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methods can be used to detect and quantify HBV RNA. As the widely accepted standardized method for
HBV RNA detection is not available, further studies are needed to develop a more accurate and reliable
technique of HBV RNA detection and quantification.

FUTURE STRATEGY ON HBV RNA
Before HBV RNA can be applied as a biomarker in clinic for CHB patients on a large scale, there are still
many questions that need to be solved. Firstly, the methodology for detecting and quantifying serum
HBV RNA should be standardized to make it possible that the results of different studies are comparable.
Secondly, more clinical and molecular biology research is needed to further clarify details dynamics of HBV
RNA under different conditions in CHB patients, for example, different HBV replication states, different
stages of CHB, and receiving what kind of antiviral drugs, NAs therapy or interferon therapy. Thirdly, more
studies should focus on detecting HBV RNA among different ethnic groups and genotypes of CHB patients.
Moreover, further and more exploration should be made to illuminate the correlation between HBV RNA
and hepatocarcinogenesis.

CONCLUSION
In this review, we summarized the current progress and knowledge on the role of HBV RNA in HBV
replication and pathogenicity. As mentioned above, HBV RNA may reflect the activity of intrahepatic
cccDNA, even in CHB patients whose HBV DNA is maintained at low or undetectable levels through
long-term antiviral therapy. And HBV RNA might play an important role in viral replication, promoting
cirrhosis, and hepatocarcinogenesis. Moreover, serum HBV RNA has the potential of evaluating the efficacy
of anti-viral drugs and predicting safe discontinuation of NA-therapy. And the intrahepatic HBV pgRNA
could be used for assessing the prognosis of HCC. Therefore, HBV RNA possesses great potentials to be
a new surrogate or complementary biomarker for HBV DNA in CHB patients. However, more research
concerning the molecular biology of HBV RNA and more multi-centered and large-scale cohort studies
should be conducted to assess and testify the feasibility and safety of HBV RNA as a novel biomarker for
CHB in the future. Moreover, better understanding of HBV RNA will also provide new methods and
strategies for anti-HBV therapy.

DECLARATIONS
Authors’ contributions
Contributed the central idea and wrote the initial draft of this paper: Ding WB
Refining the ideas, carrying out the editing, revision, and finalizing of the manuscript: Zhou WP, Yang F
Discussed the ideas and did the literature research: Wang MC, Zhang JN, Sun DP, Dong JP
Writing and revisions of the manuscript: All authors

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was supported by National Key Basic Research Program of China (2014CB542102); National Key
Research and Development Program of China (2016YFC1302303); National Human Genetic Resources
Sharing Service Platform (2005DKA21300); Science Fund for Creative Research Groups, NSFC, China
(81521091); State key infection disease project of China (2017ZX10203208); National Natural Science
Foundation of China (81502375, 81472691, 81672345).

Conflicts of interest
All authors declared that there are no conflicts of interest.