studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 1221A
2077
The NDP52 Val248Ala variant increases the risk for
spontaneous bacterial peritonitis in patients with alcoholic
liver cirrhosis.
Philipp Lutz 1,2 , Benjamin Krämer 1,2 , Dominik J. Kaczmarek 1,2 ,
Marc P. Hübner 3,2 , Bettina Langhans 1,2 , Beate Appenrodt 4 , Frank
Lammert 4 , Jacob Nattermann 1,2 , Achim Hoerauf 3,2 , Christian
P. Strassburg 1,2 , Ulrich Spengler 1,2 , Hans Dieter Nischalke 1,2 ;
1 Department of Internal Medicine I, Bonn, Germany; 2 German
Center for Infection Research, Bonn, Germany; 3 Institute for Medical
Microbiology, Immunology and Parasitology, University of
Bonn, Bonn, Germany; 4 Department of Medicine II, Saarland University
Medical Center, Homburg, Germany
Aim: Spontaneous bacterial peritonitis (SBP) is frequently a
fatal infection in patients with advanced liver cirrhosis. We
investigated if NDP52 (nuclear dot protein 52 kDa), a negative
regulator of toll-like receptor signalling and an autophagy
adaptor protein, might be involved in the development of SBP.
Methods: Two cohorts comprising 152 (derivation cohort) and
198 patients (validation cohort) with liver cirrhosis and ascites
as well as 168 healthy controls were genotyped for the NDP52
Val248Ala variant and stratified for the occurrence of SBP.
Results: Overall, 57 (38%) patients in the derivation cohort
and 77 (39%) in the validation cohort had SBP. Cirrhosis was
due to alcohol abuse in 57% of the derivation and 66% of the
validation cohort. NDP52 genotype distribution was consistent
with Hardy-Weinberg equilibrium. In patients with alcoholic
cirrhosis, patients with SBP had an increased frequency of
the NDP52 minor variant in the derivation (p=0.04) and in
the validation cohort (p=0.01). In patients with liver cirrhosis
of non-alcoholic etiology, the frequency of the NPD52 minor
variant was comparable between patients with and without
SBP (11.3% versus 12.2%). Multivariate analysis confirmed
the NDP52 minor variant (odds ratio 4.7, p=0.002) and the
TLR2 -16934 TT variant (odds ratio 2.5, p=0.008) as independent
risk factors for SBP in alcoholic liver disease. Analysis
of the interaction between the TLR2 and the NDP52 risk
variant revealed that patients carrying both risk variants had
a particularly high risk to acquire SBP. Conclusion: Presence
of the NPD52 minor variant is a risk factor for SBP in patients
with alcoholic cirrhosis, indicating that autophagy might be
involved in the pathogenesis of SBP.
Disclosures:
Christian P. Strassburg - Advisory Committees or Review Panels: Novartis, Roche;
Speaking and Teaching: Novartis, Merz, MSD, Falk Pharma, BMS, Abbvie
The following authors have nothing to disclose: Philipp Lutz, Benjamin Krämer,
Dominik J. Kaczmarek, Marc P. Hübner, Bettina Langhans, Beate Appenrodt,
Frank Lammert, Jacob Nattermann, Achim Hoerauf, Ulrich Spengler, Hans Dieter
Nischalke
2078
Assessment and relevance of coagulation disorders in
patients with acute-on-chronic liver failure during Systemic
Inflammatory Response (SIRS) and development of
sepsis
Madhumita Premkumar, Priyanka Saxena, Roshni Mirza, Sukriti
Sukriti, Chhagan Bihari, Ashok Choudhary, Chandan K. Kedarisetty,
Shiv K. Sarin; Hepatology, Institute of Liver and Biliary Sciences,
Delhi, India
Background: Coagulation system is rebalanced in cirrhosis.The
status of baseline coagulation disturbances in ACLF and their
alterations with development of sepsis are largely unknown.
Aim: To study the dynamic changes in coagulation profile in
ACLF, and their correlation with evolving SIRS and sepsis.
Patients and Methods : Of the 243 consecutive patients with
ACLF (APASL criteria), 114 with no evidence of sepsis were
recruited (mean age 44.3±11.7 yr, males 90%). Predominant
etiology for underlying liver disease was ethanol (63.1%).
Patients were evaluated by tests like INR and thromboelastography
(TEG), Sonoclot, and coagulation factor assays.
These results were compared with 25 controls. At presentation
40/114 (35.1%) had SIRS. Twenty eight (24.5%) developed
sepsis by day 3 and 52/112 (56.1%) by day 7. Only 11 /74
(14.8%) developed sepsis de novo without prior SIRS. SIRS at
presentation posed a mortality risk of 48%. A deranged TEG
at presentation was a predictor of bleeding (OR 2.1, p=0.05)
and mortality (OR 3.1, p=0.05).Platelet count and functions (as
predicted by sonoclot) were significantly lower in ACLF patients
with sepsis at day 3 and 7. INR at baseline was associated
with a deranged R and K component of TEG (p=0.05) and
ACT of Sonoclot (p=0.02). Baseline ACT, CR and PF (sonoclot
parameters), were associated with development of SIRS at day
3 (p=0.013) and sepsis at day 7( p=0.012). Likewise R and
K of TEG (p=0.064) predicted sepsis. Coagulation assays for
protein C,and antithrombin III were lower in all ACLF patients,
when compared with controls, but did not change with sepsis.
Factor 8 levels were significantly increased in all ACLF
subgroups. Conclusions: Coagulation abnormalities in ACLF
are associated and correlate with an increased tendency to
bleed, risk of sepsis and mortality. Coagulation parameters
such as INR, TEG and Sonoclot are affected by presence of
SIRS. Sonoclot parameters at baseline can serve as predictors
of development of sepsis and poor outcome
Table 1: Coagulation parameters of ACLF when compared with
those with sepsis at day 3 and day 7.
ACT :Activated coagulation time
Disclosures:
The following authors have nothing to disclose: Madhumita Premkumar, Priyanka
Saxena, Roshni Mirza, Sukriti Sukriti, Chhagan Bihari, Ashok Choudhary, Chandan
K. Kedarisetty, Shiv K. Sarin
2079
Characteristics and outcome of Severe Alcoholic Hepatitis-related
Acute-on-Chronic Liver Failure Syndrome
Alexia Cornillie, Eric Trépo, Delphine Degré, Jonas Schreiber,
Antonia Lepida, Christophe Moreno, Thierry Gustot; Gastroenterology
and Hepato-Pancreatology, Erasme Hospital, Université
Libre de Bruxelles, Brussels, Belgium
Background & Aims: Although active alcoholism is known to
be a potential trigger for Acute-on-Chronic Liver Failure (ACLF),
place of severe alcoholic hepatitis (AH) as precipitating event is
currently unknown. We assessed characteristics, outcome and
predictive factors for the development of ACLF in patients with
severe biopsy-proven alcoholic hepatitis (AH). Methods: We
prospectively followed 145 consecutive biopsy-proven severe
AH (mDF≥32) episodes for 6 months. We retrospectively
reviewed ACLF diagnosis, grades (based on CANONIC criteria)
and prognostic scores, CLIF-C Organ Failure score (OFs)
and CLIF-C ACLFs (Jalan et al. J Hepatol 2014;61:1038-47) at
the time of liver biopsy (baseline) and at different time points