Performance of Serum microRNAs -122, -192 and -21 as Biomarkers in Patients with Non-Alcoholic Steatohepatitis.
Philip P. Becker,Monika Rau,Johannes Schmitt,Carolin Malsch,Christian Hammer,Heike Bantel,Beat Müllhaupt,Andreas Geier +7 more
TLDR
Candidates for a combined model of miRNAs and CK18-Asp396 levels relevant as a promising expansion for diagnosis and in turn treatment of NASH are defined.Abstract:
Objectives Liver biopsies are the current gold standard in non-alcoholic steatohepatitis (NASH) diagnosis. Their invasive nature, however, still carries an increased risk for patients' health. The development of non-invasive diagnostic tools to differentiate between bland steatosis (NAFL) and NASH remains crucial. The aim of this study is the evaluation of investigated circulating microRNAs in combination with new targets in order to optimize the discrimination of NASH patients by non-invasive serum biomarkers. Methods Serum profiles of four microRNAs were evaluated in two cohorts consisting of 137 NAFLD patients and 61 healthy controls. In a binary logistic regression model microRNAs of relevance were detected. Correlation of microRNA appearance with known biomarkers like ALT and CK18-Asp396 was evaluated. A simplified scoring model was developed, combining the levels of microRNA in circulation and CK18-Asp396 fragments. Receiver operating characteristics were used to evaluate the potential of discriminating NASH. Results The new finding of our study is the different profile of circulating miR-21 in NASH patients (p<0.0001). Also, it validates recently published results of miR-122 and miR-192 to be differentially regulated in NAFL and NASH. Combined microRNA expression profiles with CK18-Asp396 fragment level scoring model had a higher potential of NASH prediction compared to other risk biomarkers (AUROC = 0.83, 95% CI = 0.754-0.908; p<0.001). Evaluation of score model for NAFL (Score = 0) and NASH (Score = 4) had shown high rates of sensitivity (91%) and specificity (83%). Conclusions Our study defines candidates for a combined model of miRNAs and CK18-Asp396 levels relevant as a promising expansion for diagnosis and in turn treatment of NASH.read more
Citations
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Noninvasive Assessment of Liver Disease in Patients With Nonalcoholic Fatty Liver Disease.
TL;DR: The current state of the noninvasive assessment of liver disease in NAFLD is summarized, and an expert synthesis of how these nonin invasive tools could be utilized in clinical practice is provided.
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Genetics and epigenetics of NAFLD and NASH: Clinical impact
TL;DR: The status of research into important genetic and epigenetic modifiers of NAFLD progression are discussed and the potential to translate the accumulating wealth of genetic data into the design of novel therapeutics and the clinical implementation of diagnostic/prognostic biomarkers will be explored.
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Noninvasive biomarkers in NAFLD and NASH - current progress and future promise.
Vincent Wai-Sun Wong,Leon A. Adams,Victor de Lédinghen,Grace Lai-Hung Wong,Silvia Cristina Sookoian,Silvia Cristina Sookoian +5 more
TL;DR: Current and potential biomarkers for different features of NAFLD, namely, steatosis, necroinflammation and fibrosis are reviewed, and MRI-estimated proton density fat fraction is currently the most accurate test to quantify hepatic steatohepatitis and can be considered the gold standard.
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Exosomes derived from palmitic acid-treated hepatocytes induce fibrotic activation of hepatic stellate cells
Young-Sun Lee,So Yeon Kim,Eunjung Ko,Jun Hee Lee,Hyon-Seung Yi,Yang Jae Yoo,Jihye Je,Sang Jun Suh,Young Kul Jung,Ji Hoon Kim,Yeon Seok Seo,Hyung Joon Yim,Won-Il Jeong,Jong Eun Yeon,Soon Ho Um,Kwan Soo Byun +15 more
TL;DR: PA treatment enhanced the production of exosomes in these hepatocytes and changed their exosomal miRNA profile, and exosome derived from PA-treated hepatocytes caused an increase in the expression levels of fibrotic genes in HSCs.
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Noninvasive evaluation of nonalcoholic fatty liver disease: Current evidence and practice.
TL;DR: Current noninvasive methods for assessing nonalcoholic fatty liver disease, including steatosis, NASH, and NAFLD-related fibrosis, are discussed and effective algorithms consisting of imaging and nonimaging biomarkers for diagnosing advanced fibrosis and reducing unnecessary biopsies in clinical practice are explored.
References
More filters
Journal ArticleDOI
The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association
Naga Chalasani,Zobair M. Younossi,Joel E. Lavine,Anna Mae Diehl,Elizabeth M. Brunt,Kenneth Cusi,Michael Charlton,Arun J. Sanyal +7 more
TL;DR: This is a practice guideline for clinicians rather than a review article and interested readers can refer to several comprehensive reviews published recently.
Journal ArticleDOI
Long-term follow-up of patients with NAFLD and elevated liver enzymes.
Mattias Ekstedt,Lennart Franzén,Ulrik Mathiesen,Lars Thorelius,Marika Holmqvist,Göran Bodemar,Stergios Kechagias +6 more
TL;DR: It is concluded that nonalcoholic fatty liver disease with elevated liver enzymes is associated with a clinically significant risk of developing end‐stage liver disease and Survival is lower in patients with NASH, and most NAFLD patients will develop diabetes or impaired glucose tolerance in the long term.
Journal ArticleDOI
Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis
TL;DR: Older age, obesity, and presence of diabetes mellitus help identify those NASH patients who might have severe liver fibrosis, and this is the subgroup of patients who would be expected to derive the most benefit from having a liver biopsy and considering investigational therapies.
Journal ArticleDOI
Circulating microRNAs, potential biomarkers for drug-induced liver injury
Kai Wang,Shile Zhang,Bruz Marzolf,Pamela Troisch,Amy Brightman,Zhiyuan Hu,Leroy Hood,David J. Galas +7 more
TL;DR: It is demonstrated that specific microRNA species, such as mir-122 and mir-192, both are enriched in the liver tissue and exhibit dose- and exposure duration-dependent changes in the plasma that parallel serum aminotransferase levels and the histopathology of liver degeneration, but their changes can be detected significantly earlier.
Journal ArticleDOI
A novel and universal method for microRNA RT-qPCR data normalization
Pieter Mestdagh,Pieter Van Vlierberghe,An-Sofie De Weer,Daniel Muth,Frank Westermann,Frank Speleman,Jo Vandesompele +6 more
TL;DR: It is demonstrated that the mean expression value outperforms the current normalization strategy in terms of better reduction of technical variation and more accurate appreciation of biological changes.