Background
MicroRNA-34a (miR-34a) contributes to liver injury through an apoptosis pathway.
Objective
To determine the correlation between serum miR-34a and liver inflammation as assessed by nonalcoholic fatty liver disease (NAFLD) activity score (NAS).
Method
We included a cross-selectional study of 50 patients with NAFLD in this observational study and confirmed diagnosis by liver biopsy, with NAS grading. A control group comprised 23 healthy individuals without chronic liver disease. Serum miR-34a was assayed using a real-time quantitative PCR (Applied Biosystems).
Result
The mean age of NAFLD patients was 46.0 ± 13.7 years, and 52% were female. Metabolic syndrome was found in 76%. Liver histopathology showed that 54% of patients had NAS ≥4 and significant fibrosis (≥2) was found in 22%. Serum levels of miR-34a were significantly correlated with NAS (r = 0.39, P = 0.005), and the degree of steatosis (r = 0.28, P = 0.049), ballooning (r = 0.30, P = 0.034), and fibrosis (r = 0.39, P = 0.005). Serum miR-34a in patients with NAS ≥4 was significantly higher than in those with NAS <4 (P = 0.011) and controls (P < 0.001). There was no significant correlation between serum miR-34a and other variables. The area under receiver operating characteristic curve for serum miR-34a comparing patients with NAS ≥4 and with NAS <4 was 0.67 (95% CI 0.52, 0.82).
Conclusion
Serum level of miR-34a has a significant fair to good correlation with NAS and may serve as a biomarker of liver inflammation and fibrosis in patients with NAFLD.
Interferons play important roles in defense mechanisms against viral infection, and thus interferon therapy has been a standard treatment in chronic hepatitis B patients. Interferons signaling pathways promote interferon-inducible genes including microRNAs. In this research, we aimed to determine microRNAs expression profiles in vitro and in vivo For in vitro model, Huh7 cells were transfected with or without hepatitis B virus plasmid for 6 h, and then treated with 100 ng of pegylated-interferon alpha-2a for 24 h. In vivo, we defined microRNAs expression profiles in pair-liver tissues of chronic hepatitis B patients in comparison between before and after treatment of pegylated-interferon alpha-2a for 48 weeks. Cellular small RNAs were extracted followed by library preparation. To determine microRNAs expression profiles, the next-generation sequencing was carried out on MiSeq platform (Illumina®). In vitro analysis demonstrated that microRNAs can be classified into up-regulated and down-regulated microRNAs in response to hepatitis B virus, interferon, and combination of hepatitis B virus and interferon. Moreover, in vivo analysis revealed microRNAs profiles in non-responders, responders without hepatitis B surface antigen clearance, and responders with hepatitis B surface antigen clearance. The target genes of the candidate microRNAs were determined in terms of roles in cellular pathways and immune response, which might be related to treatment in chronic hepatitis B patients. Results revealed that two down-regulated microRNAs including miR-185-5p and miR-186-5p were correlated in both in vitro and in vivo studies. These two microRNAs might be represented as specific hepatic microRNAs responding to hepatitis B virus and pegylated-interferon alpha-2a treatment, which may remarkable and attractive for further study involving in the association of their target genes and prediction of pegylated-interferon alpha-2a response. Interestingly, microRNAs expression patterns might be useful for understanding the response mechanism and serve as biomarkers for prediction of pegylated-interferon alpha-2a treatment response in patients with chronic hepatitis B.
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