Document Detail


Distinct microRNA profiles are associated with the severity of hepatitis C virus recurrence and acute cellular rejection after liver transplantation.
MedLine Citation:
PMID:  23408392     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recurrent hepatitis C virus (HCV) infection is associated with accelerated fibrosis rates after liver transplantation (LT) and is the leading cause of graft failure. Furthermore, distinguishing recurrent HCV from acute cellular rejection (ACR) can be problematic, and this can lead to inappropriate treatments and adverse outcomes. We hypothesized that intragraft microRNA (miRNA) expression profiles could distinguish the severity of recurrent HCV and differentiate recurrent HCV from ACR. We established meticulously matched post-LT patient cohorts in order to derive robust global miRNA expression profiles and minimize the impact of variables known to influence HCV recurrence. These cohorts consisted of patients with slow HCV fibrosis progression (Ishak stage < F2), fast HCV fibrosis progression (Ishak stage ≥ F2), ACR, and nonviral etiologies. We found increased intragraft expression of miRNA-146a, miRNA-19a, miRNA-20a, and miRNA-let7e in slow progressors versus fast progressors, and we validated these findings with quantitative PCR. This miRNA network regulates the expression of cardinal genes implicated in promoting antifibrogenic, antiangiogenic, and anti-inflammatory pathways. miRNA-19a and miRNA-20a were also specifically detected in the serum of slow progressors. Furthermore, intragraft miRNA expression distinguished fast HCV progression from ACR. Here, changes in the expression of key miRNAs regulating fibrogenic and angiogenic pathways were associated with fast HCV progression. We demonstrate specific miRNA expression signatures that discriminate the rates of fibrosis progression in patients with recurrent HCV, and we distinguish recurrent HCV from ACR after LT. A pathway analysis indicates that specific miRNAs may play a regulatory role in these processes. Selected miRNAs may serve as intragraft and serum biomarkers for recurrent HCV after LT and help to distinguish between ACR and recurrent HCV.
Authors:
Deepak Joshi; Siamak Salehi; Helen Brereton; Matthew Arno; Alberto Quaglia; Nigel Heaton; John O'Grady; Kosh Agarwal; Varuna Aluvihare
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-03-22
Journal Detail:
Title:  Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society     Volume:  19     ISSN:  1527-6473     ISO Abbreviation:  Liver Transpl.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-28     Completed Date:  2013-09-13     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  100909185     Medline TA:  Liver Transpl     Country:  United States    
Other Details:
Languages:  eng     Pagination:  383-94     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 American Association for the Study of Liver Diseases.
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MeSH Terms
Descriptor/Qualifier:
Adult
Biopsy
Chi-Square Distribution
Diagnosis, Differential
Disease Progression
Female
Gene Expression Profiling / methods
Gene Regulatory Networks
Genetic Markers
Genetic Testing / methods
Graft Rejection / diagnosis,  genetics*,  immunology
Hepatitis C / complications,  diagnosis,  genetics*
Humans
Immunity, Cellular / genetics*
Liver / immunology,  metabolism*,  pathology,  virology
Liver Cirrhosis / diagnosis,  genetics*,  surgery*,  virology
Liver Transplantation / adverse effects*,  immunology
Male
MicroRNAs / metabolism*
Middle Aged
Oligonucleotide Array Sequence Analysis
Predictive Value of Tests
Real-Time Polymerase Chain Reaction
Recurrence
Reproducibility of Results
Severity of Illness Index
Time Factors
Treatment Outcome
Virus Activation / genetics*
Grant Support
ID/Acronym/Agency:
MR/J006742/1//Medical Research Council
Chemical
Reg. No./Substance:
0/Genetic Markers; 0/MicroRNAs
Comments/Corrections
Comment In:
Liver Transpl. 2013 Apr;19(4):355-7   [PMID:  23447337 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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