Correlation Between the Hepatic Expression of Human MicroRNA hsa-miR-125a-5p and the Progression of Fibrosis in Patients With Overt and Occult HBV Infection.

Aims: To evaluate the correlation between the hepatic expression pattern of hsa-miR-125a-5p and HBV-DNA and the progression of fibrosis in patients with overt or occult HBV infection.

Methods: We enrolled all the HBsAg-positive treatment naive patients (overt HBV group) and all the HBsAg-negative patients with hepatocellular carcinoma and with a positive HBV-DNA in their hepatic tissue (occult HBV group), who underwent a diagnostic liver biopsy between April 2007 and April 2015. Tissue concentrations of HBV-DNA and hsa-miR-125a-5p were then analyzed by real-time quantitative PCR. Necroinflammatory activity and fibrosis were evaluated according to the Ishak score.

Results: During the study period, we enrolled 64 patients with overt and 10 patients with occult HBV infection. In the overt HBV group, 35 of 64 (54.7%) showed a mild fibrosis (staging 0-2), 17 (26.6%) a moderate fibrosis (staging 3-4), while the remaining 12 (18.7%) had a cirrhosis. All patients in the occult HBV group were cirrhotic. Patients with more advanced fibrosis stage showed a higher mean age when compared with those with mild ( < 0.00001) or moderate fibrosis ( < 0.00001) and were more frequently male than patients with staging 0-2 ( = 0.04). Similarly, patients with occult B infection were older than HBsAg-positive patients. Liver concentrations of miR-125a-5p were significantly higher in patients with cirrhosis (9.75 ± 4.42 AU) when compared with patients with mild (1.39 ± 0.94,  = 0.0002) or moderate fibrosis (2.43 ± 2.18,  = 0.0006) and were moderately higher in occult than in overt HBV infection ( = 0.09). Moreover, we found an inverse correlation, although not statistically significant, between the tissue HBV-DNA levels and the staging of fibrosis.

Conclusion: This study suggests a correlation between the tissue expression of hsa-miR-125a-5p and the progression of liver damage in a group of patients with occult or overt HBV infection. If confirmed, these data suggest the hsa-miR-125a-5p may be a novel biomarker of hepatic damage.