Hepatitis B and D: Interferon‐Based Therapy—For Clinical Trials or Standard of Care—Back to the Future?

Interferon (IFN) has historically played a major role in chronic viral hepatitis B and D management over the last three decades. Widening utilisation of nucleoside/nucleotide analogues (NUCs) for hepatitis B viral suppression, which have a better side-effect profile, alongside the recent licensing of bulevirtide for treatment of hepatitis D, means that its clinical use has further declined. Pegylated-interferon alpha (peg-IFNα) treatment is suboptimal with poor tolerability and achieves durable clearance of hepatitis B and D in only a limited number of patients. Nevertheless, its use in hepatitis B has significantly increased the number of patients achieving hepatitis B surface antigen (HBsAg) loss compared to those on NUCs alone. Evidence has shown that peg-IFNα is also associated with overall improved long-term clinical outcomes in chronic hepatitis D, even for the many whose hepatitis D viral load rebounds after discontinuation. Clinical trials have recently focused on peg-IFNα in combination with novel antiviral therapies in the goal for finite cure in hepatitis B and D. This article focuses on recent research advances, examining if peg-IFNα treatment may still play an important role in hepatitis B and D treatment.