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Zheng et al. Hepatoma Res 2018;4:17 I http://dx.doi.org/10.20517/2394-5079.2018.08 Page 5 of 8

Thus, it is necessary to clarify the details of the host-virus relationship during HBV infection to facilitate the
development of efficient therapeutic strategies for HBV infection.

To prevent HCC, targeting HBV-induced ER stress may provide novel strategies in high-risk CHB.
Antioxidants may be such ideal agents, because they reduce ER stress, thereby improving protein folding .
[91]
Natural products, including silymarin and resveratrol, have been used in HCC. The two drugs target ER
stress-associated signal pathways . The pre-S2 mutant initiated an mTOR-dependent glycolytic pathway to
[7]
activate the solute carrier family 2 member 1 (SLC2A1), contributing to aberrant glucose uptake and lactate
production in advanced stages of pre-S2 mutant transgenic tumorigenesis; the mTOR signaling cascade
in pre-S2 mutant-mediated hepatocarcinogenesis was inhibited by the combined treatment of resveratrol
and silymarin . However, these findings require further validation. Glycyrrhizin acid (GA) has also
[79]
been reported to suppress ER stress in acute liver injury via several functions, including effective hepato-
protection and the reduction of elevated transaminases . Long-term treatment with glycyrrhizin prevented
[92]
HCC development in chronic hepatitis C infection . Together, these strategies for prevention and treatment
[93]
of HBV-related HCC should be further investigated.

DECLARATIONS
Authors’ contributions
Drafted the manuscript: Zheng Y
Revised the manuscript: Qian YY
Revised and approved the final version: Fan H

Financial support and sponsorship
This work was funded by the grants from National Natural Science Foundation of China (81672414, 81472548,
and 81702906).

Conflicts of interest
There are no conflicts of interest.

Patient consent
Not applicable.

Ethics approval
Not applicable.

Copyright
© The Author(s) 2018.

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