MicroRNA-based diagnostic tools for advanced fibrosis and cirrhosis in patients with chronic hepatitis B and C

Appourchaux, Kevin; Dokmak, Safi; Resche-Rigon, Matthieu; Tréton, Xavier; Lapalus, Martine; Gattolliat, Charles-Henry; Porchet, Emmanuelle; Martinot–Peignoux, Michelle; Boyer, Nathalie; Vidaud, Michel; Bédossa, Pierre; Marcellin, Patrick; Bièche, Ivan; Estrabaud, Emilie; Asselah, Tarik

doi:10.1038/srep34935

Cited by 47 publications

(48 citation statements)

References 61 publications

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“…Diagnostic tools are under development to better diagnose advanced fibrosis. 82 Patients with advanced cirrhosis will require continued care despite viral cure. The risk of HCC in patients with cirrhosis is reduced but not eliminated; patients treated with DAAs should continue to be closely monitored for HCC (ultrasound every six months).…”

Section: Key Pointmentioning

confidence: 99%

Eliminating hepatitis C within low-income countries – The need to cure genotypes 4, 5, 6

Asselah

Hassanein

Waked³

et al. 2018

Journal of Hepatology

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Around 70 to 100 million people are chronically infected with HCV worldwide. HCV antiviral drug development has revolutionised the treatment of HCV, with several direct-acting antiviral agents offering patients the chance of cure after only 8-12 weeks of treatment. Drug development was initially focussed on HCV genotype 1 (GT1) infection, since this was the most prevalent worldwide, although clinical trials included all genotypes prevalent in the US and Europe. Because the earliest in vitro assays utilised the GT1b and 2 replicons, the initial classes of direct-acting antivirals (protease inhibitors, non-nucleotide polymerase inhibitors) were GT1-specific, albeit they had an effect on other less prevalent genotypes. Epidemiological data has shown the regional importance of other HCV genotypes. More than 50% of all HCV infections around the globe are not with GT1. The prevalence of HCV genotype 4 (GT4), 5 (GT5), and 6 (GT6) is increasing in North America and Europe due to migration from the Middle East, Africa and South-East Asia. With the successful development of the multi and pan-genotypic non-structural protein 5A inhibitors, second generation protease inhibitors and nucleotide non-structural protein 5B inhibitors comes a unique opportunity to achieve global HCV elimination. The goal of this review is to summarise the available information pertaining to GT4, GT5 and GT6, with a specific focus on direct-acting antiviral agents.

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Section: Key Pointmentioning

confidence: 99%

Eliminating hepatitis C within low-income countries – The need to cure genotypes 4, 5, 6

Asselah

Hassanein

Waked³

et al. 2018

Journal of Hepatology

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“…Therefore, the present study aimed to investigate the potential of circulating miRNAs as a method of diagnosis. Circulating miRNAs, as diagnostic markers for different stages of hepatic fibrosis, have been extensively studied in previous years (6,(25)(26)(27). miRNAs are derived from blood or body fluids, making them easily accessible as potential biomarkers for the evaluation of hepatic fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Plasma microRNA: A novel non‑invasive biomarker for HBV‑associated liver fibrosis staging

et al. 2018

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The aim of the present study was to evaluate the potential use of 7 plasma miRNAs for liver fibrosis staging in patients with chronic hepatitis B virus (HBV) infection. Relative levels of miRNAs were measured using quantitative polymerase chain reaction and used to develop a diagnostic panel. A receiver operating characteristic (ROC) curve was drawn to evaluate the performance of individual miRNAs and the whole panel. It was identified that hsa-miR-122 exhibited significantly different expression levels between F4 and F3, F2, F1, and F0 fibrosis stages (P<0.05), and between F2 and F1 stages (P= 0.045); hsa-miR-146a-5p, hsa-miR-29c-3p and hsa-miR-223 exhibited significantly different expression levels between F4 and F0 stages. ROC analysis revealed that hsa-miR-122-5p, hsa-miR-223 and hsa-miR-29c-3p identified patients with ≥F2 fibrosis with area under the curve (AUC) = 0.745, 0.631 and 0.670, respectively. hsa-miR-122-5p identified patients with ≥F3 disease (AUC= 0.783). hsa-miR-122-5p, hsa-miR-223 and hsa-miR-29c-3p identified patients with cirrhosis with AUC= 0.776, 0.617 and 0.619, respectively. The miRNA panel exhibited a higher accuracy compared with individual miRNAs in discriminating between ≥F2, ≥F3 and F4 fibrosis stages with AUC= 0.904, 0.889 and 0.835, respectively. hsa-miR-122-5p, hsa-miR-146a, hsa-miR-29c and hsa-miR-223 were positively correlated with fibrosis stage. hsa-miR-122-5p and hsa-miR-381-3p were negatively correlated with alanine aminotransferase, aspartate transaminase and HBV viral DNA load. These 7 miRNAs may serve as potential biomarkers of liver fibrosis in patients with HBV-associated fibrosis. The miRNA panel may serve as a novel non-invasive method for liver fibrosis staging.

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“…In another study, the expression of 13 fibrosis‐related microRNAs (miRNAs; miR‐20a, miR‐21, miR‐27a, miR‐27b, miR‐29a, miR‐29c, miR‐92a, miR‐122, miR‐146a, miR‐155, miR‐221, miR‐222 and miR‐224) was analysed in 194 serums and 177 liver biopsies of patients with either CHB or chronic hepatitis C (CHC) to develop models to diagnose advanced fibrosis and cirrhosis (Metavir F3‐F4) . In CHB subjects, the model (serum miR‐122, serum miR‐222, platelet count and alkaline phosphatase) was more accurate than APRI and FIB‐4 to discriminate in between mild and moderate fibrosis (F1‐F2) and F3‐F4 (AUC of CHB model: 0.85 vs APRI: 0.70 and FIB‐4: 0.81).…”

Section: Who To Treat: the Importance Of Fibrosis As Prognosis Factormentioning

confidence: 99%

Towards HBV curative therapies

Schinazi

Ehteshami

Bassit

et al. 2018

Liver International

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Tremendous progress has been made over the last 2 decades to discover and develop approaches to control hepatitis B virus (HBV) infections and to prevent the development of hepatocellular carcinoma using various interferons and small molecules as antiviral agents. However, none of these agents have significant impact on eliminating HBV from infected cells. Currently the emphasis is on silencing or eliminating cccDNA, which could lead to a cure for HBV. Various approaches are being developed including the development of capsid effectors, CRISPR/Cas9, TALENS, siRNA, entry and secretion inhibitors, as well as immunological approaches. It is very likely that a combination of these modalities will need to be employed to successfully eliminate HBV or prevent virus rebound on discontinuation of therapy. In the next 5 years clinical data will emerge which will provide insight on the safety and feasibility of these approaches and if they can be applied to eradicate HBV infections globally. In this review, we summarize current treatments and we highlight and examine recent therapeutic strategies that are currently being evaluated at the preclinical and clinical stage. K E Y W O R D Santiviral agents, cccDNA, HBV cure, immunotherapy

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MicroRNA-based diagnostic tools for advanced fibrosis and cirrhosis in patients with chronic hepatitis B and C

Cited by 47 publications

References 61 publications

Eliminating hepatitis C within low-income countries – The need to cure genotypes 4, 5, 6

Eliminating hepatitis C within low-income countries – The need to cure genotypes 4, 5, 6

Plasma microRNA: A novel non‑invasive biomarker for HBV‑associated liver fibrosis staging

Towards HBV curative therapies

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