NAFLD (AUC>0.9 for all
panels, Figure 1) compared to single metabolites. Conclusions:
This pilot “omics”-based biomarker development study shows
feasibility in using a metabolomics based biomarker panel to
identify NAFLD with high sensitivity and specificity. Independent
validation studies are warranted to confirm clinical utility.
Disclosures:
The following authors have nothing to disclose: Miriam B. Vos, Ran Jin, Sophia
Banton, Shuzhao Li, Dean P. Jones
2233
Polychlorinated biphenyl exposure in Anniston, Alabama
is associated with elevated prevalence of liver
disease
Heather B. Clair 1 , Keith C. Falkner 1 , Russell A. Prough 2 , Christina
Pinkston 1 , Guy N. Brock 1 , Marian Pavuk 3 , N. Dutton 3 , Matthew
C. Cave 1,4 ; 1 Department of Medicine/GI, University of Louisville,
Louisville, KY; 2 Biochemistry, University of Louisville, Louisville, KY;
3 CDC, Atlanta, GA; 4 Robley Rex VAMC, Louisville, KY
Purpose: Elevated serum concentrations of Polychlorinated
Biphenyls (PCBs) are associated with increased liver injury
in the general US population. Residents of Anniston, AL are
highly exposed to PCBs, resulting in a mean serum PCB concentrations
3-4 times the mean of the general US population.
An adult cohort of Anniston residents (Anniston Community
Health Survey – ACHS) was assembled to study health effects
and PCB exposure. We report elevated liver injury biomarkers
characteristic of Toxicant-Associated Steatohepatitis (TASH),
cytokine and adipokine abnormalities. A resampling of this
population provided longitudinal data related to liver disease,
metabolic abnormalities and total PCB load, as well as an
expanded analysis of the dioxin-like PCB congener concentration
in Anniston residents. Methods: Subjects were recruited
from residences within the city limits of Anniston, Alabama.
Serum samples from 738 of the individuals recruited in 2005-
2007 (ACHS1), and 352 individuals re-sampled in 2014
(ACHS2) were included in our analysis. In both groups, whole
(CK18 M65) and caspase-cleaved cytokeratin 18 (CK18 M30)
were measured using the PEVIVA ELISAs. Serum cytokine/