Diagnosis and staging of HCV associated fibrosis, cirrhosis and hepatocellular carcinoma with target identification for miR-650, 552-3p, 676-3p, 512-5p and 147b

Abstract

BACKGROUND: Chronic HCV infection progresses to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The latter represents the third most common cause for cancer mortality. Currently, there is no reliable non-invasive biomarker for diagnosis of HCV mediated disorders. OBJECTIVE: Profiling expression signature for circulatory miRNAs in the plasma of 167 Egyptian patients (40 healthy, 48 HCV fibrotic, 39 HCV cirrhotic and 40 HCV-HCC cases). METHODS: QRTPCR was used to quantify expression signature for circulatory miRNAs. RESULTS: MiR-676 and miR-650 were powerful in discriminating cirrhotic and late fibrosis from HCC. MiR-650 could distinguish mild (f0-f1) and advanced (f2-f3) fibrosis from HCC cases. MiR-650 and miR-147b could distinguish early fibrosis from healthy controls meanwhile miR-676 and miR-147b could effectively distinguish between mild chronic and (f1-f3) cases from healthy individuals. All studied miRNAs, except miR-512, can differentiate between (f0-f3) cases and healthy controls. Multivariate logistic regression revealed three potential miRNA panels for effective differentiation of HCC, cirrhotic and chronic liver cases. MiR-676-3p and miR-512-5p were significantly correlated in (f1-f3) fibrosis meanwhile miR-676 and miR-512 could differentiate between cirrhosis and (f0-f3) cases. Both miR-650 and miR-512-5p were positively correlated in the cirrhotic group and in (f0-f4) group. Putative targets for investigated miRNAs were also determined. CONCLUSIONS: Investigated miRNAs could assist in staging and diagnosis of HCV associated disorders.

Pathology and Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease-Associated Hepatic Tumors

“…miRNAs are promising diagnostic and prognostic biomarkers that are useful in staging various hepatic disorders that could lead to liver cancer. In particular, circulatory miR-147b, miR-221, miR-512-5p, miR-542, miR-552-3p, miR-650, and miR-676-3p expression profiles are useful biomarkers for the diagnosis and staging of HCV-associated fibrosis, cirrhosis, and HCC [86,87].…”

Assessing Liver Fibrosis Using 2D-SWE Liver Ultrasound Elastography and Dynamic Liver Scintigraphy with 99mTc-mebrofenin: A Comparative Prospective Single-Center Study

“…Many diagnostic assays have at least some value in diagnosing chronic liver disease, including simple laboratory and panel tests, noninvasive scoring systems, circulatory mRNA assays, several imaging modalities, and liver biopsies. Recently, artificial intelligence was also involved evaluating imaging findings and stratifying liver fibrosis [ 44 , 45 , 46 ]. Of note, only a few of these methods are included in clinical guidelines, while others are still competing to find their role in a CLD setting [ 12 , 15 ]…”

Quantitative Assessment of Liver Impairment in Chronic Viral Hepatitis with [99mTc]Tc-Mebrofenin: A Noninvasive Attempt to Stage Viral Hepatitis-Associated Liver Fibrosis

“…Noninvasive serum biomarkers, both patented and freely available, are still lacking precision and are recommended to use only for patients at a high risk of advanced fibrosis, while the goal of the test itself is to rule out liver fibrosis rather than discover it [ 33 , 34 ]. A novel approach using plasma microRNA assays was proven to be capable of staging HBV- and HCV-associated liver fibrosis with high accuracy (AUROC over 80%) [ 35 , 36 ]. Combined microRNA panels were also used and proved as being able to separate significant fibrosis, though the study authors agreed that these findings should be further validated before implementing the method into clinical practice [ 36 ].…”

“…A novel approach using plasma microRNA assays was proven to be capable of staging HBV- and HCV-associated liver fibrosis with high accuracy (AUROC over 80%) [ 35 , 36 ]. Combined microRNA panels were also used and proved as being able to separate significant fibrosis, though the study authors agreed that these findings should be further validated before implementing the method into clinical practice [ 36 ].…”