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Abstract: Introduction: Fibrogenesis is a typical reaction of the liver to injury. In the case of overstimulation of fibrogenesis clinically significant fibrosis and, eventually, cirrhosis occur. Treatment of liver cirrhosis is limited, therefore it is important to screen and monitor patients at risk of cirrhosis. Noninvasive parameters are ideal for this purpose due to their risk profile and repeatability. Methods: Systematic review of literature. Results: Among large number of proposed biomarkers, there is a distinct difference between two groups or classes. Class I biomarkers are associated with the process of fibrogenesis, their presence in the serum is the result of the increased turnover of extracellular matrix. Class II biomarkers and their combinations are mostly markers of liver function or structural damage. We have identified 27 Class I and 13 Class II biomarkers that have been proposed in the literature. We have evaluated in detail those which reached limited clinical application. Conclusion: General clinical acceptance of these biomarkers is low because of various drawbacks. Simple and readily available biomarkers have low accuracy in predicting liver fibrosis and more advanced markers have low cost–benefit ratio. Therefore liver biopsy remains the “gold standard” for diagnosis of fibrosis. However potential noninvasive alternatives exist and their implementation could be valuable. [Copyright &y& Elsevier]

Abstract: Background: Fibrosis is the excessive deposition and histological redistribution of extracellular matrix (ECM) in the tissue as consequence of chronic liver damage. It leads to progressive liver insufficiency, portal hypertension and ultimately to cirrhosis and primary liver cell carcinoma. There is a strong demand for reliable, organ- and disease-specific, non-invasive biomarkers of fibrosis and fibrogenesis to replace or to complement the invasive method of needle biopsy, which is afflicted with a high degree of sampling error. Methods: A systematic literature search was performed using electronic databases and reference lists of relevant publications to ascertain studies with non-invasive biomarkers of liver fibrosis. Results: Two classes of serum biomarkers can be differentiated: Class I markers are those, which reflect ECM turnover (fibrogenesis and fibrolysis) and/or fibrogenic cell changes, mainly of hepatic stellate cells, which are the dominant profibrogenic cell type in liver. They are mostly cost intensive, single laboratory tests and derive from the translation of fibrogenic mechanisms into clinical application. Examples are procollagen peptides, hyaluronan, and laminin. Class II biomarkers are based on algorithmic evaluation of commonly observed functional alterations of the liver that do not necessarily reflect ECM metabolism and/or fibrogenic cell changes. About 20 numerical scores or indices are reported for parameters, which are mostly routine laboratory tests and frequently multiparametric (panels). Among them fibrotest, hepascore, ELF-score have reached limited clinical application. Conclusions: Up to now the impact of both classes of biomarkers for diagnosis and monitoring of fibrosis, fibrogenesis, and fibrolysis is limited. They cannot replace needle biopsy but some of them might be complementary in follow-up studies. Innovative methods like proteomics and glycomics to establish fibrosis-specific serum protein and glycosylation patterns, respectively, might have a high potential for diagnosis and monitoring of fibrogenesis. [Copyright &y& Elsevier]

Almost 99% of the body magnesium is inside cells. The concentration of intracellular ionized magnesium (iMg) is physiologically relevant. iMg in erythrocytes is a new parameter that can help to establish reliable information on the functional magnesium status.iMg concentration in erythrocytes and serum was measured by ion-selective electrode, in clinical analyzer Microlyte (KONE). Total magnesium (tMg) concentration was measured by atomic absorption spectrometry (AAS). Albumin and total protein concentration were measured colorimetrically.In critically ill postoperative patients, the mean of albumin, protein and hematocrit concentration was significantly lower compared to healthy individuals. Hypomagnesemia was found in 15.9% patients as tMgs, at 22.2% as iMgs and 36.5% as iMge. Significant correlations are between iMgs and tMgs or iMge and iMgs/tMgs. In dialyzed patients, the mean of hematocrit was significantly lower, iMge was significantly higher compared with healthy individuals. Significant negative correlations are between iMgs and tMge or iMge/tMge and tMge.iMge is the best magnesium parameter to observe hypo- or hypermagnesemia for both groups of patients. The function of magnesium is mainly intracellular and intracellular magnesium concentrations can be the method to evaluate the magnesium status. [Copyright &y& Elsevier]

Background: Typically, endometriosis is diagnosed surgically by laparoscopy. CA-125 is the principal serum marker used in the diagnosis and management of late-stage endometriosis. The search for a body fluid marker of early stage disease has included studies of serum, peritoneal fluid (PF), and/or tissue levels of secretory proteins, cell adhesion molecules, cytokines, tumor necrosis and vascular endothelial growth factors (VEGFs), chemokines, antiendometrial antibodies, autoantibodies to oxidized lipoproteins, aromatase P-450 expression, cytokeratins, and hormone receptors. We compared the diagnostic accuracy and clinical utility of these various types of substances in the non-surgical identification of patients with endometriosis. Method: We reviewed the MEDLINE database for all publications on serum, peritoneal fluid and tissue markers of endometriosis. Results: Except for serum interleukin (IL)-6 and peritoneal fluid tumor necrosis factor (TNF)-α levels, the diagnostic accuracy of other markers of endometriosis was either similar or worse than that of CA-125 (sensitivity 24–94%; specificity 83–93%). The diagnostic accuracy of IL-6 and TNF-α was 90–100% (sensitivity) and 67–89% (specificity). Conclusion: CA-125 has limited diagnostic accuracy in the identification of early stage endometriosis and none of the other markers we reviewed dramatically outperformed CA-125 in this regard with the possible exception of serum IL-6 and peritoneal fluid TNF-α levels. [Copyright &y& Elsevier]