Treatment of hepatitis B: Is there still a role for interferon?

The treatment of chronic hepatitis B (CHB) patients is based on monotherapy with pegylated-interferon (Peg-IFN) or with one of the three most potent nucleot(s)ide analogues (NUCs) with the best resistance profiles, i.e. entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). Long-term NUCs treatment can achieve virological suppression in almost all patients. However, this requires lifelong therapy, is costly and the rate of hepatitis B surface antigen (HBsAg) seroclearance is low. A one-year course of Peg-IFN has the advantage of providing immune-mediated control of the hepatitis B virus (HBV) infection, the possibility of achieving a sustained off-treatment response in nearly 30% of the patients and ultimately, HBsAg loss in approximately 30%-50% of the latter patients during long-term off treatment follow-up. However, the major limitations to the extensive use of this treatment are the need for parenteral therapy and clinical and laboratory monitoring, the side-effects profile and contraindications in certain patients and the limited effectiveness in a large proportion of patients. Nevertheless, the cost-effectiveness of Peg-IFN can be significantly increased by careful patient selection based upon baseline alanine aminotransferase (ALT), HBV DNA levels, viral genotype, host genetic variants and especially by applying early on-treatment stopping rules based upon HBsAg kinetics. Recently, because of the different mechanisms of action of Peg-IFN and NUCs, the strategy of "adding-on" or "switching to" Peg-IFN in patients being treated with NUCs to accelerate the decline in HBsAg and enhance HBsAg seroclearance rates, has provided interesting results.