title: Review article: the potential of interferon and nucleos(t)ide analogue combination therapy in chronic hepatitis B infection.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Hepatology Division, Ospedale San Giuseppe, Università degli Studi di Milano, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Viganò
authors.affiliation: Division of Gastroenterology and Hepatology, "A.M. e A. Migliavacca" Center for the Study of Liver Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Invernizzi
authors.affiliation: Division of Gastroenterology and Hepatology, "A.M. e A. Migliavacca" Center for the Study of Liver Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Grossi
authors.affiliation: Division of Gastroenterology and Hepatology, "A.M. e A. Migliavacca" Center for the Study of Liver Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Lampertico
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D006515:Hepatitis B virus / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D007372:Interferons