Review article : The potential of interferon and nucleos(t)ide analogue combination therapy in chronic hepatitis B infection

Background: A short-term course of pegylated-interferon (Peg-IFN), or a long-term treatment with a third generation nucleot(s)ide analogue (NUC), of chronic hepatitis B (CHB) infection achieves viral suppression and may prevent disease progression. Owing to different mechanisms of action of the two regimens, a Peg-IFN and NUC combination treatment may be an attractive approach to enhance the off-treatment rates of virological and serological response. Aim: To review the literature on combinations of Peg-IFN plus NUC, including the simultaneous initiation of Peg-IFN and NUC in naïve patients; an 'add-on' combination, where Peg-IFN is started at variable times after the beginning of NUC; or a 'switch-to' strategy usually from NUC to Peg-IFN. Methods: We performed a PubMed literature search using the following terms individually or in combination: NUC, hepatitis B virus, chronic hepatitis, interferon, pegylated-interferon, nucleos(t)ide analogues, entecavir, tenofovir. English-language articles published up to December 2015, as well as conference proceedings from international meetings were reviewed. References from selected papers were reviewed and used if relevant. Results: While combination and NUC pre-treatment failed to increase HBsAg clearance rates, more promising results were achieved in patients under long-term effective NUC therapy. Conclusion: While Peg-IFN and nucleos(t)ide analogue combination therapy should not be recommended currently, the addition of or the switch to Peg-IFN in nucleos(t)ide analogue-treated patients with chronic hepatitis B infection may be useful option.