scholarly journals Suppression of Interferon-α Treatment Response by Host Negative Factors in Hepatitis B Virus Infection

2021 ◽  
Vol 8 ◽  
Author(s):  
Jiayi Wang ◽  
Lingyao Du ◽  
Hong Tang

Chronic hepatitis B virus (CHB) infection remains a major global public health issue for which there is still lacking effective curative treatment. Interferon-α (IFN-α) and its pegylated form have been approved as an anti-HBV drug with the advantage of antiviral activity and host immunity against HBV infection enhancement, however, IFN-α treatment failure in CHB patients is a challenging obstacle with 70% of CHB patients respond poorly to exogenous IFN-α treatment. The IFN-α treatment response is negatively regulated by both viral and host factors, and the role of viral factors has been extensively illustrated, while much less attention has been paid to host negative factors. Here, we summarized evidence of host negative regulators and parameters involved in IFN-α therapy failure, review the mechanisms responsible for these effects, and discuss the possible improvement of IFN-based therapy and the rationale of combining the inhibitors of negative regulators in achieving an HBV cure.

1994 ◽  
Vol 39 (9) ◽  
pp. 2014-2021 ◽  
Author(s):  
Jane W. S. Fang ◽  
P. C. WU ◽  
C. L. Lai ◽  
C. K. LO ◽  
Anthony Meager ◽  
...  

Hepatology ◽  
1991 ◽  
Vol 13 (2) ◽  
pp. 332-338 ◽  
Author(s):  
Johnson Y. N. Lau ◽  
Nick Sheron ◽  
Alan G. Morris ◽  
Adrian B. Bomford ◽  
Graeme J. M. Alexander ◽  
...  

Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Gang Wang ◽  
Jun Guan ◽  
Nazif U. Khan ◽  
Guojun Li ◽  
Junwei Shao ◽  
...  

AbstractInterferon-alpha (IFN-α) and nucleot(s)ide analogs (NAs) are first-line drugs for the treatment of chronic hepatitis B virus (HBV) infections. Generally, NAs target the reverse transcription of HBV pregenomic RNA, but they cannot eliminate covalently-closed-circular DNA (cccDNA). Although effective treatment with NAs can dramatically decrease HBV proteins and DNA loads, and even promote serological conversion, cccDNA persists in the nucleus of hepatocytes due to the lack of effective anti-cccDNA drugs. Of the medications currently available, only IFN-α can potentially target cccDNA. However, the clinical effects of eradicating cccDNA using IFN-α in the hepatocytes of patients with HBV are not proficient as well as expected and are not well understood. Herein, we review the anti-HBV mechanisms of IFN-α involving cccDNA modification as the most promising approaches to cure HBV infection. We expect to find indications of promising areas of research that require further study to eliminate cccDNA of HBV in patients.


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