Plasma Microrna Profile as a Predictor of Early Virological Response to Interferon Treatment in Chronic Hepatitis B Patients

Zhang, Xiaonan; Chen, Cuncun; Wu, Min; Chen, Liang; Zhang, Jiming; Zhang, Xinxin; Zhang, Zhanqin; Wu, Jingdi; Wang, Jiefei; Chen, Xiaorong; Huang, Tao; Chen, Lixiang; Yuan, Zhenghong

doi:10.3851/imp2401

Cited by 32 publications

(41 citation statements)

References 30 publications

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“…Zhang et al showed that a miR profile comprising 11 miRs (hsa-let-7a, hsa-miR-30a, hsa-miR-1290, hsa-miR-106b, hsa-miR-198, hsa-miR-1224-5p, hsamiR-1281, hsa-miR-22, hsa-miR-638 and hsa-let-7f) can predict an initial treatment response (independent association with early virologic response) of IFN in HBV patients. 19 This study showed that there is a potential role of selected miRs in HBV life cycle. MiRs that altered HBsAg/HBeAg secretion were considered to possess HBV modulatory activity.…”

Section: Viral Hepatitismentioning

confidence: 76%

“…While a miR-1281 inhibitor showed the highest potency in inhibiting HBV replication, let-7f, miR-939, and miR-638 were also shown to inhibit viral replication. 19 MiR-939 and miR-638 were also shown to inhibit HBV viral antigen expression in a dose-dependent manner. 19 In a separate study, HBV replication was inhibited by miR-199a-3p, as a consequence of direct interaction of the miR and the HBV coding region.…”

Section: Viral Hepatitismentioning

confidence: 96%

“…19 MiR-939 and miR-638 were also shown to inhibit HBV viral antigen expression in a dose-dependent manner. 19 In a separate study, HBV replication was inhibited by miR-199a-3p, as a consequence of direct interaction of the miR and the HBV coding region. 69 Let-7a, c and f have been reported to be down-regulated in HepG2.2.15 cells that harbor the complete HBV genome and replicate actively by HBx protein.…”

Section: Viral Hepatitismentioning

confidence: 96%

“…18 The liver is a major contributor of circulating miRs and plasma miR levels partially reflect the dynamics of miRs in hepatocytes. 19 Hepatocyte apoptosis and necrosis also release cellular miRs directly into the circulation, explaining the reason for the superior sensitivity of serum miRs when compared to ALT or AST levels in diagnosing liver damage. 20 Bala et al have shown that miR-122 and miR-155 were predominantly associated in protein aggregates in acetaminophen-induced liver necrosis, whereas in alcoholic liver disease associated inflammatory damage, these two miRs were mainly found in the exosome-rich vesicular fraction, suggesting an injuryspecific distribution of miRs in the circulation.…”

mentioning

confidence: 99%

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MicroRNAs in Liver Disease: Bench to Bedside

Shah

Nelson

Kowdley

2013

Journal of Clinical and Experimental Hepatology

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MicroRNAs (miRs) are small non-coding RNAs that negatively regulate gene expression by pairing with partially complementary target sequences in the 3 0 UTRs of mRNAs to promote degradation and/or block translation. Aberrant miR expression is associated with development of multiple diseases including hepatic diseases. The role of miRs in the regulation of gene expression and rapid progress in the field of microRNA research are resulting in momentum toward development of diagnostic markers and novel therapeutic strategies for human liver diseases. Recent studies provide clear evidence that miRs are abundant in the liver and modulate a diverse spectrum of biological functions, thereby supporting an association between alterations of miR homeostasis and pathological liver diseases. Here we review the role of miRs in liver as their physiological and pathological importance has been demonstrated in metabolism, immunity, viral hepatitis, oncogenesis, fatty liver diseases (alcoholic and non-alcoholic), drug-induced liver injury, fibrosis as well as acute liver failure. ( J CLIN EXP HEPATOL 2013;3:231-242)

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Section: Viral Hepatitismentioning

confidence: 76%

Section: Viral Hepatitismentioning

confidence: 96%

Section: Viral Hepatitismentioning

confidence: 96%

mentioning

confidence: 99%

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MicroRNAs in Liver Disease: Bench to Bedside

Shah

Nelson

Kowdley

2013

Journal of Clinical and Experimental Hepatology

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“…Previously, other groups investigated miRNA expression from hepatic FFPE material using real-time PCR from different samples or demonstrating the feasibility of miRNA array experiments from tissue sections [43,44]. Also, FFPE tissue from unguided biopsies from non-cirrhotic non-tumorous liver has been successfully used for array-based miRNA analyses [45]. The novelty in the present study lies in the use of FFPE material from very small ultrasoundguided HCC biopsies of patients under sorafenib therapy, which, to our knowledge, has not been published to date.…”

Section: Discussionmentioning

confidence: 98%

Feasibility of global miRNA analysis from fine-needle biopsy FFPE material in patients with hepatocellular carcinoma treated with sorafenib

et al. 2014

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Sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC). However, the median overall survival (OS) benefit is only ~3 months, and sufficient biomarkers predicting treatment response are not available. The aim of the present study was to evaluate miRNA expression patterns from HCC tissue biopsies as potential biomarkers in patients under sorafenib treatment. Nineteen patients with advanced HCC treated with sorafenib were included. RNA was extracted from formalin-fixed paraffin-embedded (FFPE) liver biopsies. miRNA expression profiling of 818 mature miRNAs was performed using GeneChip® miRNA Array 2.0 (Affymetrix). Global miRNA patterns were assessed using unsupervised hierarchical clustering analysis (UCA), and specific miRNAs with correlation with disease control rate (DCR) or good OS were evaluated by pairwise supervised analyses. UCA divided the patients into three distinct groups by their miRNA expression patterns. However, DCR or OS did not correlate with these sub-groups. We have identified several miRNAs that correlated with either DCR or OS (P<0.05). However, with correction for multiple testing, these results did not reach statistical significance in this small cohort. Global miRNA analysis from very low input RNA deriving from liver biopsies showed distinctive clustering of molecular sub-groups in patients with intermediate and advanced HCC. Clinical response including OS under sorafenib did not correlate with global miRNA expression patterns, but we have identified candidate miRNAs for the prediction of DCR and OS to be evaluated in prospective studies and larger patient cohorts.

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Baseline serum exosome‐derived miRNAs predict HBeAg seroconversion in chronic hepatitis B patients treated with peginterferon

Wang

Zhang

et al. 2021

Journal of Medical Virology

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This study aimed to explore the value of baseline serum exosome‐derived miRNAs for predicting HBeAg seroconversion in chronic hepatitis B (CHB) patients treated with peginterferon (Peg‐IFN). A total of 120 treatment‐naïve HBeAg‐positive CHB patients who received Peg‐IFN therapy (48 weeks) were enrolled. Next‐generation sequencing was performed to screen the serum exosomal miRNAs that were associated with Peg‐IFN treatment outcome, and qRT‐PCR was used to validate them. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the predictive efficacy of biomarkers. Thirty‐three patients (27.5%) achieved HBeAg seroconversion (response group), and 87 patients (72.5%) did not achieve HBeAg seroconversion (nonresponse group). In the identification cohort, 40 serum exosome‐derived miRNAs were differentially expressed between the response group (four patients) and the nonresponse group (four patients). In the confirmation cohort, the expression levels of serum exosomal miR‐194‐5p (p < .001) and miR‐22‐3p (p < .001) were significantly downregulated in the response group (29 patients) compared to the nonresponse group (83 patients). Multivariate analysis identified baseline serum exosomal miR‐194‐5p, miR‐22‐3p, alanine aminotransferase (ALT), and HBV DNA as independent predictors of HBeAg seroconversion (all p < .05). The AUROCs of serum exosomal miRNAs (0.77 and 0.75 for miR‐194‐5p and miR‐22‐3p, respectively) were higher than that of ALT (0.70) and HBV DNA (0.69). The combination of exosomal miR‐194‐5p and miR‐22‐3p further improved the predictive performance with an AUROC of 0.82. Baseline serum exosomal miR‐194‐5p and miR‐22‐3p may serve as novel biomarkers to predict HBeAg seroconversion in CHB patients treated with Peg‐IFN.

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Plasma Microrna Profile as a Predictor of Early Virological Response to Interferon Treatment in Chronic Hepatitis B Patients

Abstract: The 11 microRNA signatures in plasma, together with basic clinical variables, might provide an accurate method to assist in medication decisions and improve the overall sustained response to IFN treatment.

Cited by 32 publications

References 30 publications

MicroRNAs in Liver Disease: Bench to Bedside

MicroRNAs in Liver Disease: Bench to Bedside

Feasibility of global miRNA analysis from fine-needle biopsy FFPE material in patients with hepatocellular carcinoma treated with sorafenib

Baseline serum exosome‐derived miRNAs predict HBeAg seroconversion in chronic hepatitis B patients treated with peginterferon

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