المؤلفون: Raluca Pais, Rachel Ostroff, Stephen Harrison, Lars Friis Mikkelsen, Elisabeth Erhardtsen, Sudha Shankar, Kimmo Porthan, Jérôme Boursier, Antonia Sinisi, Michael Kalutkiewicz, Sven Francque, Miljen Martic, Vanessa Pellegrinelli, Phil N. Newsome, Guido Hanauer, Hannele Yki-Järvinen, Rebecca Darlay, Joel Myers, Carla Yunis, Salvatore Petta, Mette Skalshøi Kjær, Pablo Ortiz, Ann K. Daly, James H. Clark, Dina Tiniakos, Yasaman Vali, Hadi Zafarmand, Matej Orešič, Maurizio Parola, Estelle Sandt, Lori L. Jennings, Matt Kelly, Tuulia Hyötyläinen, Detlef Schuppan, Céline Fournier, Chiara Rosso, Diane E. Shevell, Maria Manuela Tonini, Paul Hockings, Aidan McGlinchey, Salma Akhtar, Mette Juul Fisker, Morten A. Karsdal, Diane Whalley, Melissa R. Miller, Aldo Trylesinski, Mattias Ekstedt, Stefan Neubauer, Jeremy M. Palmer, Partho Sen, Michael Pavlides, Per Qvist, Isabel Fernández, Luca Miele, Fabio Marra, Stergios Kechagias, Richard Torstenson, Katherine Johnson, Jean-François Dufour, Elisabetta Bugianesi, M. Julia Brosnan, George V. Papatheodoridis, Kay M. Pepin, Daniel Guldager Kring Rasmussen, Henrik Landgren, Rachel Queen, Simon Cockell, Michael Allison, Patrick M.M. Bossuyt, Rocío Gallego-Durán, Christian Rosenquist, Leigh Alexander, Elizabeth Shumbayawonda, Michele Vacca, Antonio Vidal-Puig, David Wenn, Rémy Hanf, Oscar Millet, Michalina Zatorska, R. Myers, José M. Mato, Jenny Lee, Theresa Tuthill, James Twiss, Ramy Younes, Peter Leary, Lynda Doward, Kristy Wonders, Guruprasad P. Aithal, Sarah Charlton, Vlad Ratziu, Cecília M. P. Rodrigues, Christian Trautwein, Helena Cortez-Pinto, Gideon Ho, Matt J. Barter, Judith Ertle, Jörn M. Schattenberg, Maria-Magdalena Balp, Yang-Lin Liu, Clifford A. Brass, Olivier Govaere, Amalia Gastaldelli, Sergio Rodriguez Cuenca, Pierre Chaumat, Fiona Oakley, Luca Valenti, Simon J. Cockell, Saskia W.C. van Mil, Ferenc E. Mózes, Andreas Geier, Timothy Hardy, Pierre Bedossa, Andrea Dennis, Richard L. Ehman, Charlotte Erpicum, Karine Clément, Jeremy F. L. Cobbold, Christopher P. Day, Rajarshi Banerjee, Manuel Romero-Gómez, Quentin M. Anstee, Adriaan G. Holleboom, Heather J. Cordell, Kevin L. Duffin, Diana Julie Leeming

المساهمون: Epidemiology and Data Science, APH - Methodology, APH - Personalized Medicine, Vascular Medicine, ACS - Diabetes & metabolism, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, APH - Aging & Later Life, ARD - Amsterdam Reproduction and Development, Graduate School, Investigators, LITMUS Consortium, Johnson K., Leary P.J., Govaere O., Barter M.J., Charlton S.H., Cockell S.J., Tiniakos D., Zatorska M., Bedossa P., Brosnan M.J., Cobbold J.F., Ekstedt M., Aithal G.P., Clement K., Schattenberg J.M., Boursier J., Ratziu V., Bugianesi E., Anstee Q.M., Daly A.K., Clark J., Cordell H.J., Darlay R., Day C.P., Hardy T., Liu Y.-L., Oakley F., Palmer J., Queen R., Wonders K., Bossuyt P.M., Holleboom A.G., Zafarmand H., Vali Y., Lee J., Pais R., Schuppan D., Allison M., Cuenca S.R., Pellegrinelli V., Vacca M., Vidal-Puig A., Hyotylainen T., McGlinchey A., Oresic M., Sen P., Mato J., Millet O., Dufour J.-F., Harrison S., Neubauer S., Pavlides M., Mozes F., Akhtar S., Banerjee R., Kelly M., Shumbayawonda E., Dennis A., Erpicum C., Romero-Gomez M., Gallego-Duran R., Fernandez I., Karsdal M., Leeming D., Fisker M.J., Erhardtsen E., Rasmussen D., Qvist P., Sinisi A., Sandt E., Tonini M.M., Parola M., Rosso C., Marra F., Gastaldelli A., Francque S., Kechagias S., Yki-Jarvinen H., Porthan K., van Mil S., Papatheodoridis G., Cortez-Pinto H., Valenti L., Petta S., Miele L., Geier A., Trautwein C., Hockings P., Newsome P., Wenn D., Pereira Rodrigues C.M., Hanf R., Chaumat P., Rosenquist C., Trylesinski A., Ortiz P., Duffin K., Yunis C., Miller M., Tuthill T., Ertle J., Younes R., Alexander L., Ostroff R., Kjaer M.S., Mikkelsen L.F., Brass C., Jennings L., Balp M.-M., Martic M., Hanauer G., Shankar S., Torstenson R., Fournier C., Ehman R., Kalutkiewicz M., Pepin K., Myers J., Shevell D., Ho G., Landgren H., Myers R., Doward L., Whalley D., Twiss J., Miller, Melissa, Tuthill, Theresa, Ertle, Judith, Younes, Ramy, Alexander, Leigh, Ostroff, Rachel, Kjær, Mette Skalshøi, Mikkelsen, Lars Friis, Brass, Clifford, Jennings, Lori, Balp, Maria-Magdalena, Martic, Miljen, Hanauer, Guido, Shankar, Sudha, Torstenson, Richard, Fournier, Céline, Ehman, Richard, Kalutkiewicz, Michael, Pepin, Kay, Myers, Joel, Shevell, Diane, Ho, Gideon, Landgren, Henrik, Myers, Rob, Doward, Lynda, Whalley, Diane, Twiss, James, Clark, James, Cordell, Heather J., Darlay, Rebecca, Day, Christopher P., Hardy, Tim, Liu, Yang-Lin, Oakley, Fiona, Palmer, Jeremy, Queen, Rachel, Wonders, Kristy, Bossuyt, Patrick M., Holleboom, Adriaan G., Zafarmand, Hadi, Vali, Yasaman, Lee, Jenny, Clement, Karine, Pais, Raluca, Schuppan, Detlef, Allison, Michael, Cuenca, Sergio Rodriguez, Pellegrinelli, Vanessa, Vacca, Michele, Vidal-Puig, Antonio, Hyötyläinen, Tuulia, McGlinchey, Aidan, Orešič, Matej, Sen, Partho, Mato, Jose, Millet, Óscar, Dufour, Jean-Francois, Harrison, Stephen, Neubauer, Stefan, Pavlides, Michael, Mozes, Ferenc, Akhtar, Salma, Banerjee, Rajarshi, Kelly, Matt, Shumbayawonda, Elizabeth, Dennis, Andrea, Erpicum, Charlotte, Romero-Gomez, Manuel, Gallego-Durán, Rocío, Fernández, Isabel, Karsdal, Morten, Leeming, Diana, Fisker, Mette Juul, Erhardtsen, Elisabeth, Rasmussen, Daniel, Qvist, Per, Sinisi, Antonia, Sandt, Estelle, Tonini, Maria Manuela, Parola, Maurizio, Rosso, Chiara, Marra, Fabio, Gastaldelli, Amalia, Francque, Sven, Kechagias, Stergios, Yki-Järvinen, Hannele, Porthan, Kimmo, van Mil, Saskia, Papatheodoridis, George, Cortez-Pinto, Helena, Valenti, Luca, Petta, Salvatore, Miele, Luca, Geier, Andreas, Trautwein, Christian, Hockings, Paul, Newsome, Phil, Wenn, David, Pereira Rodrigues, Cecília Maria, Hanf, Rémy, Chaumat, Pierre, Rosenquist, Christian, Trylesinski, Aldo, Ortiz, Pablo, Duffin, Kevin, Yunis, Carla

المصدر: JHEP Reports, 4(2):100409. Elsevier
JHEP Reports
JHEP Reports, Vol 4, Iss 2, Pp 100409-(2022)
JHEP reports 4(2), 100409 (2022). doi:10.1016/j.jhepr.2021.100409

مصطلحات موضوعية: SCORING SYSTEM, CPM, counts per million, AUROC, area under the receiver operating characteristic, RC799-869, AST, aspartate aminotransferase, MicroRNA, Non-alcoholic fatty liver disease, Biomarker, Sequencing, TGF-β, transforming growth factor-beta, Gastroenterology, STEATOHEPATITIS, Liver disease, 0302 clinical medicine, Fibrosis, miRNA, microRNA, logFC, log2 fold change, FIBROSIS, Immunology and Allergy, 0303 health sciences, education.field_of_study, NAS, NAFLD activity score, medicine.diagnostic_test, Fatty liver, GTEx, Genotype-Tissue Expression, Diseases of the digestive system. Gastroenterology, 3. Good health, Real-time polymerase chain reaction, Biomarker, MicroRNA, Non-alcoholic fatty liver disease, Sequencing, Liver biopsy, ACID, Biomarker (medicine), 030211 gastroenterology & hepatology, Life Sciences & Biomedicine, Research Article, EXPRESSION, medicine.medical_specialty, NAFLD, non-alcoholic fatty liver disease, NASH, non-alcoholic steatohepatitis, Population, Gastroenterology and Hepatology, SAF, steatosis–activity–fibrosis, VALIDATION, ER, endoplasmic reticulum, 03 medical and health sciences, cDNA, complementary DNA, Internal medicine, ALT, alanine aminotransferase, Gastroenterologi, Internal Medicine, medicine, NAFL, non-alcoholic fatty liver, ALGORITHM, FIB-4, fibrosis-4, education, 030304 developmental biology, PCA, principal component analysis, Science & Technology, Gastroenterology & Hepatology, Hepatology, business.industry, FC, fold change, medicine.disease, digestive system diseases, FLIP, fatty liver inhibition of progression, Ct, cycle threshold, Steatosis, qPCR, quantitative PCR, business

الوصف: Background & Aims Serum microRNA (miRNA) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages. Methods We profiled 2,083 serum miRNAs in a discovery cohort (183 cases with NAFLD representing the complete NAFLD spectrum and 10 population controls). miRNA libraries generated by HTG EdgeSeq were sequenced by Illumina NextSeq. Selected serum miRNAs were profiled in 372 additional cases with NAFLD and 15 population controls by quantitative reverse transcriptase PCR. Results Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen within individual NAFLD stages, but miR-193a-5p consistently showed increased levels in all comparisons. Relative to NAFL/non-alcoholic steatohepatitis (NASH) with mild fibrosis (stage 0/1), 3 miRNAs (miR-193a-5p, miR-378d, and miR378d) were increased in cases with NASH and clinically significant fibrosis (stages 2–4), 7 (miR193a-5p, miR-378d, miR-378e, miR-320b, miR-320c, miR-320d, and miR-320e) increased in cases with NAFLD activity score (NAS) 5–8 compared with lower NAS, and 3 (miR-193a-5p, miR-378d, and miR-378e) increased but 1 (miR-19b-3p) decreased in steatosis, activity, and fibrosis (SAF) activity score 2–4 compared with lower SAF activity. The significant findings for miR-193a-5p were replicated in the additional cohort with NAFLD. Studies in Hep G2 cells showed that following palmitic acid treatment, miR-193a-5p expression decreased significantly. Gene targets for miR-193a-5p were investigated in liver RNAseq data for a case subgroup (n = 80); liver GPX8 levels correlated positively with serum miR-193a-5p. Conclusions Serum miR-193a-5p levels correlate strongly with NAFLD activity grade and fibrosis stage. MiR-193a-5p may have a role in the hepatic response to oxidative stress and is a potential clinically tractable circulating biomarker for progressive NAFLD. Lay summary MicroRNAs (miRNAs) are small pieces of nucleic acid that may turn expression of genes on or off. These molecules can be detected in the blood circulation, and their levels in blood may change in liver disease including non-alcoholic fatty liver disease (NAFLD). To see if we could detect specific miRNA associated with advanced stages of NAFLD, we carried out miRNA sequencing in a group of 183 patients with NAFLD of varying severity together with 10 population controls. We found that a number of miRNAs showed changes, mainly increases, in serum levels but that 1 particular miRNA miR-193a-5p consistently increased. We confirmed this increase in a second group of cases with NAFLD. Measuring this miRNA in a blood sample may be a useful way to determine whether a patient has advanced NAFLD without an invasive liver biopsy.
Graphical abstract
Highlights • Serum miRNA was sequenced in 183 NAFLD cases of varying severity and 10 population controls. • Plasma levels of miR-193a-5p were significantly increased in patients with advanced fibrosis, high NAS scores, or high SAF scores. • Other miRNAs including miR378d and miR378e were also significantly increased in certain comparisons. • The findings for miR-193a-5p were replicated in a cohort of 372 additional NAFLD cases.

وصف الملف: application/pdf; Electronic-eCollection

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1c39a3a5921e0d464a7b2b93c40ef52cTest
https://pure.amc.nl/en/publications/increased-serum-mir193a5p-during-nonalcoholic-fatty-liver-disease-progressionTest(bd6dd66c-d686-4b4d-be46-956a848f1f3b).html

المؤلفون: Stuart McPherson, Marc Herscovitz, Jonathan Vernazza, Quentin M. Anstee, Dina Mansour, Andrea Broad, Paul Cassidy, Allison Grapes

المصدر: JHEP Reports, Vol 3, Iss 4, Pp 100293-(2021)
JHEP Reports

مصطلحات موضوعية: medicine.medical_specialty, NAFLD, non-alcoholic fatty liver disease, Cirrhosis, Transient elastography, EASL, European Association for the Study of the Liver, LFTs, liver function tests, NASH, non-alcoholic steatohepatitis, LSM, liver stiffness measurement, Type 2 diabetes, AST, aspartate aminotransferase, RC799-869, ELF, enhanced liver fibrosis test, Liver disease, T2DM, type 2 diabetes, Diabetes mellitus, Internal medicine, ALT, alanine aminotransferase, Type 2 diabetes mellitus, Internal Medicine, medicine, Immunology and Allergy, GGT, gamma-glutamyl transferase, Non-invasive, Hepatology, medicine.diagnostic_test, ALP, alkaline phosphatase, business.industry, Fatty liver, Gastroenterology, Odds ratio, Serum biomarkers, Diseases of the digestive system. Gastroenterology, medicine.disease, Fibrosis, TE, transient elastography, OR, odds ratio, HbA1c, glycated haemoglobin, Liver function tests, business, HCC, hepatocellular carcinoma, Liver stiffness, Research Article, Non-alcoholic fatty liver disease

الوصف: Background & Aims Individuals with type 2 diabetes (T2DM) are at high risk of developing non-alcoholic fatty liver disease (NAFLD) and advanced fibrosis/cirrhosis. Screening patients with T2DM and normal liver enzymes for NAFLD in primary care remains contentious. Our aim was to develop and assess a primary care pathway integrating two-tier (Fib-4 then transient elastography [TE]) liver fibrosis assessment, irrespective of aetiology, into routine annual review of all patients with T2DM. Methods All patients aged >35 years with T2DM attending annual review at 2 primary care practices in North East England between April 2018 and September 2019 (n = 467) had Fib-4 requested via the electronic patient record. Those with a Fib-4 score above the ‘high-sensitivity’ threshold (>1.3 for ≤65 years and >2.0 for >65 years) underwent TE and were reviewed in secondary care if the liver stiffness measurement (LSM) was >8 kPa. The number of patients identified with advanced disease, service uptake, and predictors of advanced disease were assessed. Results A total of 85/467 (18.5%) patients had raised Fib-4; 27/467(5.8%) were excluded as a result of frailty or known cirrhosis. A total of 58/467 (12.2%) were referred for TE. Twenty-five of 58 (43.1%) had an LSM of >8 kPa and 13/58 (22.4%) had an LSM >15 kPa; 4/58 (6.7%) did not attend and 5/58 (9.3%) had an invalid reading. Twenty of 440 (4.5%) patients were found to have advanced liver disease following specialist review, compared to 3 patients previously identified through standard care (odds ratio [OR] 6.71 [2.0–22.7] p = 0.0022). Alcohol (OR 1.05 [1.02–1.08] p = 0.001) and BMI (OR 1.09 [1.01–1.17] p = 0.021) were predictors of advanced disease, particularly drinking >14/21 units/week (p
Graphical abstract
Highlights • People with type 2 diabetes are at increased risk of advanced liver fibrosis, exacerbated by excess alcohol consumption. • Incorporating a 2-step fibrosis assessment into primary care diabetes review increased advanced fibrosis detection 7-fold. • Fib-4 scores automatically calculated at diabetic review in primary care and results displayed with advisory comments. • Almost half the patients identified with advanced liver disease had alanine transferase below the laboratory cut-off. • This pathway could improve detection of advanced liver disease in individuals with type 2 diabetes in primary care.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1336cef2de43968549cc7d868da73a54Test
http://www.sciencedirect.com/science/article/pii/S2589555921000690Test

المؤلفون: Daniel G.K. Rasmussen, Peder Frederiksen, Diana Julie Leeming, Lise Lotte Gluud, Elisabeth Erhardtsen, Jörn M. Schattenberg, Diane E. Shevell, M.A. Karsdal, Guruprasad P. Aithal

المصدر: Erhardtsen, E, Rasmussen, D G K, Frederiksen, P, Leeming, D J, Shevell, D, Gluud, L L, Karsdal, M A, Aithal, G P & Schattenberg, J M 2021, ' Determining a healthy reference range and factors potentially influencing PRO-C3 – A biomarker of liver fibrosis ', JHEP Reports, vol. 3, no. 4, 100317 . https://doi.org/10.1016/j.jhepr.2021.100317Test
JHEP Reports, Vol 3, Iss 4, Pp 100317-(2021)
JHEP Reports

مصطلحات موضوعية: NASH-CRN, NASH Clinical Research Network, Biopsy, Disease, AST, aspartate aminotransferase, RC799-869, Ethnic groups, Gastroenterology, NIMBLE, Non-Invasive Biomarkers of Metabolic Liver Disease (consortium), Fibrosis, Immunology and Allergy, Body mass index, medicine.diagnostic_test, Fatty liver, NAS, NAFLD Activity Score, Diseases of the digestive system. Gastroenterology, Hospitals, NPV, negative predictive value, Liver biopsy, Biomarker (medicine), Research Article, medicine.medical_specialty, NAFLD, non-alcoholic fatty liver disease, ADAM, A Disintegrin and Metalloproteases, NASH, non-alcoholic steatohepatitis, Reference range, Reference values, AUROC, area under the receiver operating characteristics curve, Internal medicine, ALT, alanine aminotransferase, Internal Medicine, medicine, Humans, FIB-4, fibrosis-4, Healthy volunteers, Hepatology, ALP, alkaline phosphatase, business.industry, CLSI, Clinical and Laboratory Standards Institute, T2DM, type 2 diabetes mellitus, ELF™ test, Enhanced Liver Fibrosis test, medicine.disease, LITMUS, Liver Investigation: Testing Marker Utility in Steatohepatitis (consortium), Collagen type III, PPV, positive predictive value, Reference standards, business, Biomarkers, Non-alcoholic fatty liver disease

الوصف: Background & Aims Progressive fibrosis has been identified as the major predictor of mortality in patients with non-alcoholic fatty liver disease (NAFLD). Several biomarkers are currently being evaluated for their ability to substitute the liver biopsy as the reference standard. Recent clinical studies in NAFLD/NASH patients support the utility of PRO-C3, a marker of type III collagen formation, as a marker for the degree of fibrosis, disease activity, and effect of treatment. Here we establish the healthy reference range, optimal sample handling conditions for both short- and long-term serum storage, and robustness for the PRO-C3 assay. Methods PRO-C3 was measured in 269 healthy volunteers and in 222 NAFLD patients. Robustness of the PRO-C3 assay was measured according to Clinical and Laboratory Standards Institute standards and included validation of interference, precision, and reagent stability, whilst sample stability was defined for storage at different temperatures and for 3 freeze-thaw cycles. Fibrosis scoring was based on histological assessments and used as a reference for the diagnostic ability of PRO-C3 to discriminate between patients with different levels of fibrosis. Results Robustness of the PRO-C3 analysis validated by interference, precision, and reagent stability was found to be within the predefined acceptance criteria. The healthy reference range was determined to be 6.1–14.7 ng/ml. Levels of PRO-C3 were not affected by sex, age, BMI, or ethnicity. Levels of PRO-C3 were able to identify patients with clinically significant fibrosis and advanced fibrosis (AUC = 0.83 (95% CI [0.77–0.88], p
Graphical abstract
Highlights • A normal reference range in healthy adult volunteers was established for PRO-C3. • PRO-C3 levels were not affected by age, sex, BMI, or ethnicity. • PRO-C3 levels increased with liver fibrosis stage. • PRO-C3 identified patients with significant and advanced liver fibrosis.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8d4eefdc7b3714522d884aabf5fb9f2cTest
https://curis.ku.dk/portal/da/publications/determining-a-healthy-reference-range-and-factors-potentially-influencing-proc3--a-biomarker-of-liverTest-fibrosis(c941fd32-bad0-4d92-b259-f5dc9c239ed9).html