title: Efficacy of interferon for chronic hepatitis B in patients with nucleoside and nucleotide combination therapy failure.
abstract: OBJECTIVE
  In China, inappropriate therapies with nucleos(t)ide analogues (NA) have induced hepatitis B virus resistance, combination therapy with nucleoside and nucleotide (ComTNsNt) failure, or multi-drug resistant mutations. However, the efficacy of combination therapy with entecavir plus tenofovir for ComTNsNt failure is limited. In the current study, the regimens of interferon-α (IFN-α) therapy, switching from NAs to IFN-α, and subsequent re-treatment with IFN-α were applied to treat ComTNsNt failure. We further evaluated the efficacy of this therapy.
  
  
  METHODS
  Eleven patients with ComTNsNt failure were enrolled in this study. Nine subjects (9/11) received IFN-α switching therapy. Combination therapy with IFN-α and ComTNsNt was administered in the first 4 weeks. Then, ComTNsNt was discontinued at the end of Week 4, and IFN-α monotherapy was continued for 6 months. Two (2/11) patients discontinued ComTNsNt without receiving IFN-α treatment. All 11 patients received the first re-treatment of IFN-α when they experienced hepatitis relapses after the withdrawal of IFN-α or ComTNsNt. Six (6/11) patients received a second re-treatment of IFN-α. Follow up was conducted after IFN-α therapy in all 11 patients.
  
  
  RESULTS
  Two patients (2/9) receiving IFN-α switching therapy experienced alanine aminotransferase (ALT) flare. In contrast, the two patients without IFN-α switching therapy experienced ALT flare. Multiple re-treatments with IFN-α resulted in a sustained response.
  
  
  CONCLUSIONS
  Interferon-α switching therapy and IFN-α re-treatment might be applied for treatment of ComTNsNt failure. IFN-α switching therapy resulted in safe ComTNsNt cessation, and IFN-α re-treatment induced a sustained response of IFN-α in all patients. This IFN-α treatment is an optional treatment for ComTNsNt failure.
authors.affiliation: Department of Infectious Disease, Nanjing Zhong-Da Hospital, Southeast University School of Medicine, Nanjing, China.
authors.forename: Guo Qing
authors.initials: GQ
authors.lastname: Yin
authors.affiliation: The Affiliated Qingyuan Hospital, Jinan University Medical School, Qingyuan, Guangdong, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Zhong
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D000068698:Tenofovir / Q000008:administration & dosage; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; C413685:entecavir; D006147:Guanine; D000068698:Tenofovir
keywords: HBV resistant mutation; IFN-α re-treatment; IFN-α switching therapy; multi-drug resistance; nucleoside and nucleotide combination therapy