Identification of Liver and Plasma microRNAs in Chronic Hepatitis B Virus infection

Abstract

Background and AimsWith current standard of care a functional cure for Chronic Hepatitis B (CHB) is only achieved in 1-3% of patients and therefore novel therapies are needed. Disease activity during CHB can be determined by a broad range of virological biomarkers, however these biomarkers are also targets for novel treatment strategies. The aim of this study was to identify novel miRNAs that are differentially expressed in plasma and liver in CHB, and determine whether these miRNAs may serve as biomarkers of disease stage or treatment outcome.MethodsmiRNA Next-Generation-Sequencing of plasma and liver samples from CHB patient and controls was performed to identify differentially expressed miRNAs. The identified candidate miRNAs were validated by qPCR in additional plasma and liver samples from two CHB cohorts.ResultsSeveral miRNAs in plasma and liver were found to be differentially expressed between CHB patients and controls. Of the identified miRNAs expression levels of miR-122-5p in plasma were associated with plasma HBsAg, and plasma and liver HBV-DNA levels. Expression levels of miR-223-3p, miR-144-5p and miR-133a-3p in liver were associated with plasma alanine aminotransferase levels. No correlation was observed between miRNA expression levels at baseline and treatment outcome.ConclusionsLimited overlap between plasma and liver miRNAs was found, indicating that plasma miRNAs could be useful as biomarkers for treatment outcome or viral activity during treatment. Whereas liver miRNAs are more likely to be regulated by HBV and could be potential therapeutic targets to control viral activity in liver.

Hepatitis B Virus and microRNAs: A Bioinformatics Approach

“…In a recent study, HBx upregulated miR-203; as a result, miR-203 downregulated BANF1 and the viral titer was increased in Huh7, Hep G2, and Hep G2.2.15 cells [212]. In other studies, the HBV DNA levels were increased after the overexpression of miR-144-5p and miR-375 in HepG2.2.15 and HepAD38 cells [46].…”

“…In light of the above, it is plain to see that miRNAs may have several clinical implications, ranging from diagnosis and prognosis to treatment development and personalized medicine [40][41][42]. Therefore, in the context of HBV infection, miRNAs may also be considered promising biomarkers because they can be associated with liver health status, the inflammatory process, and the level of HBV replication [43][44][45][46].…”

Circulating Small RNA Profiling of Patients with Alveolar and Cystic Echinococcosis

“…Regarding miR-122-5p and miR-192-5p, they present a liver-enriched expression [63,64], are involved in pathways related to hepatic metabolism and development [28,63], and display altered circulating levels in multiple liver pathologies [27,28,65]. Circulating miR-423-5p and miR-144-5p showed altered levels in patients with Chronic Hepatitis B Virus infection [66]. Finally, miR-150-5p and miR-125a-5p, two miR-NAs related to the regulation of the immune response, were differentially expressed in AE and CE treated patients, respectively.…”

The Connection between MiR-122 and Lymphocytes in Patients Receiving Treatment for Chronic Hepatitis B Virus Infection

“…MicroRNAs are also thought to have a high potential in the evaluation of the response to treatment [26]. MiR-122 is a potential biomarker for the assessment of chronic HBV [26,27], together with viremia and the levels of HBsAg [27]. This makes this microRNA an ideal candidate for the assessment of the response to HBV therapy.…”