studies

1216A AASLD ABSTRACTS HEPATOLOGY, October, 2015
as proportions of resistances mutations maintain a relatively
low level. Genotypic resistance to ETV was detected in all the
partial responders with long-term therapy. The threshold related
to substisutions requires corroboration by further studies with
large samples to determine whether adapt the therapy.In addition
to the common substitutions, the unknown amino acid substitutions,
such as rtL145M/S, rtF151Y/L,rtR153Q, rtI224V,
rtN248H, rtS223A, rtS256C,are also likely to influence the
outcome of treatment.
Disclosures:
The following authors have nothing to disclose: Xiaxia Zhang, Minran Li, Ying
Cao, Yu Zhang, Renwen Zhang, Yang Xu, Fang Li, Xiaoyuan Xu
2067
A Broad Spectrum Antibiotic Therapy As Empirical
Treatment In Healthcare-Associated Infections Improves
Survival In Cirrhotic Patients: A Randomized Trial
Cristina Lucidi, Vincenza Di Gregorio, Barbara Lattanzi, Valerio
Giannelli, Michela Giusto, Oliviero Riggio, Mario Venditti, Manuela
Merli; Sapienza University of Rome, Rome, Italy
Background and aims: An early diagnosis and an appropriate
treatment of infections in cirrhosis are crucial due to their high
morbidity and mortality. Multidrug-resistant (MDR) infections
are growing in healthcare setting. Frequently, Healthcare-associated
(HCA) infections are treated as community-acquired
with a detrimental effect on survival. We aimed to prospectively
evaluate for the first time in a randomized trial the effectiveness
of a broad spectrum antibiotic treatment cirrhotic
patients with HCA infections. Methods: Consecutive cirrhotic
patients with HCA infections hospitalized in the last 3 years
in our ward were enrolled. After culture sampling, patients
were promptly randomized to empirically receive a standard
or a broad spectrum antibiotic treatment (NCT01820026). The
primary endpoint was the in-hospital mortality with the aim of
66% reduction. Efficacy, sides effects, development of second
infections and length of hospitalization was also considered.
Treatment failure was followed by modification of therapies
as appropriate. Results: As originally designed, 96 patients
were randomized but 94 completed the treatment and were
analyzed (two were excluded for incorrect randomization due
to neoplastic ascites). Patients belonging to standard (48) and
broad spectrum (46) groups were similar for demographic,
clinical, and microbiological characteristics. The prevalence of
MDR pathogens was similar in the 60 microbiologically documented
infections (40% in standard vs 46% in broad spectrum
group, p=ns). In-hospital mortality showed a 76% reduction
in the broad spectrum vs standard group (respectively, 6% vs
25%; p=0.01); the shift to another antibiotic treatment was not
possible in about 20% of death patients. The standard therapy
failed more often than the broad spectrum one (51 vs 18%,
p=0.001). The length of the hospitalization was longer in the
Standard Group (18 ± 15 days) than in the Broad Spectrum
Group (12.3 ± 7 days) (p= 0.03). Only one patient showed
a not severe side effect related to antibiotic treatment. Ten
patients (12% of the group 1 and 9% of the group 2) developed
a second episode of infection during the hospitalization
with a similar prevalence of MDR of (60% in standard vs
50% in broad spectrum, p=ns). Conclusions: A broad spectrum
antibiotic therapy as empirical treatment in HCA infections
improves survival in cirrhotic patients. This treatment resulted
significantly effective, safe and cost-saving.
Disclosures:
The following authors have nothing to disclose: Cristina Lucidi, Vincenza Di
Gregorio, Barbara Lattanzi, Valerio Giannelli, Michela Giusto, Oliviero Riggio,
Mario Venditti, Manuela Merli
2068
Probiotic supplementation improves liver function but
fails to restore neutrophil phagocytosis in stable cirrhosis.
A randomized, double-blind, placebo-controlled
study
Angela Horvath, Bettina Leber, Bianca Schmerboeck, Monika
Tawdrous, Astrid Hartl, Sandra Lemesch, Peter Fickert, Rudolf E.
Stauber, Philipp Stiegler, Franziska Durchschein, Elisabeth Krones,
Philipp Douschan, Gernot Zollner, Walter Spindelboeck, Karl
Oettl, Doris Payerl, Vanessa Stadlbauer; Medical University Graz,
Graz, Austria
A multispecies probiotic was administered to cirrhotic patients
in order to strengthen gut barrier function, decrease endotoxin
load and ultimately restore phagocytic dysfunction of neutrophils
that is commonly found in cirrhosis. Therefore, stable
cirrhotic patients received either a mixture of Bifidobacteria bifidum
and lactis, Lactobacili acidophilus, brevis, casei and salivarius,
and Lactococcus lactis sp. (n=44) or a placebo (n=36)
for 6 months. We found that during the intervention period
the percentage of patients with Child-Pugh grade A increased
significantly from 63% to 70% after three months and 66%
after six months, only in the probiotic group. Of 16 patients
in the probiotic group that started the study with Child-Pugh
score 7 or higher, 6 improved their score after 6 months of
probiotics, 7 did not change but only 3 deteriorated. Median
Child-Pugh score decreased from 6 to 5 after three months of
probiotics and MELD score decreased non-significantly from
12 to 11 during the intervention period but returned to baseline
6 months after intervention had ended. Gut permeability,
measured with Lactulose-Mannitol ratio, improved significantly
in both groups. With probiotics it remained significantly lower
than baseline 6 months after the intervention has ended. On
the other hand sucrose recovery, calprotectin and zonulin in
stool and serum diamine oxidase stayed unchanged in both
groups. Endotoxin levels decreased non-significantly with probiotics
but similar changes occurred in the control group. Cytokine
levels as well as soluble CD14 and LPS binding protein
stayed unchanged in both groups. Probiotic supplementation
did not have a significant influence on neutrophil phagocytosis.
At baseline both groups had an intact phagocytic capacity but
a significantly increased amount of non-phagocytic neutrophils
compared to controls. Over the course of the study the amount
of non-phagocytic cells remained constant while phagocytic
capacity decreased to 60% of the baseline value. During the
first 6 months of the study 1 severe infection occurred in the
placebo group, none in the probiotic group. After intervention
had ended 5 severe infections were reported in the probiotic
group and 4 in the placebo group. In conclusion, probiotic
supplementation is a save method to improve liver function in
stable cirrhosis. However, its influence on gut barrier function
and bacterial translocation in cirrhotic patients seem to be minimal.
Independent of the intervention, patients gradually developed
significant impairment in neutrophil phagocytosis over
the course of one year and with this loss of function a higher
incidence of severe infections occurred.
Disclosures:
Angela Horvath - Grant/Research Support: Instutut Allergosan
Peter Fickert - Consulting: Falk Foundation, Falk Foundation, Falk Foundation,
Falk Foundation; Speaking and Teaching: Roche Austria, Gilead Austria, MSD
Austria, MERCK Austria, Roche Austria, Gilead Austria, MSD Austria, MERCK
Austria, Roche Austria, Gilead Austria, MSD Austria, MERCK Austria, Roche
Austria, Gilead Austria, MSD Austria, MERCK Austria
Rudolf E. Stauber - Advisory Committees or Review Panels: Gilead, Janssen-Cilag,
AbbVie, BMS; Grant/Research Support: MSD; Speaking and Teaching: Merz
The following authors have nothing to disclose: Bettina Leber, Bianca Schmerboeck,
Monika Tawdrous, Astrid Hartl, Sandra Lemesch, Philipp Stiegler, Franziska
Durchschein, Elisabeth Krones, Philipp Douschan, Gernot Zollner, Walter
Spindelboeck, Karl Oettl, Doris Payerl, Vanessa Stadlbauer