Efficacy of interferon for chronic hepatitis B in patients with nucleoside and nucleotide combination therapy failure

Background and Aim: 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-alpha (IFN-alpha) therapy, switching from NAs to IFN-alpha, and subsequent re-treatment with IFN-alpha 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-alpha switching therapy. Combination therapy with IFN-alpha and ComTNsNt was administered in the first 4 weeks. Then, ComTNsNt was discontinued at the end of Week 4, and IFN-alpha monotherapy was continued for 6months. Two (2/11) patients discontinued ComTNsNt without receiving IFN-alpha treatment. All 11 patients received the first re-treatment of IFN-alpha when they experienced hepatitis relapses after the withdrawal of IFN-alpha or ComTNsNt. Six (6/11) patients received a second re-treatment of IFN-alpha. Follow up was conducted after IFN-alpha therapy in all 11 patients. Results: Two patients (2/9) receiving IFN-alpha switching therapy experienced alanine aminotransferase (ALT) flare. In contrast, the two patients without IFN-alpha switching therapy experienced ALT flare. Multiple re-treatments with IFN-alpha resulted in a sustained response. Conclusions: Interferon-alpha switching therapy and IFN-alpha re-treatment might be applied for treatment of ComTNsNt failure. IFN-alpha switching therapy resulted in safe ComTNsNt cessation, and IFN-alpha re-treatment induced a sustained response of IFN-alpha in all patients. This IFN-alpha treatment is an optional treatment for ComTNsNt failure.