Circulating MicroRNAs in Patients with Chronic Hepatitis C and Non-Alcoholic Fatty Liver Disease (original) (raw)
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Serum miR-29a and miR-122 as Potential Biomarkers for Non-Alcoholic Fatty Liver Disease (NAFLD)
MicroRNA, 2018
Background: Non-Alcoholic Fatty Liver Disease (NAFLD) is an over accumulation of triglyceride in the liver without alcohol consumption. Its major cause is insulin resistance. Patients with NAFLD can develop liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). MicroRNAs (miR-NAs) are non-coding RNAs that regulate post-transcriptional gene silencing. Previous research reported that miR-29 family (a, b and c) and miR-122 have an important role in regulating insulin resistance related to NAFLD. Objective: The purpose of this study was to investigate that miR-29 and miR-122 can be possible biomarkers for non-invasive diagnosis of NAFLD. Method: Serum samples were collected from 58 NAFLD patients and 34 healthy controls. MiRNAs were extracted from serum by using microRNA purification kit followed by polyuridylation, reverse transcription and quantitative real-time PCR. Also, we analyzed the correlation between miR-29 and miR-122 and level of liver inflammation in NAFLD patients. Results: We found that the serum miR-29a levels in NAFLD patients were significantly lower (P = 0.006) than the control group, while miR-29c levels were unchanged, and miR-29b levels were undetectable. However, we found that serum miR-122 levels in NAFLD patients were significantly higher (P < 0.001) than those found in the control group. For miR-29a, the area under curve (AUC) was 0.679 (P = 0.0065) with 60.87% sensitivity and 82.35% specificity. For miR-122, the AUC was 0.831 (P < 0.0001) with 75.00% sensitivity and 82.35% specificity. Interestingly, the levels of serum miR-122 were significantly different between patients without steatohepatitis (NAS < 4) and steatohepatitis (NAS ≥ 4), indicating that the levels of miR-122 were related to the severity of NAFLD. Conclusion: The levels of miR-29a and miR-122 might be beneficial and compelling as possible biomarkers for non-invasive diagnosis of NAFLD.
Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of diseases from simple stea-tosis to non-alcoholic steatohepatitis, with approximately 20% risk of progressing to fibrosis and cirrhosis. The aim of this study was to compare the relative expression levels of circulating miR-21, miR-34a, miR-122, miR-125b and miR-375 between healthy controls and NAFLD patients, and to assess the feasibility of microRNAs as potential biomarkers for NAFLD. A cross-sectional study was conducted to evaluate circulating serum miRNAs as potential diagnostic markers for NAFLD. Twenty-eight clinically diagnosed and histologi-cally-confirmed NAFLD patients, as well as 36 healthy controls were enrolled in this study. The relative expression of serum microRNAs were calculated using the comparative cycle threshold with spiked-in C. elegans miR-39 as exogenous internal control. Serum levels of miR-34a and miR-122 were significantly higher in NAFLD patients than in healthy controls (P = <0.0001). Positive correlations were observed between serum miR-34a with very low density lipoprotein cholesterol (VLDL-C) and triglyceride levels. However, the expression levels of miR-34a and miR-122 did not correlate with the histological features of NAFLD. Interestingly, receiver operating characteristic (ROC) curve analysis revealed that miR-34a and miR-122 are potential markers for discriminating NAFLD patients from healthy controls with an area under the curve (AUC) values of 0.781 and 0.858, respectively. Serum levels of miR-34a and miR-122 were found to be significantly higher among NAFLD patients, and were positively correlated with VLDL-C and triglyceride levels. Thus, circulating miR-34a and miR-122 can be used as potential biomarkers for discriminating NAFLD patients from healthy controls. Larger cohorts are required to validate the utility of miR-34a and miR-122 in monitoring liver injury.
JHEP Reports, 2021
Background & Aims: Serum microRNAs (miRNAs) levels are known to change in nonalcoholic 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 NAFLD cases 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 NAFLD cases and 15 population controls by quantitative reverse transcriptase-polymerase chain reaction. Results: Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen within individual NAFLD stages but miR-193a-5p consistently the showed increased levels in all comparisons. Relative to NAFL/NASH with mild fibrosis (stage 0/1), three miRNAs (miR-193a-5p, miR-378d and miR378d) were increased in cases with NASH and clinically significant fibrosis (stage 2-4), seven (miR193a-5p, miR-378d, miR-378e, miR-320b, c, d & e) increased in cases with NAFLD Activity Score (NAS) 5-8 compared with lower NAS, and three (miR-193a-5p, miR-378d, miR-378e) increased but one (miR-19b-3p) decreased in steatosis, activity, and fibrosis "activity" (SAF-A) score 2-4 compared with lower SAF-A. The significant findings for miR-193a-5p were replicated in the additional NAFLD cohort. 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.
Significance of MiRNA-34a and MiRNA-192 as a risk factor for nonalcoholic fatty liver disease
Journal of Genetic Engineering and Biotechnology
Background and aims NAFLD is one of the fast-growing health problems that affects up to 25% of people worldwide. Numerous miRNAs have been clarified as important regulators of liver pathophysiology, including NAFLD. Thus, we investigated the expression of the MiRNA-34a and MiRNA-192 as diagnostic markers for NAFLD. Patients and methods Blood samples were collected from NAFLD cases and healthy controls. The expression profile of both studied miRNAs was detected via real-time PCR analysis. Results The present study showed that both studied miRNAs were upregulated in NAFLD patients compared to controls. Interestingly, miRNA-34a and MiRNA-192 are upregulated in NAFLD patients with early fibrosis compared to controls [with a fold change of 4.02 ± 11.49 (P = 0.05) and 18.43 ± 47.8 (P = 0.017), respectively]. However, miRNA-34a is downregulated in NAFLD patients with advanced fibrosis compared to controls, with fold expression of 0.65 ± 1.17 (P = 0.831). The area under the receiver operati...
Circulating microRNAs in patients with non-alcoholic fatty liver disease
World journal of hepatology, 2014
To identify novel non-invasive biomarkers for non-alcoholic fatty liver disease (NAFLD). Twenty patients with histologically proven NAFLD and 20 controls were included. All NAFLD cases were scored using the NAFLD activity score. The relative expressions of miR-197, miR-146b, miR-10b, miR-181d, miR-34a, miR-122, miR-99a and miR-29a were analyzed using real-time polymerase chain reaction. Serum levels of miR-181d, miR-99a, miR-197 and miR-146b were significantly lower in biopsy-proven NAFLD patients than in the healthy controls. Serum levels of miR-197 and miR-10b were inversely correlated with degree of inflammation and miR-181d and miR-99a were inversely correlated with serum gamma glutamyl transferase levels in non-alcoholic steatohepatitis patients. NAFLD is associated with altered serum miRNA expression pattern. This study provides clues for defining the non-invasive diagnosis of NAFLD.
Electronic physician, 2016
Introduction: Liver fibrosis is the excessive accumulation of extracellular matrix that occurs by activation of hepatic stellate cells (HSCs), which has been identified as the major driver of liver fibrosis. Several studies confirmed that miRNAs have regulatory effects on the activation of HSCs by affecting the signaling pathways. The aim of this study was to develop non-invasive diagnostic markers by measuring different circulating miRNAs in serum as predictor markers for early diagnosis of liver fibrosis and its progression. Methods: In this case-control study, we enrolled 66 subjects with chronic hepatitis C (CHC) with early stage of fibrosis and 65 subjects with CHC with late-stage fibrosis. Also, 40 subjects were included as normal controls. The six main miRNAs, i.e., miR-138, miR-140, miR-143, miR-325, miR-328, and miR-349, were measured using the reverse transcription-polymerase chain reaction. Results: In the cases of CHC both with early and late stage of fibrosis, the circulating levels of the six main miRNAs were significantly higher than the levels in the control group. ROC analysis indicated that the sensitivity and specificity of miR-138 were 89.3% and 71.43%, respectively, in the early stage of fibrosis. In the late stage, the sensitivity and specificity of miR-138 were 89.3 and 93.02%, respectively, whereas, for miR-143, they were 75.0 and 88.4%, respectively. Conclusions: Circulating miR-138 could serve as a non-invasive biomarker for the detection of early fibrosis. Also, miR-138 and miR-143 could be specific biomarkers for indicating the late stage of liver fibrosis.
Serum microRNA-34a is potential biomarker for inflammation in nonalcoholic fatty liver disease
Asian Biomedicine
Background MicroRNA-34a (miR-34a) contributes to liver injury through an apoptosis pathway. Objective To determine the correlation between serum miR-34a and liver inflammation as assessed by nonalcoholic fatty liver disease (NAFLD) activity score (NAS). Method We included a cross-selectional study of 50 patients with NAFLD in this observational study and confirmed diagnosis by liver biopsy, with NAS grading. A control group comprised 23 healthy individuals without chronic liver disease. Serum miR-34a was assayed using a real-time quantitative PCR (Applied Biosystems). Result The mean age of NAFLD patients was 46.0 ± 13.7 years, and 52% were female. Metabolic syndrome was found in 76%. Liver histopathology showed that 54% of patients had NAS ≥4 and significant fibrosis (≥2) was found in 22%. Serum levels of miR-34a were significantly correlated with NAS (r = 0.39, P = 0.005), and the degree of steatosis (r = 0.28, P = 0.049), ballooning (r = 0.30, P = 0.034), and fibrosis (r = 0.39, ...
American Journal of Gastroenterology, 2011
The liver contains large amounts of microRNA-22 (miR-22), whereas other tissues contain only marginal amounts of this miRNA. MicroRNAs have also been found to circulate in the blood in a cell-free form; their potential as readily accessible disease markers is currently evaluated. Here, we investigated if the serum levels of miR-22 might be useful as disease parameter in patients with chronic hepatitis C virus (HCV) infection.
Correlation Between miR-125b Expression and Liver Fibrosis in Patients with Chronic Hepatitis C
Hepatitis Monthly, 2019
Objectives: The study aimed to investigate the role of miR-125b as a non-invasive biomarker in chronic hepatitis C. Methods: An observational study was conducted on 94 treatment-naïve HCV-infected patients (mean age 49.8 ± 11.5 years, 59.6% females). Liver fibrosis was assessed by transient elastography (TE) and the expression of miR-125b in plasma was quantified by real-time PCR. Results: All patients were infected with HCV genotype 1b and had active viral replication, 42.6% had significant cytolysis, and 73.4% had increased serum gamma-glutamyl transferase (GGT) values. Significant fibrosis (liver stiffness measured by TE of > 7.1 kPa) was present in 61.7% of the patients. No significant associations were found between miR-125b expression and baseline HCV viral load (P = 0.56), IL28B polymorphisms (P = 0.5), alpha-fetoprotein levels (P = 0.27), and patients' gender (P = 0.13) or age (P = 0.5). In a univariate analysis, the miR-125b expression level was significantly correlated with ALT (P = 0.001) and GGT levels (P < 0.0001). An up-regulated expression of miR-125b was found in plasma samples from patients with advanced liver fibrosis as compared to those with mild/moderate fibrosis [mean miR-125b value = 0.002 versus 0.001 (P = 0.02)]. In a multiple regression analysis, an upregulated miR-125b expression level remained independently in association only with significant fibrosis and increased GGT level (P = 0.026; R 2 = 0.242). Conclusions: An up-regulated miR-125b expression might be an indicator of severe liver fibrosis in patients with chronic hepatitis C, independent of the viral replication level.
Elevated miR-33a and miR-224 in steatotic chronic hepatitis C liver biopsies
World journal of gastroenterology : WJG, 2014
To assess the expression of selected microRNAs (miRNA) in hepatitis C, steatotic hepatitis C, noninfected steatotic and normal liver tissues. The relative expression levels of miR-21, miR-33a, miR-96, miR-122, miR-125b, miR-221 and miR-224 were determined in 76 RNA samples isolated from 18 non-steatotic and 28 steatotic chronic hepatitis C (CHC and CHC-Steatosis, respectively) cases, 18 non-infected, steatotic liver biopsies of metabolic origin (Steatosis) and 12 normal formalin-fixed paraffin-embedded liver tissues using TaqMan MicroRNA Assays. All CHC biopsy samples were obtained prior to initiating therapy. Patients' serum biochemical values, which included glucose, triglyceride, cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl-transferase (GGT), alkaline phosphatase (AP), were obtained and correlated with relative miRNA expression. When compared with control non-infected liver samples, miR-122 and miR-221 levels were reduced in CH...