Performance of Serum microRNAs -122, -192 and -21 as Biomarkers in Patients with Non-Alcoholic Steatohepatitis

Abstract

ObjectivesLiver 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.MethodsSerum 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.ResultsThe 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%).ConclusionsOur 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.

Relation between microRNA‐21, transforming growth factor β and response to treatment among chronic hepatitis C patients

“…They reported that serum miRNA‐21 levels may be related to liver damage activity of HCV. This was in agreement with Bihrer et al and Becker et al, who have found in their studies that miRNA‐21 serum levels strongly correlated with parameters of ongoing liver damage. Additionally, Zhu et al have found that miRNA‐21 was positively correlated with clinical indices in patients with chronic hepatitis C, including viral load, fbrosis, serum alanine aminotransferase, and aspartate aminotransferase.…”

Disease-specific miR-34a as diagnostic marker of non-alcoholic steatohepatitis in a Chinese population

“…In contrast to miR-122, miR-192 has been identified as an oncogene in several cancers, such as colon cancer, breast cancer and gastric cancer[27], and is negatively correlated with the liver metastatic potential of colon cancer cells[28]. Although two independent studies reported increased serum miR-192 levels in NAFLD[12,14], little is known about its function in other liver diseases. Similarly, miR-192 had lower serum levels in NAFLD patients than those of CHB patients, which casts doubt on its diagnostic value in NAFLD.…”

Extracellular vesicles and ceramide: new mediators for macrophage chemotaxis?

“…Circulating EVs have gained much attention in recent years as potential biomarkers in NASH ( 10,11 ). Extensive characterization of serum EVs in animals with NASH led to the discovery of specifi c microRNA signatures with miR-122 and 192 ( 10 ) that was later confi rmed in studies with NASH patients ( 11,12 ). In the current study, for the fi rst time, EVs enriched in C16 ceramide/S1P were found in patients with early NASH.…”