Steatosis is a condition of hepatic fat overload that is associated with overweight and the metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease with a global impact on healthcare. A proportion of NAFLD patients develops nonalcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis or hepatocellular carcinoma (HCC). Identifying patients at risk for potentially life-threatening complications is crucial in their prevention, surveillance and treatment. In addition to hepatic disease progression (cirrhosis, portal hypertension, HCC), NAFLD patients are also at risk of cardiovascular and metabolic diseases as well as extrahepatic malignancies. Liver fibrosis is related to morbidity and mortality in NASH patients, and biomarkers, imaging techniques (ultrasound, elastography, MRI) as well as liver biopsy help in diagnosing fibrosis. In this review, we discuss the tools for identifying patients at risk and their reasonable application in clinical routine in order to stratify prevention and treatment of this emerging disease.
This study investigates the effectiveness of a same-day polymerase chain reaction (PCR) test for the rapid detection of methicillin-resistant Staphylococcus aureus (MRSA) in a general screening of patients admitted to the trauma surgery and heart surgery department in a German university hospital. A total of 442 patients were screened over a 4-month period by using a PCR assay, compared to culture methods, for specimens from the nose and throat. The MRSA carriage rate on admission was 3.85% during the study period. The PCR results of 1,680 swabs showed a sensitivity of 85% and a specificity of 99.39% for swabs from the nares and for the throat 42.11% and 98.78%, respectively. A combination of specimens from the nose and throat from the same patient led to a sensitivity of 100% with a specificity of 98.29%. Cost calculation under the circumstances of a diagnosis-related groups (DRG) payment system found that the eight MRSA-positive patients created costs of 38,472 euros, i.e. 4,809 euros per patient, facing screening costs of 36.62 euros per sample. Screening patients by using the rapid PCR assay for a combination of specimens from the nose and throat would offer a safe and cost-effective way of MRSA screening on admission.
Bile acids (BA) as important signaling molecules are considered crucial in development of cholestatic liver injury, but there is limited understanding on the involved cell types and signaling pathways. The aim of this study was to evaluate the inflammatory and fibrotic potential of key BA and the role of distinct liver cell subsets focusing on the NLRP3 inflammasome. C57BL/6 wild-type (WT) and Nlrp3−/− mice were fed with a diet supplemented with cholic (CA), deoxycholic (DCA) or lithocholic acid (LCA) for 7 days. Additionally, primary hepatocytes, Kupffer cells (KC) and hepatic stellate cells (HSC) from WT and Nlrp3−/− mice were stimulated with aforementioned BA ex vivo. LCA feeding led to strong liver damage and activation of NLRP3 inflammasome. Ex vivo KC were the most affected cells by LCA, resulting in a pro-inflammatory phenotype. Liver damage and primary KC activation was both ameliorated in Nlrp3-deficient mice or cells. DCA feeding induced fibrotic alterations. Primary HSC upregulated the NLRP3 inflammasome and early fibrotic markers when stimulated with DCA, but not LCA. Pro-fibrogenic signals in liver and primary HSC were attenuated in Nlrp3−/− mice or cells. The data shows that distinct BA induce NLRP3 inflammasome activation in HSC or KC, promoting fibrosis or inflammation.
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