Circulating exosome DANCR correlated to the recurrence of hepatitis C virus-related hepatocellular carcinoma.

e13688 Background: Long non-coding RNAs (lncRNAs) have been associated with various types of neoplasms. Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) has high risk of recurrence. Methods: Differentially-expressed candidate lncRNAs relevant to HCV-HCC were identified by RNA-seq in Screening set, validated by qPCR in Validation set, and confirmed in external Test cohort. Target lncRNAs in tissue and serum exosome were applied to predict HCC recurrence of HCV-HCC after curative surgical resection in a large Application cohort. Pathogenetic mechanisms of target lncRNA were explored by using JFH1-infectious cells. Results: Of the top ten differentially-expressed lncRNAs relevant to HCV-related HCC identified in Screening set, differentiation antagonizing non-protein coding RNA (DANCR), which was upregulated by HCV infection and identified as the most relevant lncRNA to HCV-HCC, was overexpressed in tumor than in adjacent non-tumor (ANT) tissues. Of 183 HCV-HCC patients followed for 10 years after curative HCC resection, tumor DANCR, tumor/ANT DANCR ratio and circulating exosome DANCR levels were positively associated with HCC recurrence. Circulating exosome DANCR levels by droplet digital PCR provided the best predictive power of HCC recurrence with area under the curve of 0.88, when compared to tumor DANCR levels, tumor/ANT DANCR ratio, and alfa-fetoprotein. Exosome DANCR > 50 copies/ml was the most predictive factor associated with HCC recurrence and mortality (hazard ratio/95% confidence intervals: 7.0/4.3-11.6 and 2.7/1.5-5.1 respectively, Cox regression model). Cell experiments showed that DANCR, positively associated with mesenchymal-associated β-catenin expression, promoted cell migration and invasion ability. Conclusions: lncRNA-DANCR was highly relevant to disease progression of HCV-HCC. Circulating exosome DANCR could serve as a non-invasive prognostic biomarker for HCV-HCC.

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Serum MicroRNAs as Biomarkers in Hepatitis C: Preliminary Evidence of a MicroRNA Panel for the Diagnosis of Hepatocellular Carcinoma

International Journal of Molecular Sciences ◽

10.3390/ijms20040864 ◽

2019 ◽

Vol 20 (4) ◽

pp. 864 ◽

Cited By ~ 8

Author(s):

Anna Weis ◽

Louise Marquart ◽

Diego Calvopina ◽

Berit Genz ◽

Grant Ramm ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis C ◽

Area Under The Curve ◽

Preliminary Evidence ◽

Differentially Expressed ◽

Mild Disease ◽

Qrt Pcr ◽

Reverse Transcription Pcr ◽

Serum Microrna ◽

Serum Micrornas

Early diagnosis of cirrhosis and hepatocellular carcinoma (HCC) due to chronic Hepatitis C (CHC) remain clinical priorities. In this pilot study, we assessed serum microRNA (miRNA) expression to distinguish cirrhosis and HCC, alone and in combination with the aminotransferase-to-platelet ratio (APRI), Fibrosis 4 (FIB-4), and alpha-fetoprotein (AFP). Sixty CHC patients were subdivided into 3 cohorts: Mild disease (fibrosis stage F0-2; n = 20); cirrhosis (n = 20); and cirrhosis with HCC (n = 20). Circulating miRNA signatures were determined using a liver-specific real-time quantitative reverse transcription PCR (qRT-PCR) microarray assessing 372 miRNAs simultaneously. Differentially-expressed miRNA candidates were independently validated using qRT-PCR. Serum miRNA-409-3p was increased in cirrhosis versus mild disease. In HCC versus cirrhosis, miRNA-486-5p was increased, whereas miRNA-122-5p and miRNA-151a-5p were decreased. A logistic regression model-generated panel, consisting of miRNA-122-5p + miRNA-409-3p, distinguished cirrhosis from mild disease (area under the curve, AUC = 0.80; sensitivity = 85%, specificity = 70%; p < 0.001). When combined with FIB-4 or APRI, performance was improved with AUC = 0.89 (p < 0.001) and 0.87 (p < 0.001), respectively. A panel consisting of miRNA-122-5p + miRNA-486-5p + miRNA-142-3p distinguished HCC from cirrhosis (AUC = 0.94; sensitivity = 80%, specificity = 95%; p < 0.001), outperforming AFP (AUC = 0.64, p = 0.065). Serum miRNAs are differentially expressed across the spectrum of disease severity in CHC. MicroRNAs have great potential as diagnostic biomarkers in CHC, particularly in HCC where they outperform the only currently-used biomarker, AFP.

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Molecular Signatures of Recurrent Hepatocellular Carcinoma Secondary to Hepatitis C Virus following Liver Transplantation

Journal of Transplantation ◽

10.1155/2013/878297 ◽

2013 ◽

Vol 2013 ◽

pp. 1-14 ◽

Cited By ~ 4

Author(s):

Trina Das ◽

Deborah L. Diamond ◽

Matthew Yeh ◽

Sajida Hassan ◽

Janine T. Bryan ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Transplantation ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Molecular Mechanisms ◽

Pcr Analysis ◽

Molecular Signatures ◽

Primary Indication ◽

Formalin Fixed Paraffin Embedded ◽

Hcc Recurrence

Chronic hepatitis C virus (HCV) induced hepatocellular carcinoma (HCC) is a primary indication for liver transplantation (LT). In western countries, the estimated rate of HCC recurrence following LT is between 15% and 20% and is a major cause of mortality. Currently, there is no standard method to treat patients who are at high risk for HCC recurrence. The aim of this study was to investigate the molecular signatures underlying HCC recurrence that may lead to future studies on gene regulation contributing to new therapeutic options. Two groups of patients were selected, one including patients with HCV who developed HCC recurrence (HCC-R) ≤3 years from LT and the second group including patients with HCV who did not have recurrent HCC (HCC-NR). Microarray analysis containing more than 29,000 known genes was performed on formalin-fixed-paraffin-embedded (FFPE) liver tissue from explanted livers. Gene expression profiling revealed 194 differentially regulated genes between the two groups. These genes belonged to cellular networks including cell cycle G1/S checkpoint regulators, RAN signaling, chronic myeloid leukemia signaling, molecular mechanisms of cancer, FXR/RXR activation and hepatic cholestasis. A subset of molecular signatures associated with HCC recurrence was found. The expression levels of these genes were validated by quantitative PCR analysis.

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Hepatocellular Carcinoma Recurrence after Hepatitis C Virus Therapy with Direct-Acting Antivirals. A Systematic Review and Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm10081694 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1694

Author(s):

Leonardo Frazzoni ◽

Usama Sikandar ◽

Flavio Metelli ◽

Sinan Sadalla ◽

Giuseppe Mazzella ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Systematic Review ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Meta Analysis ◽

Random Effect ◽

Complete Response ◽

Direct Acting Antivirals ◽

Direct Acting ◽

Hcc Recurrence

Background: Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality among patients with cirrhosis. The risk of HCC recurrence after a complete response among patients treated with direct-acting antivirals (DAAs) has not been fully elucidated yet. Aim: To assess the risk of HCC recurrence after DAA therapy for hepatitis C virus (HCV). Methods: A systematic review across PubMed, Scopus and Scholar up to November 2020, including full-text studies that assessed the pattern of HCC recurrence after DAA therapy for HCV. Random-effect meta-analysis and univariable metaregression were applied to obtain pooled estimates for proportions and relative risk (RR) and variables influential for the outcome, respectively. Results: Thirty-one studies with 2957 patients were included. Overall, 30% (CI, 26–34%) of the patients with a history of HCC experienced HCC recurrence after DAA therapy, at mean time intervals ranging from 4 to 21 months. This result increased when going from European studies (23%, CI, 17–28%) to US studies (34%, CI, 30–38%), to Egyptian studies (37%, CI, 27–47%), and to Asian studies (33%, CI, 27–40%). Sixty-eight percent (CI, 45–91%) of recurrent HCCs developed within 6 months of follow-up since DAA treatment, among the eight studies providing stratified data. Among the studies providing head-to-head comparisons, the HCC recurrence risk was significantly lower after DAA therapy than IFN (RR, 0.64; CI, 0.51–0.81), and after DAA therapy than no intervention (RR, 0.68; CI, 0.49–0.94). Conclusions: The recurrence of HCC after DAA is not negligible, being higher soon after the end of treatment and among non-European countries. DAA therapy seems to reduce the risk of HCC recurrence compared to an IFN regimen and no intervention.

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Hepatitis C Virus and Hepatocellular Carcinoma: Pathogenetic Mechanisms and Impact of Direct-Acting Antivirals

The Open Virology Journal ◽

10.2174/1874357901812010016 ◽

2018 ◽

Vol 12 (1) ◽

pp. 16-25 ◽

Cited By ~ 17

Author(s):

Ivan Schietroma ◽

Giuseppe Corano Scheri ◽

Claudia Pinacchio ◽

Maura Statzu ◽

Arnolfo Petruzziello ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Chronic Infection ◽

The United States ◽

Epidemiological Studies ◽

Direct Acting Antivirals ◽

Direct Acting Antiviral ◽

Direct Acting ◽

Hcc Recurrence

Introduction:Globally, between 64 and 103 million people are chronically infected with Hepatitis C virus (HCV), with more than 4.6 million people in the United States and is associated with more than 15.000 deaths annually. Chronic infection can result in cirrhosis and hepatocellular carcinoma.Explanation:Epidemiological studies have indicated that persistent infection with hepatitis C virus (HCV) is a major risk for the development of hepatocellular carcinoma (HCC), mainly through chronic inflammation, cell deaths, and proliferation. Despite the new direct-acting antiviral drugs (DAA’s) being able to clear the HCV, HCC recurrence rate in these patients is still observed.Conclusion:In this review we highlighted some aspects that could be involved in the onset of HCV-induced HCC such as immune system, viral factors and host genetics factors.Moreover, we focused on some of the last reports about the effects of DAA’s on the HCV clearance and their potential implications in HCC recurrence.

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Co-expression analysis of differentially expressed genes in hepatitis C virus-induced hepatocellular carcinoma

Molecular Medicine Reports ◽

10.3892/mmr.2014.2695 ◽

2014 ◽

Vol 11 (1) ◽

pp. 21-28 ◽

Cited By ~ 2

Author(s):

QINGFENG SONG ◽

CHANG ZHAO ◽

SHENGQIU OU ◽

ZHIBIN MENG ◽

PING KANG ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Differentially Expressed Genes ◽

Expression Analysis ◽

Differentially Expressed

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Impact of Direct Acting Antiviral Therapy for Hepatitis C Virus Infection on Recurrence of Hepatitis C Virus Related Hepatocellular Carcinoma

QJM ◽

10.1093/qjmed/hcaa052.032 ◽

2020 ◽

Vol 113 (Supplement_1) ◽

Author(s):

S M Ghaly ◽

I A Mohamed ◽

N I Musa ◽

O A Ahmed ◽

A S Abuhalima ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Antiviral Therapy ◽

Recurrence Rate ◽

Hcv Infection ◽

Control Group ◽

Direct Acting Antiviral ◽

Direct Acting ◽

Hcc Recurrence

Abstract Background hepatocellular carcinoma is the fifth most common tumor worldwide and the second most common cause of cancer-related death with a male-to-female predominance greater than 2:1. The presence of cirrhosis represents a key risk factor for the development of HCC. The prevalence of cirrhosis among patients with HCC has been estimated to be 85%-95% and the HCC incidence rate among patients with cirrhosis has been shown to be 2%-4% per year. HCV infection is a leading cause of liver cirrhosis and hence the development of HCC. Egypt has the highest HCV prevalence worldwide; with estimated rate of 10% of Egyptians between 15 – 59 years as reported by the Egyptian Health Issues Survey (EHIS) in 2015. Aim of the Work the aim of this study was to evaluate the impact of Direct Acting Antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection on recurrence of HCV related HCC after intervention. Patients and Methods this study was conducted on 50 patients with previously treated HCC who were treated for HCV infection using direct acting antiviral agents after confirming HCC regression and response to different treatment modalities and were followed for one year after antiviral treatment. A control group of another 50 patients with cured HCC who didn’t receive DAA therapy was included in the study to compare the recurrence rate in both groups and its relation to the antiviral therapy. Results the two groups didn’t differ as regards age, sex, biochemical profile, AFP, CBC and child score. The results of the study came to show an HCC recurrence rate of 38% in patients who received direct acting antiviral therapy after HCC intervention versus 62% in those who didn’t receive antiviral therapy. Conclusion direct acting antiviral drugs didn’t show to increase the risk of HCC recurrence in comparison to the control group. Yet it did not abolish it. So, close follow up of patients with HCC receiving antiviral therapy is highly recommended.

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