Interferon and Hepatitis B: Current and Future Perspectives

Abstract

Chronic hepatitis B virus (HBV) infection remains a major health burden worldwide for which there is still no effective curative treatment. Interferon (IFN) consists of a group of cytokines with antiviral activity and immunoregulatory and antitumor effects, that play crucial roles in both innate and adaptive immune responses. IFN-α and its pegylated form have been used for over thirty years to treat chronic hepatitis B (CHB) with advantages of finite treatment duration and sustained virologic response, however, the efficacy is limited and side effects are common. Here, we summarize the status and unique advantages of IFN therapy against CHB, review the mechanisms of IFN-α action and factors affecting IFN response, and discuss the possible improvement of IFN-based therapy and the rationale of combinations with other antiviral agents in seeking an HBV cure.

Sequential Combination of a Strong Interferon Inducer Viral Vector With Low Doses of Nivolumab Plus Ipilimumab Could Provide Functional Cure in Chronic Hepatitis B Virus infections: Technical Report Proposing a New Modality

“…In this context, it is important to recall that IFN-β has the highest binding affinities for the IFN receptors, however, it is more toxic in patients, probably because of its high antiproliferative activity. In addition to type I IFN, type III IFNs, consisting of four IFN-λ subtypes, have been considered as an alternative in the treatment of CHB [1]. Therefore, the particular cytokine induction profile of IBDV maximizes antiviral action with minimal side effects in CHB patients, opening up the therapeutic window.…”

“…More than 250 million individuals worldwide are chronically infected by the hepatitis B virus (HBV), which causes over 780 thousand deaths every year [1]. The standard of care consists of two main antiviral therapies: nucleos(t)ide analogs (NAs) and pegylated interferon alpha (PEG-IFN).…”

“…Antiviral immune modulation IFN therapy has unique mechanistic advantages over NAs because it disrupts immune tolerant states in chronic hepatitis B (CHB) patients who are unable to mount an immune response to clear the infection. However, the safety and efficacy of PEG-IFN are still not satisfactory [1].…”

“…Despite a variety of antiviral agents in clinical development targeting various steps of the HBV life cycle (e.g., viral RNA interference molecules, capsid assembly blockers, immune checkpoint inhibitors (ICIs), hepatitis B surface antigen (HbsAg), cccDNA generation blocking molecules, and innate immune system modulators), none of them is expected to effectively cure CHB in the foreseeable future [1,2].…”

Regulation of Pattern-Recognition Receptor Signaling by HBX During Hepatitis B Virus Infection

“…Although the hepatitis B virus (HBV), a small DNA virus, has been known for more than 50 years, chronic infection caused by this virus remains a global cause of hepatitis, cirrhosis, and liver cancer, especially hepatocellular carcinoma (HCC) ( 1 – 3 ). It has been widely demonstrated that after recognition by pattern recognition receptors (PRRs), the virus can be restrained by the innate immune system ( 4 – 7 ). To date, four types of PRRs, including toll-like receptors (TLRs), cytosolic DNA sensors, retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), and NOD-like receptors (NLRs), have been discovered ( 8 – 10 ).…”