studies

656A AASLD ABSTRACTS HEPATOLOGY, October, 2015
The following authors have nothing to disclose: Yuan-Ping Han, Danmei Su,
Yuanyang Nie, Airu Zhu, Zishuo Chen, Li Zhang, Pengfei Wu, Mei Luo, Guihui
Wu, Richard Hu, Aurelia Lugea, Jun Xu, Hidekazu Tsukamoto
905
Fecal Alkaline Phosphatase Is a Determinant Of Metabolic
Endotoxemia And Severity Of Nonalcoholic Fatty
Liver Disease (NAFLD)
Kalyani Daita 1 , Lorenzo Mulazzani 2 , Robert Vincent 1 , Amon
Asgharpour 1 , Sophie C. Cazanave 1 , Mohammad S. Siddiqui 1 ,
Puneet Puri 1 , Michael Idowu 1 , Sherry L. Boyett 1 , Faridoddin Mirshahi
1 , Hae-Ki Min 1 , Robert E. Brown 3 , Masoumeh Sikaroodi 3 ,
Patrick M. Gillevet 3 , Arun J. Sanyal 1 ; 1 VCU, Richmond, VA; 2 Università
di Bologna, Bologna, Italy; 3 George mason university,
Manassas, VA
BACKGROUND: Endotoxemia plays a key role in the genesis of
insulin resistance (IR) and activation of the innate immune system
(IAS) in the metabolic syndrome (Nature 2012; 485:S12).
IR and activation of the IAS are important in the pathogenesis
of NAFLD. Alkaline phosphatase (AP) dephosphorylates
endotoxin (ET) and renders it inactive and intestinal AP (IAP)
is critical to limit ET exposure (AmJPath151.4;1997,1163).
HYPOTHESIS: We hypothesized that fecal IAP (F-IAP) activity
would be inversely related to severity of endotoxemia and the
severity of underlying NAFLD. AIMS: (1) to determine if NASH
was associated with lower fecal IAP and higher endotoxin levels
compared to controls and NAFL, (2) to determine the relationship
between fecal IAP and plasma ET and liver histology
across the spectrum of NAFLD, (3) to determine if changes in
fecal IAP were linked to intestinal inflammation as assessed by
fecal calprotectin, and (4) to identify changes in the intestinal
microbiome associated with altered fecal IAP. METHODS: Subjects
with nonalcoholic fatty liver (NAFL, n= 9) or nonalcoholic
steatohepatitis (NASH, n=15) were compared to 5 weight
matched controls. Fecal IAP was measured by chromogenic
quantification with Dako 5-bromo-4-chloro-3-indoyl-phosphate/
nitroblue with calf AP as an internal control. Plasma ET and
fecal calprotectin were measured by a chromogenic quantification
kit and ELISA respectively. Liver histology was scored
according to NASH CRN criteria. Stool microbiome was analyzed
using 16s pyrosequencing. RESULTS: F-IAP was significantly
lower in NASH compared to NAFL as well as controls
(237.13 U/mg dry weight vs 306.03 and 314.2, p< 0.01
and 0.03 respectively). The plasma AP was similar between
groups. NASH was associated with higher endotoxemia than
both NAFL and controls (1.53 EU/ml vs 1.3 and 1.26, p<
0.02 and 0.03 respectively). There was a tight inverse relationship
between F-IAP and ET levels (r=-0.42, p