Project title
Metabolomic profile - a non-Invasive MarkEr of sponTaneous bacterial perItonitis in patients with decompensated Cirrhosis (Acronyme MIMETIC)
Source of funding
A grant of the Romanian National Authority for Scientific Research and Innovation, CNCS – UEFISCDI.
Project code
PN-II-RU-TE-2014-4-0709
Project director
Name: Bogdan Dumitru Procopeț, MD, PhD
Position: Assistant Lecturer, Department of Gastroenterology and Hepatology, Prof. Dr. Octavian Fodor Regional Institute of Gastroenterology and Hepatology, Iuliu Hațieganu University of Medicine and Pharmacy Cluj-Napoca
Email: bogdanprocopet@gmail.com
Research Team
-
Bogdan Dumitru Procopeț - project director
-
Horia Ștefănescu
-
Perta Fischer
-
Andreea Pop
-
Andreea Benea
Project description
Cirrhosis is the end stage disease of any chronic liver injury, regardless of the etiology. The natural history of cirrhosis is marked by the transition from a compensated stage, in which patients have low mortality rates, to a decompensated stage, with high liver-related mortality rates. Ascites is the most frequent decompensating event. Additionally, the occurrence of infections or renal impairment dramatically increases the mortality. Spontaneous bacterial peritonitis (SBP) is the most frequent infection in patients with cirrhosis and ascites, and represents the most common risk factor for acute renal impairment, manifested as hepatorenal syndrome. Therefore, the rapid identification of risk factors for SBP and rapid diagnosis of SBP is mandatory in order to offer rapid and appropriate treatment. New diagnostic markers of SBP are needed, especially if they are able to differentiate between etiological factors (Gram-negative or Gram-positive bacteria). Bacterial translocation occurs in up to 30% of patients with advanced liver disease and may be caused by either viable bacteria, as in the case of SBP, or bacterial fragments, such as bacterial DNA or endotoxin, inducing pro-inflammatory changes (an increase in proinflammatory cytokines (TNF-a, IL-12), nitric oxide metabolites) and increase plasma renin activity, that finally promote systemic circulatory abnormalities and intrahepatic endothelial dysfunction.The description of the metabolic profile of these patients’ serum and ascitic fluid will probably give an explanation for the individual differences in the risk of SBP occurrence and in the risk of infection related renal dysfunction, which influence deeply the prognosis of these patients.
Objectives
The major objectives:
1. To identify new markers and a specific metabolic profile for SBP in patients with decompensated
cirrhosis in serum and in the ascitic fluid.
2. To correlate these new metabolic markers with the markers of bacterial translocation (bacterial
DNA, bacterial lipopolysaccharide and lipopolysaccharide binding protein levels) and to investigate
whether the presence of bacteria or bacterial products in serum or ascites determinate a specific
metabolic profile.
3. To investigate if certain metabolites levels are associated with the type of the bacteria isolated in
the ascites fluid in patients with SBP.
Secondary objectives:
1. To compare the metabolic profile of patients with decompensated and compensated cirrhosis and with normal individuals in order to exclude overlapping in metabolomics and to characterize the different stages of the disease.
2. To investigate if the metabolic profile is different between patients with SBP and cirrhosis with other infections.
Expected results
1. The descripton, for the first time, of the metabolic profile of cirrhotic patients with SPB.
2. New diagnostic tests could be proposed based on the identified metabolites (the ones that are disease specific)
3. A rapid etiologic diagnostic test (Gram-negative or Gram-positive) using the metabolomic profile of the ascitic fluid, leading to better empirical treatments.
4. The comparisson of the metabolomics of SBP patients with cirrhotic patients with other infections and the identification of a cluster class of metabolites specific to infections in cirrhosis.
Plan of project realization
Milestones
1. January 1st, 2016: preliminary analysis of all healthy controls and at least 15 patients from the other groups.
2. Deliverables (article and presentations in international meetings):
2a. April 1st, 2016
2b. April 1st, 2017
Oral Prestentations
1. Metabolomics: in the search for new biomarkers of decompensation and infection in patients with cirrhosis - Petra Fischer, Corina Hebristean, Oana Farcau, Crina Grigoras, Anca Bugariu, Andreea Benea, Horia Stefanescu, Marcel Tantau, Carmen Socaciu, Bogdan Procopet - 25th UEGW Week, Barcelona 28.10-1.11.2017
(Awarded with Travel Grant)
2. The metabolic profile of decompensation in patients with cirrhosis - Bogdan Procopeț, 4th UpDate in Hepatology Course, Bucharest, 6-7.04.2017
3. Bacterial infections in end stage liver disease - Bogdan Procopeț, 24th UEGW Week, 15 - 19.10.2016, Vienna
Posters
1. For diagnosis of acute kidney injury in decompensated cirrhosis the estimation of baseline serum creatinine using Modification of Diet in Renal Disease formula is not accurate enough - Petra Fischer, Andreea Pop, Anca Bugariu, Horia Stefanescu, Daniela Matei, Marcel Tantau, Bogdan Procopet - The International Liver Congress EASL, Amsterdam, 19-23.04.2017
2. Decompensated cirrhosis is associated significantchanges in phosphatidylcholine metabolism - Petra Fischer, Corina Hebristean, Oana Farcau, Crina Grigoras, Anca Bugariu, Andreea Benea, Horia Stefanescu, Marcel Tantau, Carmen Socaciu, Bogdan Procopet - Al XXXVII-lea Congres Naţional de Gastroenterologie, Hepatologie şi Endoscopie Digestivă, 22-24 Iunie 2017, Bucureşti
