Serum miR-181b-5p predicts ascites onset in patients with compensated cirrhosis

被引:9
作者
Garcia de Paredes, Ana Garcia [1 ]
Villanueva, Candid [2 ,3 ]
Blanco, Carolina [4 ]
Genesca, Joan [3 ,5 ]
Manicardi, Nicolo [6 ]
Carlos Garcia-Pagan, Juan [3 ,7 ]
Luis Calleja, Jose [8 ]
Aracil, Carlos [9 ]
Morillas, Rosa M. [3 ,10 ,11 ]
Poca, Maria [2 ]
Penas, Beatriz [1 ]
Augustin, Salvador [5 ]
Abraldes, Juan G. [7 ,14 ]
Alvarado, Eldimar [2 ]
Royo, Felix [3 ,12 ]
Laura Garcia-Bermejo, Maria [4 ]
Manuel Falcon-Perez, Juan [3 ,12 ]
Banares, Rafael [3 ,13 ]
Bosch, Jaime [3 ,7 ,15 ,16 ]
Gracia-Sancho, Jordi [3 ,6 ]
Albillos, Agustin [1 ,3 ]
机构
[1] Univ Alcala, Hosp Univ Ramon y Cajal, Inst Ramon y Cajal Invest Sanitaria IRYCIS, Gastroenterol & Hepatol Dept, Madrid, Spain
[2] Autonomous Univ Barcelona, Hosp Santa Creu & St Pau, Hosp St Pau Biomed Res Inst IIB St Pau, Barcelona, Spain
[3] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
[4] Inst Ramon y Cajal Invest Sanitaria IRYCIS, Biomarkers & Therapeut Targets Grp, Madrid, Spain
[5] Autonomous Univ Barcelona, Vali dHebron Univ Hosp, Vali dHebron Inst Res VHIR, Liver Unit, Vali dHebron Barcelona Hosp Campus, Barcelona, Spain
[6] IDIBAPS Biomed Res Inst, Liver Vasc Biol Res Grp, Barcelona, Spain
[7] Hosp Clin Barcelona, Inst Digest & Metab Dis, August Pi i Sunyer Inst Biomed Res, Liver Unit,Barcelona Hepat Haemodynam Lab, Barcelona, Spain
[8] Autonomous Univ Madrid, Puerta de Hierro Hosp Res Inst, Hosp Univ Puerta de Hierro, Gastroenterol & Hepatol Dept, Madrid, Spain
[9] Arnau de Vilanova Univ Hosp IRB Lleida, Inst Biomed Res, Lleida, Spain
[10] Hosp Univ Germans Trias i Pujol, Liver Sect, IGTP, Badalona, Spain
[11] Univ Autanoma Barcelona, Barcelona, Spain
[12] Basque Res & Technol Alliance BRTA, Ctr Cooperat Res Biosci CIC BioGUNE, Exosomes Lab, Derio 48160, Bizkaia, Spain
[13] Univ Complutense Madrid, Inst Invest Sanitaria Gregorio Maranon IiSGM, Hosp Univ Gregorio Maranon, Gastroenterol & Hepatol Dept, Madrid, Spain
[14] Univ Alberta, Div Gastroenterol, Liver Unit, Edmonton, AB, Canada
[15] Inselspital Bern, Dept Biomed Res, Bern, Switzerland
[16] Inselspital Bern, Univ Clin Visceral Med & Surg, Bern, Switzerland
关键词
Ascites; beta-blockers; cirrhosis; microRNA; portal hypertension; VENOUS-PRESSURE GRADIENT; PORTAL-HYPERTENSION; MICRORNAS; SURVIVAL;
D O I
10.1016/j.jhepr.2021.100368
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: Treatment with non-selective beta-blockers (NSBBs) reduces the risk of ascites, which is the most common decompensating event in cirrhosis. This study aimed to assess the ability of a serum microRNA (miRNA) signature to predict ascites formation and the hemodynamic response to NSBBs in compensated cirrhosis. Methods: Serum levels of miR-452-5p, miR-429, miR-885-5p, miR-181b-5p, and miR-122-5p were analyzed in patients with compensated cirrhosis (N = 105). Hepatic venous pressure gradient (HVPG) was measured at baseline, after intravenous propranolol, and 1 year after randomization to NSBBs (n = 52) or placebo (n = 53) (PREDESCI trial). miRNAs were analyzed at baseline and at 1 year. Results: Nineteen patients (18%) developed ascites, of whom 17 developed ascites after 1 year. miR-181b-5p levels at 1 year, but not at baseline, were higher in patients that developed ascites. The AUC of miR-181b-5p at 1 year to predict ascites was 0.7 (95% CI 0.59-0.78). miR-429 levels were lower at baseline in acute HVPG responders to NSBBs (AUC 0.65; 95% CI, 0.53-0.76), but levels at baseline and at 1 year were not associated with the HVPG response to NSBBs at 1 year. Conclusions: Serum miR-181b-5p is a promising non-invasive biomarker to identify patients with compensated cirrhosis at risk of ascites development. Lay summary: Ascites marks the transition from the compensated to decompensated stage in cirrhosis and indicates a worsening in prognosis. There are currently no easily accessible tools to identify patients with compensated cirrhosis at risk of developing ascites. We evaluated the levels of novel molecules termed microRNAs in the blood of patients with compensated cirrhosis and observed that miR-181b-5p can predict which patients are going to develop ascites. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).
引用
收藏
页数:6
相关论文
共 19 条
[1]   Value of the hepatic venous pressure gradient to monitor drug therapy for portal hypertension:: A meta-analysis [J].
Albillos, Agustin ;
Banares, Rafael ;
Gonzalez, Monica ;
Ripoll, Cristina ;
Gonzalez, Rosario ;
Catalina, Maria-Vega ;
Molinero, Luis-Miguel .
AMERICAN JOURNAL OF GASTROENTEROLOGY, 2007, 102 (05) :1116-1126
[2]   Profiling circulating microRNAs in patients with cirrhosis and acute-on-chronic liver failure [J].
Blaya, Delia ;
Pose, Elisa ;
Coll, Mar ;
Lozano, Juan Jose ;
Graupera, Isabel ;
Schierwagen, Robert ;
Jansen, Christian ;
Castro, Pedro ;
Fernandez, Sara ;
Sidorova, Julia ;
Vasa-Nicotera, Mariuca ;
Sola, Elsa ;
Caballeria, Joan ;
Trebicka, Jonel ;
Gines, Pere ;
Sancho-Bru, Pau .
JHEP REPORTS, 2021, 3 (02)
[3]   Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases [J].
Chen, Xi ;
Ba, Yi ;
Ma, Lijia ;
Cai, Xing ;
Yin, Yuan ;
Wang, Kehui ;
Guo, Jigang ;
Zhang, Yujing ;
Chen, Jiangning ;
Guo, Xing ;
Li, Qibin ;
Li, Xiaoying ;
Wang, Wenjing ;
Zhang, Yan ;
Wang, Jin ;
Jiang, Xueyuan ;
Xiang, Yang ;
Xu, Chen ;
Zheng, Pingping ;
Zhang, Juanbin ;
Li, Ruiqiang ;
Zhang, Hongjie ;
Shang, Xiaobin ;
Gong, Ting ;
Ning, Guang ;
Wang, Jun ;
Zen, Ke ;
Zhang, Junfeng ;
Zhang, Chen-Yu .
CELL RESEARCH, 2008, 18 (10) :997-1006
[4]   Circulating microRNAs as a Fingerprint for Liver Cirrhosis [J].
Chen, Yan-Jie ;
Zhu, Ji-Min ;
Wu, Hao ;
Fan, Jia ;
Zhou, Jian ;
Hu, Jie ;
Yu, Qian ;
Liu, Tao-Tao ;
Yang, Lei ;
Wu, Chun-Lei ;
Guo, Xiao-Ling ;
Huang, Xiao-Wu ;
Shen, Xi-Zhong .
PLOS ONE, 2013, 8 (06)
[5]   MicroRNA profiles in serum samples from Acute-On-Chronic Liver Failure patients and miR-25-3p as a potential biomarker for survival prediction [J].
Cisilotto, Julia ;
do Amaral, Alex Evangelista ;
Rosolen, Daiane ;
Rode, Michele Patricia ;
Silva, Adny Henrique ;
Winter, Evelyn ;
da Silva, Telma Erotides ;
Fischer, Josiane ;
Matiollo, Camila ;
de Morais Rateke, Elayne Cristina ;
Narciso-Schiavon, Janaina Luz ;
Schiavon, Leonardo de Lucca ;
Creczynski-Pasa, Tania Beatriz .
SCIENTIFIC REPORTS, 2020, 10 (01)
[6]   Natural history and prognostic indicators of survival in cirrhosis: A systematic review of 118 studies [J].
D'Amico, G ;
Garcia-Tsao, G ;
Pagliaro, L .
JOURNAL OF HEPATOLOGY, 2006, 44 (01) :217-231
[7]   Hepatic vein pressure gradient reduction and prevention of variceal bleeding in cirrhosis: A systematic review [J].
D'Amico, Gennaro ;
Garcia-Pagan, Juan Carlos ;
Luca, Angelo ;
Bosch, Jaime .
GASTROENTEROLOGY, 2006, 131 (05) :1611-1624
[8]   MicroRNA-181b Controls Atherosclerosis and Aneurysms Through Regulation of TIMP-3 and Elastin [J].
Di Gregoli, Karina ;
Anuar, Nur Najmi Mohamad ;
Bianco, Rosaria ;
White, Stephen J. ;
Newby, Andrew C. ;
George, Sarah J. ;
Johnson, Jason L. .
CIRCULATION RESEARCH, 2017, 120 (01) :49-+
[9]   Molecular Profiling of Decompensated Cirrhosis by a Novel MicroRNA Signature [J].
Garcia de Paredes, Ana Garcia ;
Manicardi, Nicolo ;
Tellez, Luis ;
Ibanez, Luis ;
Royo, Felix ;
Bermejo, Javier ;
Blanco, Carolina ;
Fondevila, Constantino ;
Fernandez Lanza, Val ;
Garcia-Bermejo, Laura ;
Manuel Falcon-Perez, Juan ;
Banares, Rafael ;
Gracia-Sancho, Jordi ;
Albillos, Agustin .
HEPATOLOGY COMMUNICATIONS, 2021, 5 (02) :309-322
[10]   Time-dependent ROC curves for censored survival data and a diagnostic marker [J].
Heagerty, PJ ;
Lumley, T ;
Pepe, MS .
BIOMETRICS, 2000, 56 (02) :337-344