Circulating let-7 Levels in Serum Correlate With the Severity of Hepatic Fibrosis in Chronic Hepatitis C

Abstract

Background: Evaluating the progression of hepatic fibrosis in chronic hepatitis C (CHC) is critical, and identifying a predictive biomarker for fibrosis will be helpful for implementing personalized surveillance of hepatocellular carcinoma after the elimination of hepatitis C virus by antiviral therapy. This study aimed to investigate the association of circulating let-7a-5p levels with severity of hepatic fibrosis.

Methods: We analyzed circulating let-7a-5p levels in serum and serum-derived extracellular vesicles (EVs) in 84 Japanese CHC patients who underwent a liver biopsy by quantitative real-time polymerase chain reaction, and investigated the association of its levels with histological hepatic fibrotic stage, liver stiffness, and several hepatic fibrotic markers.

Results: The levels of let-7a-5p in serum and EVs were significantly lower in patients with liver cirrhosis. Additionally, the serum let-7a-5p level correlated significantly with hepatic fibrotic markers, Mac-2 binding protein glycan isomer (M2BPGi), fibrosis-4 (FIB-4) index, aspartate aminotransferase-to-platelet ratio index (APRI), and liver stiffness, evaluated by transient elastography. Furthermore, the serum let-7a-5p level was superior to M2BPGi, FIB-4, and APRI and was comparable to liver stiffness in discriminating liver cirrhosis.

Conclusions: These results provide evidence that circulating let-7a-5p in serum may serve as a surrogate marker for severity of hepatic fibrosis in CHC.

Keywords: extracellular vesicles; hepatic fibrosis; hepatitis C virus; let-7; microRNA.

Figure 1.

Correlations between serum let-7a-5p levels and hepatic fibrosis severity. A, The levels of let-7a-5p in serum were compared between each group using the Mann-Whitney U test. B, Correlations between serum let-7a-5p levels and hepatic fibrotic markers using Spearman’s rank correlation coefficient (rho). Abbreviations: APRI, AST-to-platelet ratio index; AST, aspartate aminotransferase; COI, cutoff index; FIB-4, fibrosis-4; kPa, kilopascals; M2BPGi, Mac-2 binding protein glycan isomer.