Journal article
Mechanism of interferon alpha therapy for chronic hepatitis B and potential approaches to improve its therapeutic efficacy
Antiviral research, v 221, pp 105782-105782
17 Dec 2023
PMID: 38110058
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Hepatitis B virus (HBV) chronically infects 296 million people worldwide and causes more than 820,000 deaths annually due to cirrhosis and hepatocellular carcinoma. Current standard-of-care medications for chronic hepatitis B (CHB) include nucleos(t)ide analogue (NA) viral DNA polymerase inhibitors and pegylated interferon alpha (PEG-IFN-α). NAs can efficiently suppress viral replication and improve liver pathology, but not eliminate or inactivate HBV covalently closed circular DNA (cccDNA). CCC DNA is the most stable HBV replication intermediate that exists as a minichromosome in the nucleus of infected hepatocyte to transcribe viral RNA and support viral protein translation and genome replication. Consequentially, a finite duration of NA therapy rarely achieves a sustained off-treatment suppression of viral replication and life-long NA treatment is most likely required. On the contrary, PEG-IFN-α has the benefit of finite treatment duration and achieves HBsAg seroclearance, the indication of durable immune control of HBV replication and functional cure of CHB, in approximately 5% of treated patients. However, the low antiviral efficacy and poor tolerability limit its use. Understanding how IFN-α suppresses HBV replication and regulates antiviral immune responses will help rational optimization of IFN therapy and development of novel immune modulators to improve the rate of functional cure. This review article highlights mechanistic insight on IFN control of HBV infection and recent progress in development of novel IFN regimens, small molecule IFN mimetics and combination therapy of PEG-IFN-α with new direct-acting antivirals and therapeutic vaccines to facilitate the functional cure of CHB.
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Details
- Title
- Mechanism of interferon alpha therapy for chronic hepatitis B and potential approaches to improve its therapeutic efficacy
- Creators
- Qiong Zhao - Baruch S. Blumberg InstituteHui Liu - Baruch S. Blumberg InstituteLiudi Tang - Baruch S. Blumberg InstituteFuxuan Wang - Baruch S. Blumberg InstituteGideon Tolufashe - Baruch S. Blumberg InstituteJinhong Chang - Baruch S. Blumberg InstituteJu-Tao Guo - Baruch S. Blumberg Institute
- Publication Details
- Antiviral research, v 221, pp 105782-105782
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:001143396800001
- Scopus ID
- 2-s2.0-85180593412
- Other Identifier
- 991021811736804721
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InCites Highlights
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- Web of Science research areas
- Pharmacology & Pharmacy
- Virology