miRNAs in chronic hepatitis B: From potential biomarkers to therapeutic targets

In chapter 2 we showed in a long term follow up of five years, that HBsAg-loss over time is not influenced by either a combination of peg-IFN and adefovir or tenofovir treatment in CHB patients. Although low baseline HBsAg levels can predict HBsAg-loss irrespective of treatment allocation.
In chapter 3 we identified several differentially expressed miRNAs in plasma and liver samples of CHB patients, although there was no overlap between the two entities. This suggests that plasma miRNAs may be used as surrogate biomarkers for viral activity or treatment outcome, whereas liver miRNAs are more likely to be regulated by HBV and could be potential therapeutic targets to control viral activity in the liver.
In chapter 4 we observed in HBeAg positive patients that plasma levels of miR-122-5p and let-7e-5p were correlated with hepatic cccDNA levels, while in HBeAg negative patients miR-200a-3p levels were correlated with HBV transcriptional activity determined by plasma pgRNA/hepatic cccDNA ratio.
In chapter 5 we developed a semi-quantitative assay that detects integrated HBV and mRNA transcripts derived from integrated HBV. We observed that integrated HBV levels are strongly correlated with surrogate markers for virological activity but not to cccDNA levels. The levels of integrated HBV are also predictive for HBsAg-loss.
In chapter 6 we identified one potential novel HBV encoded miRNA in liver samples of CHB patients and demonstrated that expression levels of this miRNA were correlated with plasma HBsAg and hepatic HBV-DNA levels. This suggest that this HBV derived miRNA may play a role in CHB pathogenesis.