Differential expression profile of hepatic circular RNAs in chronic hepatitis B.

CircRNAs exert gene regulatory effects by sequestering target microRNAs (miRNAs) and play a vital role in the onset and development of disease. Until recently, little has been known about the expression, regulation and biological function of circRNAs in both health and chronic hepatitis B (CHB).To identify hepatic circRNAs associated with CHB, we performed RNA sequencing using liver biopsies from untreated CHB patients and controls. We then established a bioinformatics pipeline for identification of CHB-associated circRNAs and in silico analysis of the circRNA-miRNA-mRNA pathways. We used quantitative reverse transcription polymerase chain reaction (qRT-PCR) to confirm these results. The profiles of hepatic circRNA expression were significantly different in CHB compared with controls, with a total of 99 dysregulated circRNAs identified to be correlated with CHB. Computational analysis of the circRNA-miRNA-mRNA pathways revealed a large number of miRNAs (665), which were putatively targeted by the differentially expressed hepatic circRNAs. Interestingly, four of the predicted CHB-related circRNA-miRNA-mRNA pathways were found to be involved in the pathogenesis of HBV infection and progression of HBV-associated liver disease. Among these pathways, regression analysis of gene expression revealed a strong positive correlation between hsa_circ_0000650 and TGFß2 and a negative correlation between hsa_circ_0000650 and miR-6873-3p, which hinted that hsa_circ_0000650 interacted with TGFß2 mediated by miR-6873-3p. This study firstly demonstrates that patients with CHB present different profiles of hepatic circRNAs and circRNA/miRNA interactions. Thus, circRNAs have promise as novel mechanisms underlying the pathogenesis and progression of CHB.

Systematic review and meta-analysis: Development of hepatocellular carcinoma in chronic hepatitis B patients with hepatitis e antigen seroconversion.

Hepatitis B e antigen (HBeAg) seroconversion is considered to have significantly favourable clinical outcomes for patients with chronic hepatitis B (CHB). However, inconsistent study results suggest that hepatocellular carcinoma (HCC) still occurs in patients with HBeAg seroconversion. We performed a systematic review and meta-analysis to determine the incidence of HCC in patients with CHB after HBeAg seroconversion. Web of Science, PubMed and Embase databases were searched through January 2017. The incidence of HCC in CHB patients after HBeAg seroconversion was pooled using a random-effects model or fix-effects model. Sixteen studies were finally included, involving 4910 patients with HBeAg seroconversion. The overall pooled proportion suggested that 3.33% (95% confidence interval (CI): 2.28%-4.58%) of patients with CHB develop HCC despite HBeAg seroconversion. In patients with HBeAg seroconversion without cirrhosis, the pooled proportion of HCC development was 0.94% (95% CI: 0.15%-2.4%). Moreover, patients with cirrhosis, active hepatitis, or aged greater than 40 years at the time of HBeAg seroconversion were at significantly higher risk for HCC development. HBeAg seroconversion was significantly associated with a reduced risk of HCC compared with persistently positive HBeAg (RR = 0.58, 95% CI: 0.35-0.97, P = .04). Despite the reduced risk with HBeAg seroconversion, HCC can still occur in a proportion of patients with CHB after HBeAg seroconversion. Long-term monitoring is needed for patients with established cirrhosis, active hepatitis or those older than 40 years at the time of HBeAg seroconversion.