Hepatic disease biomarkers and liver transplantation: what is the potential utility of microRNAs?

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Date: Feb. 2013
Publisher: Expert Reviews Ltd.
Document Type: Report
Length: 10,833 words
Lexile Measure: 1640L

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Author(s): Ricardo C Gehrau 1 , Valeria R Mas 1 , Daniel G Maluf [*] 2

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biomarkers; end-stage liver disease; gene expression; liver transplantation; microarray; microRNA; prediction

The end stage of liver disease caused by chronic or acute hepatic failure, as well as unresectable hepatocellular carcinoma (HCC), represents the principal indications for liver transplantation (LT) as a curative treatment option. Worldwide, LT encompasses approximately 21% of almost 100,000 annual solid organs transplant procedures, whereas 80% of LT activity is concentrated in the US and European regions [1] .

The current global tendency denotes a sustainable increment of LT indications and need in contrast to the unmatched ratio of available liver allografts. The organ shortage trend encourages the proposal to evaluate LT enrolment by strict assessment of candidacy to improve graft allocation and survival rates [1,2] . Important improvements on pre-LT are made possible by continued evolution of the Model of End-Stage Liver Disease as principal priority allocation score established in 2002 [3,4] . Still, further limitations concerning adequate graft allocation, availability and patient survival rates prediction post-LT should be adjusted for Model of End-Stage Liver Disease and alternative score systems [4] . This greatly encourages employing a multidisciplinary assessment before, during, and after LT, and follow-up with the patient to ensure optimal short- and long-term outcomes.

Besides donor and recipient clinical indicators, major efforts are being led to the identification, validation and implementation of accurate diagnostic and prognostic biomarkers in transplantation. In this matter, including LT, the major goal is integral monitoring of the whole LT surgical procedure and post-transplantation course in association with etiological hepatic disease and individual patient characteristics. Numerous molecular biomarkers recently emerged from large experimental proteomic, genomic and genetic settings, although few of these received US FDA approval [5] .

miRNAs have currently gained further attention as potential biomarkers for hepatic disease, injury and disorders, and this is also seen in the LT field. miRNAs are small endogenous noncoding RNAs initially transcribed in the nucleus as stem-loop structures (pri-miRNA). These structures are then recognized by the DROSHA/DGCR8 miRNA-processing multiprotein complex, which cleaves the stem-loop hairpin to generate pre-miRNA, which is then exported to the cytoplasm by exportin-5. Pre-miRNA is processed into a 19-25-nucleotide mature form by Dicer, resulting in a dsRNA molecule. Finally, a single strand is transferred into an argonaute protein [6,7] . miRNAs exert biological roles when they are incorporated into the RNA-induced silencing complex. These small molecules regulate gene expression by specific-sequence mRNA silencing, provoking translation inhibition (partial match) or mRNA degradation (full match) [6-8] . Deregulated expression of miRNA has been further identified in tumor lesions [9] . Despite limited functional understanding in liver development, several reports linked miRNA deregulated expression with hepatic malignancy and liver-associated disease development [8,10] . miRNAs are stable and chemically uniform molecules; features that represent a prerequisite for easy-to-assay biomarkers. Furthermore, the measurable presence of these molecules in body fluids also point to miRNAs as valuable noninvasive biomarkers [11,12] . These features indicate the feasibility of miRNA implementation as biomarkers in LT (Figure 1).

The aim of the present...

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Gale Document Number: GALE|A316900815