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Results of a second prospective study: Liver-cells based biosensor in patients with septic shock

: Sauer, M.; Haubner, C.; Brenner, J.; Potschka, H.; Mencke, T.; Mitzner, S.; Nöldge-Schomburg, G.

Intensive Care Medicine 40 (2014), Supplement, pp.S31
ISSN: 0342-4642
ISSN: 0342-4642
European Society of Intensive Care Medicine (ESICM Annual Congress) <27, 2014, Barcelona>
Fraunhofer IZI ()

INTRODUCTION. Nearly 19 % of patients with severe sepsis developed liver dysfunction or failure in the course of disease (1). The late diagnosis of liver failure is a major problem in critically ill patients. Early diagnosis of liver dysfunction and failure can enable early onset of therapy and may lead to an improvement of prognosis of these patients.
OBJECTIVES. To verify the clinical relevance of a new test device for early diagnosis of liver failure, we conducted a second study with severe septic patients. A first study revealed, that plasma from septic patients lead to an impairment of viability and function of sensorcells (2).
METHODS. We developed a new test device for early diagnosis of liver failure (patent pending). The basic test compounds consist of human liver cells (HepG2/C3A). In a standardised mikrotiterplate assay the toxicity of patient plasma was tested (500.000 cells/ well). After incubation with plasma from patients the viability of cells (XTT test, Trypan blue-staining), the cytochrome 1A2 activity (metabolism of etoxyresorufin) and synthesis of albumin are measured. In a prospective clinical study in 99 ICU-patients two test groups were studied: the septic shock group (n = 51, SSG) and the non-septic shock group (n = 49, NSG) as control group. At time of inclusion, after 3 and 7 days, 10 ml blood was drawn from the patients for testing with the cytotoxicity test. Patients were followed up for hospital survival. The results are expressed as median and range. Differences were considered significant at p\0.05. Significance was determined with the Mann–Whitney U-test.
RESULTS. The in-hospital mortality was 23.5 % in the SSG; one patient of the NSG died. The APACHE II-scores at ICU arrival were 32 (15) in the SSG and 9 (10) in the NSG, the SOFA-scores at inclusion were 13 (6.8) in the SSG and 2 (4.6) in the NSG. The values of bilirubin (SSG-Survivors: 19.2 lmol/l (26.6), SSG-Non-Survivors: 21.4 (88.2), NSG: 15.2 (17)) were significantly higher and the Prothrombin-time lower in the SSG (Survivors: 73 % (32.8), Non-Survivors: 66 (22.8)) than in the NSG 90 (25.8). The plasma of patients with septic shock impaired significantly viability and cellular functions of HepG2/C3A cells in all parameters compared with the plasma of non-septic patients. These effects were more pronounced with plasma of non-survivors in the SSG at inclusion, after 3 and 7 days (data not shown).
CONCLUSIONS. The presented liver cells based biosensor showed hepatotoxicity of plasma from patients with septic shock in a second study; moreover, these effects were more pronounced in non-survivors. The new test may contribute to an early diagnosis of liver failure in septic patients.