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Let-7 miRNA associated with hepatic fibrosis progression in chronic HCV

Circulating plasma levels of the micro RNA let-7 were associated with hepatic fibrosis progression in patients with chronic HCV, according to recent findings published in Hepatology.

“The present study provides evidence that circulating let-7 may serve as a surrogate marker for hepatic fibrosis progression in chronic hepatitis C and suggests a plausible mechanism for this effect,” Harvey J. Alter, MD, in the department of transfusion medicine at the NIH, and colleagues wrote. “To our knowledge, this is the first demonstration of changes in circulating miRNA expression over time during the natural course of chronic HCV infection.”

Although previous studies have identified several circulating micro RNAs (miRNAs) associated with fibrosis progression in chronic HCV, no consistent association has been determined, the researchers wrote.

The current study comprised 130 patients with chronic hepatitis C who were prospectively followed over several decades. Overall, 323 miRNAs were differentially expressed between healthy individuals and patients with chronic hepatitis C, but only six discerned between mild and severe hepatitis. The researchers eventually identified let-7a/7c/7d-5p (let-7) and miR-122-5p as the two best candidates to predict disease progression.

They performed cross-sectional analyses that showed that let-7 was associated with advanced fibrosis, while miR-122-5p was only correlated with inflammatory activity. Further, longitudinal analysis of 60 patients showed that circulating let-7 levels declined as fibrosis declined. However, this did not occur for let-7 levels in the liver. Further, measuring let-7 in extracellular vesicles was not more accurate in predicting fibrosis compared with measuring intact plasma with the fibrosis-4 index. The pathway analysis suggested that the let-7 mechanism could be through activation of transforming growth factor b signaling in hepatic stellate cells.

 

Harvey J. Alter, MD

Source: NIH Clinical Center

“Validation studies in independent cohorts including patients with more advanced hepatic fibrosis are clearly needed,” the researchers wrote. “Even in the absence of clinical use, this study has identified let-7s, more than other miRNAs, as mechanistically important in hepatic fibrosis progression in chronic hepatitis C.” – by Will Offit

Disclosure: The researchers report no relevant financial disclosures.