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

Abstract 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‐ 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.