studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 1069A
CK19, and γH2AX and p21 expression verified DNA damage
and related perturbations with incomplete liver regeneration.
Phosphoprotein analysis of differences in injured versus healthy
livers using normalization with housekeeping gene products
and >2-fold up- or downregulated phospho- versus total proteins
indicated abnormalities in ATM signaling pathways
(e.g., ATM, Chek2, CDKN1a, CDNK1b, E2F1, Gadd45,
Rad51, p53, p73), cell cycle regulators (e.g.,CCNB1, CCNC,
CCND3, CCNE1, CDC25c, Cdk1, Cdk2, Cdk, Cdk7) besides
cell stress, inflammation, etc. IPA mapping of these and other
proteins indicated dysregulations in DNA damage/ repair and
G0/G1 and G2/M checkpoint controls. In cultured HuH-7
cells, APAP cytotoxicity reproduced double-strand DNA breaks,
dysregulation in ATM signaling and G0/G1 and G2/M checkpoint
restrictions. Conclusions: APAP-induced ALF in human livers
was characterized by replicative stress and arrest of cells in
G0/G1 due to DNA damage with dysregulated ATM signaling
and cell cycle checkpoint controls. These molecular alterations
offer therapeutic targets for drug development with or without
cell therapy to restore liver regeneration in ALF.
Disclosures:
The following authors have nothing to disclose: Preeti Viswanathan, Yogeshwar
Sharma, Sriram Bandi, Sanjeev Gupta
The baseline characteristics of all paracenteses episodes before
and after propensity score matching
Disclosures:
The following authors have nothing to disclose: Su Lin
1765
Lower fibrinogen level predicts hemorrhagic complications
following abdominal paracentesis in patients
with acute-on-chronic liver failure: A propensity score
analysis
Su Lin; Liver Research Center of the First Affiliated Hospital of
Fujian Medical University, Fuzhou, China
Object Patients with acute on chronic liver failure (ACLF) usually
present severe coagulopathy. Abdominal paracentesis is
often performed in those patients. The aim of this study was to
analyze the prevalence of hemorrhagic events after abdominal
paracentesis and the predictive factors of it in ACLF populations.
Methods Patients who were diagnosed as ACLF from
1 January 2010 to 31 December 2014 were enrolled. Those
who had any signs of ascites underwent routine paracentesis
upon and after admission. A propensity score matching
analysis (greedy nearest neighbor matching) was used to
select matched cases from overall non-hemorrhagic group as
a control group. Hemorrhagic complications and the risk factors
were examined using bilinear logistic regression analysis.
Results A total of 602 abdominal paracenteses were carried
out on 218 ACLF patients within a 5-year period. A total of
18 (2.99%) hemorrhagic complications were identified, with
4 cases of abdominal wall hematomas and 14 cases of intraperitoneal
hemorrhage. We finally matched 18 cases with
bleeding events to 72 unique cases without bleeding cases.
The patients with hemorrhagic events had significantly lower
fibrinogen levels and higher PT level than non-hemorrhagic
ones. Bilinear regression revealed that lower fibrinogen level
could independently predict hemorrhagic complication (OR:
0.128, 95% CI 0.023-0.697, p = 0.017). The best cut-off
value of fibrinogen level f>or predicting bleeding events>was 0.70 g/L,
with the sensitivity of 76.4% and specificity of 80.0%. The area
under curve was 0.733 (95% CI 0.604-0.862, P =0.002).
Conclusion Severe hemorrhagic complications happened in
2.99% of all paracenteses performed for ACLF patients. Low
fibrinogen level (≤0.70g/L) is an independent predictor.
1766
Does weight loss surgery predispose to acetaminophen-related
acute liver failure?
Shannan Tujios 2 , Michelle Gottfried 1 , Valerie L. Durkalski 1 , William
M. Lee 2 ; 1 Medical University of South Carolina, Charleston,
SC; 2 University of Texas Southwestern, Dallas, TX
Background: Obesity and bariatric surgery are increasingly
common with nearly 180,000 Americans undergoing weight
loss surgery (WLS) annually; an estimated 4.5 million individuals
in the United States have had bariatric surgery to date. A
previous study (J Clin Gastro 2014 epub) suggested that prior
WLS was over-represented among patients with acetaminophen
(APAP) related acute liver injury or acute liver failure
(ALI/ALF). Aims: To describe the presentation, etiology and
outcome of ALI/ALF patients with prior WLS, compared to a
large group of ALF patients with acetaminophen (APAP) overdose
without prior WLS. Methods: 57 patients with prior WLS
enrolled in the US ALFSG registry between 01/1998 and
04/2015 were reviewed and compared to 1234 remaining
non-WLS APAP patients. Results: During the early study era
(1998-2009), 1.5% of all cases (N=1678) reported prior WLS,
while 3.2% of all cases since (2010-2015) (N=997) had prior
WLS. Those with prior WLS were largely female (96.5%), and
white (84.2%), and most demonstrated advanced coma grades
(3-4; 75%) during hospitalization; 43 (75.4%) were APAP-related,
3 (5.3%) due to idiosyncratic drug injury and 4 (7%)
indeterminate. Nearly 25% of WLS APAP patients were listed
for liver transplant with 9 patients (64% of those) receiving a
graft; 21 day spontaneous survival was 58.5%, compared to
unadjusted overall survival of 61.4%. Comparing the cohort
of 43 APAP patients with prior WLS to the remaining APAP
patients, there were no differences in age, race or reported
alcohol use. The WLS group was more often female (95.4% vs
73.7%, p=0.0014), and was more anemic (median hemoglobin
9.5 gm/dL vs 11.2 gm/dL p=