HBV may have another virion form in which the nucleic acid is composed of RNA, not DNA. The level of HBV RNA virion in serum may be associated with risk of HBV viral rebound after withdrawal of treatment, and therefore, a potential predictive biomarker to monitor the safe discontinuation of nucleot(s)ide analogues-therapy.

Dysfunction of natural killer (NK) cells has been implicated in the failure of antitumor immune responses in hepatocellular carcinoma (HCC) patients. However, the changes of NK profile in peripheral blood after surgery and tumor tissues of HCC patients, as well as the underlying reason and the significance are vague. Here, we observed that the frequencies of circulating NKG2D+CD56dimNK cells decreased significantly in HBV-related HCC and were negatively correlated with the levels of serum TGF-β and soluble MICA (sMICA). In vitro experiments confirmed that the TGF-β and sMICA in tumor tissue homogenates, as well as sMICA in HCC cells culture supernatants could reduce the frequency of NKG2D+CD56dimNK cells. In addition, in HCC patients the lower frequency of circulating NKG2D+CD56dimNK cells was associated with larger tumor size and/or higher serum GGT. Noticeably, the frequency of NKG2D+CD56dimNK cells at one month after surgery usually failed to restore in early recurrent patients, and that frequency was negatively associated with early recurrence and shorter overall survival. These results suggest that declined frequency of NKG2D+CD56dimNK cells in HCC was associated with higher TGF-β and sMICA production, and low frequency of circulating NKG2D+CD56dimNK cells at one month after surgery may predict poor prognosis of HBV-related HCC patients accepting hepatectomy.

Background and Aim: Dysexpression of circular RNAs has been identified in multiple types of cancer. Hsa_circ_0004018 was reported to be significantly downregulated in hepatocellular carcinoma (HCC) and to display HCC-stage-specific expression features. However, the role of hsa_circ_0004018 in HCC progression remains unclear. Methods: The expression of hsa_circ_0004018 or microRNA-626 (miR-626) was detected in tumor tissues and paired non-tumor tissues from HCC patients, as well as in one normal human liver cell line and 5 HCC cell lines by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, dye exclusion assay, clonogenic assay, scratch migration assay and transwell assay were used to measure cell proliferation and migration capacity, respectively. Luciferase report assay and RNA pull down assay were performed to explore the regulatory effect of certain molecules on the expression of target genes. Results: We found that the expression of hsa_circ_0004018 was lower in tumor tissues than in their paired non-tumor tissues from 28 out of 41 HCC patients. The difference in the expression between tumor tissues and non-tumor tissues was statistically significant (p<0.001). Further analysis revealed that such lower expression in tumor tissues was much more common in bigger tumor size group (≥5cm) compared with the smaller tumor size group (<5cm) (85% vs 42%, p=0.0007). Similarly, hsa_circ_0004018 was downregulated in HCC cell lines. Additionally, a negative correlation between hsa_circ_0004018 and miR-626 expression was noticed in HCC tissues. Moreover, we observed that hsa_circ_0004018 interacted with miR-626/DKK3 and contributed to HCC cell proliferation and migration through inhibiting Wnt/β-catenin signaling pathway in vitro. Furthermore, hsa_circ_0004018 blocked xenograft tumor growth in vivo through inhibiting Wnt/β-catenin signaling pathway by targeting miR-626/DKK3. Conclusion: We revealed that hsa_circ_0004018/miR-626/DKK3 regulatory axis may be a possible novel therapeutic target for HCC.

HIV infection aggravates the progression of liver damage in HCV-coinfected patients, with the underlying pathogenesis being multifactorial. Although high level of oxidative stress has been observed frequently in patients infected with HIV or HCV, the status of oxidative stress in HIV/HCV coinfection and its contribution to HCV liver damage have not been determined. This study involved 363 HBsAg-negative, anti-HCV-positive former blood donors recruited from a village in central China in July 2005; of these, 140 were positive for HIV. Of these 363 subjects, 282 were successfully followed up through July 2009. HIV/HCV-coinfected subjects had higher rates of end-stage liver disease-related death than those monoinfected with HCV. Liver ultrasound manifestations were poor in HIV-positive than in HIV-negative individuals, in both chronic HCV carriers and those with resolved HCV. Serum concentrations of total glutathione (tGSH), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), GSSG, and reduced GSH were higher in HIV-positive than HIV-negative subjects. GSSG concentrations were higher in HIV-infected subjects with abnormal ALT/AST levels than in those with normal ALT/AST levels and were associated with poorer liver ultrasound manifestations. These finding indicated that HIV infection accelerated HCV-associated liver damage in HIV/HCV-coinfected individuals. Increased oxidative stress, induced primarily by HIV coinfection, may contribute to aggravated liver damage.