Published online Feb 14, 2019. doi: 10.3748/wjg.v25.i6.719
Peer-review started: November 5, 2018
First decision: December 28, 2018
Revised: January 11, 2019
Accepted: January 18, 2019
Article in press: January 18, 2019
Published online: February 14, 2019
Nucleos(t)ide analogues (NAs) only suppress hepatitis B virus (HBV) DNA replication, resulting in decreased serum HBV DNA, but they do not suppress covalently closed circular DNA (cccDNA). Pregenome RNA (pgRNA) is the direct product of cccDNA. A number of studies have shown that HBV RNA levels in serum were related to virological response (VR) and prognosis. However, characteristics of alterations of serum HBV RNA in different chronic hepatitis B (CHB) patients still cannot be fully explained. Whether HBV RNA can predict HBeAg seroconversion is still controversial.
In this work, we investigated the characteristics of HBV RNA alterations in CHB patients with different treatment effects. The relationships of HBV RNA with other serological markers were also analyzed. Finally, we calculated the predictive value of HBV RNA in anticipating HBeAg seroconversion. Solving these problems helps to investigate the predictive value of HBV RNA.
If HBV DNA is maintained at undetectable levels, it is difficult to predict whether a patient will have a serological response. To address this question, we evaluated whether HBV RNA had a relationship with VR and HBeAg antigen seroconversion, how HBV RNA was related to other indicators, whether HBV RNA was an independent indicator of HBeAg seroconversion, and finally, the diagnostic value of HBV RNA.
The present study evaluated 61 CHB patients from September 2006 to December 2007 at the Department of Infectious Diseases of Peking University First Hospital (China) who had begun long-term entecavir (ETV) monotherapy. Finally, we collected 30 treatment-naive individuals. Serum HBV RNA was extracted from 140 μL serum samples at two time points. Then they were reverse transcribed to cDNA with the HBV-specific primer. The product was quantified by real-time quantitative PCR (RT-PCR) using TAMARA probes. Statistical analyses were performed with IBM SPSS 20.0.
By comparing the dynamic characteristics of HBV RNA in the VR and partial VR groups, we found that HBV RNA showed a strong decrease in the VR group. By contrast, HBV RNA increased in the partial VR group. The serum HBV RNA level increased in the HBeAg no-seroconversion group compared with the HBeAg seroconversion group. Overall, HBsAg had a poor correlation with HBV RNA (r = 0.265, P = 0.041), and HBV DNA and HBV RNA did not show a correlation (r = 0.242, P = 0.062). Furthermore, serum HBV RNA was an independent predictor of HBeAg seroconversion and VR. HBeAg seroconversion was more likely to be achieved for CHB patients with HBV RNA levels below 4.12 log10 copies/mL before treatment.
In conclusion, we found that serum HBV RNA predicted both VR and HBeAg seroconversion. The data appeared to suggest that serum HBV RNA decreased in patients who achieved a VR during ETV therapy, and vice versa. Overall, HBsAg and HBV RNA had a poor correlation (r = 0.265, P = 0.041), and HBV DNA had no correlation to HBV RNA (r = 0.242, P = 0.062). Furthermore, serum HBV RNA was an independent predictor of HBeAg seroconversion and VR. HBeAg seroconversion was more likely to be achieved for CHB patients with HBV RNA levels below 4.12 log10 copies/mL before treatment.
The present study suggested that serum HBV RNA decreased in patients who achieved a VR during ETV therapy, and vice versa. HBeAg seroconversion was more likely to be achieved for CHB patients with HBV RNA levels below 4.12 log10 copies/mL before treatment. In the future, the study could focus on the application value of HBV RNA in CHB patients with disease progression.