HBeAg-positive chronic hepatitis B: why do I treat my patients with pegylated interferon?

Although chronic hepatitis B (CHB) is a global health threat, it is now a preventable and treatable disease. Seven agents have been approved for the treatment of CHB. Although many patients prefer potent long-term nucleos(t)ide analogues (NAs) as the first-line therapy because they are convenient to use and well-tolerated, a finite duration of pegylated interferon (PEG-IFN) is still an attractive strategy because it provides higher rates of off-therapy host immune control over hepatitis B virus (HBV) compared with NAs. In addition, the rates of HBeAg/HBsAg loss or seroconversion increase over time in patients who respond to PEG-IFN therapy. Nevertheless, these benefits are limited to 30% of all patients, and significant adverse effects are still a concern. Therefore, patients who can benefit most from PEG-IFN therapy should be more carefully selected according to baseline host and viral predictors, such as age, ALT level, viral load, HBV genotype and HBV mutants. In addition, on-treatment predictors including HBV DNA, HBeAg and HBsAg kinetics, can help decide who should continue or discontinue PEG-IFN and shift to NA. Understanding these factors can help determine personalized PEG-IFN therapy for CHB patients. In the near future, the treatment paradigm of CHB should be tailored on the basis of viral (HBV DNA level, HBV genotype and HBV mutants) and host (age, gender, ALT level and host genetic polymorphisms) factors, disease status (stage of fibrosis and comorbidities) and the selection of antiviral agents (immunomodulatory effect, antiviral potency, adverse effects and rate of drug resistance).