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Liver dysfunction (LD) and liver failure are associated with poor outcome in critically ill patients. In patients with severe sepsis or septic shock, LD occurred in nearly 19% of patients. An early diagnosis of LD at time of initial damage of the liver can lead to a better prognosis of these patients because an early start of therapy is possible. We performed a second prospective study with septic patients to test a new cell-based cytotoxicity device (biosensor) to evaluate clinical relevance for early diagnosis of LD and prognostic capacity. In the clinical study, 99 intensive care unit patients were included in two groups. From the patients of the septic group (n = 51, SG), and the control (non-septic) group [n = 49, control group (CG)] were drawn 20 ml blood at inclusion, after 3, and 7 days for testing with the biosensor. Patients’ data were recorded for hospital survival, organ function, and demographic data, illness severity [acute physiology and chronic health evaluation (APACHE) II-, sepsis-related organ failure assessment (SOFA) scores], cytokines, circulating-free deoxyribonucleic acid/neutrophil-derived extracellular traps (cf-DNA/NETs), microbiological results, and pre-morbidity. For the developed cytotoxicity test, the human liver cell line HepG2/C3A was used. Patients’ plasma was incubated in a microtiter plate assay with the test cells and after 6 days incubation the viability (trypan blue staining, XTT-test) and functionality (synthesis of albumin, cytochrome 1A2 activity) was analyzed. An impairment of viability and functionality of test cells was only seen in the SG compared with the CG. The plasma of non-survivors in the SG led to a more pronounced impairment of test cells than the plasma of survivors at inclusion. In addition, the levels of cf-DNA/NETs were significantly higher in the SG at inclusion, after 3, and after 7 days compared with the CG. The SG showed an in-hospital mortality of 24% and the values of bilirubin, APACHE II-, and SOFA scores were markedly higher at inclusion than in the CG. Hepatotoxicity of septic plasma was already detected with the liver cell-based biosensor at inclusion and also in the course of disease. The biosensor may be a tool for early diagnosis of LD in septic patients and may have prognostic relevance. [ABSTRACT FROM AUTHOR]

Severe hepatosplenic injury of mansonian schistosomiasis is caused by Th2 mediated granulomatous response against parasite eggs entrapped within the periportal tissue. Subsequent fibrotic scarring and deformation/sclerosing of intrahepatic portal veins lead to portal hypertension, ascites, and oesophageal varices. The murine model of Schistosoma mansoni (S. mansoni) infection is suitable to establish the severe hepatosplenic injury of disease within a reasonable time scale for the development of novel antifibrotic or anti-infective strategies against S. mansoni infection. The drawback of the murine model is that the material prepared for complex analysis of egg burden, granuloma size, hepatic inflammation, and fibrosis is limited due to small amounts of liver tissue and blood samples. The objective of our study was the implementation of a macroscopic scoring system for mice livers to determine infection-related organ alterations of S. mansoni infection. In addition, an in vitro biosensor system based on the detection of hepatocellular injury in HepG2/C3A cells following incubation with serum of moderately (50 S. mansoni cercariae) and heavily (100 S. mansoni cercariae) infected mice affirmed the value of our scoring system. Therefore, our score represents a valuable tool in experimental schistosomiasis to assess severity of hepatosplenic schistosomiasis and reduce animal numbers by saving precious tissue samples. [ABSTRACT FROM AUTHOR]