The expression of interleukin-1β in patients with chronic hepatitis B treated with pegylated-interferon-alpha combined with tenofovir disoproxil fumarate and monotherapy

Abstract

BackgroundAnti-hepatitis B virus (HBV) treatment uses tenofovir disoproxil fumarate (TDF) along with Pegylated-interferon-alpha (Peg-IFN-α), which is more effective than TDF/Peg-IFN-α monotherapy. We have previously shown that interleukin-1beta (IL-1β) is related to the effectiveness of IFN-α treatment in chronic hepatitis B (CHB) patients. The aim was to investigate the expression of IL-1β in CHB patients treated with Peg-IFN-α combination with TDF and TDF/Peg-IFN-α monotherapy.MethodsHuh7 cells infected with HBV were stimulated by Peg-IFN-α and/or Tenofovir (TFV) for 24h. A single-center cohort study of prospective recruitment of CHB patients: untreated CHB (Group A), TDF combined with Peg-IFN-α therapy (Group B), Peg-IFN-α monotherapy (Group C), TDF monotherapy (Group D). Normal donors served as controls. The clinical datas and blood of patients were collected at 0, 12, and 24 weeks. According to the early response criteria, Group B and C were divided into two subgroups: the early response group (ERG) and the non-early response group (NERG). Stimulation of HBV-infected hepatoma cells with IL-1β to validate the antiviral activity of IL-1β. To test the blood sample, cell culture supernatant, and cell lysates and to assess the expression of IL-1β and HBV replication levels in various treatment protocols, Enzyme-Linked Immunosorbent Assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used. SPSS 26.0 and GraphPad Prism 8.0.2 software were used for statistical analysis. P values < 0.05 was considered to be statistically significant.ResultsIn vitro experiments, Peg-IFN-α plus TFV treatment group expressed higher IL-1β and inhibited HBV more effectively than monotherapy. Finally, 162 cases were enrolled for observation (Group A (n = 45), Group B (n = 46), Group C (n = 39), and Group D (n = 32)), and normal donors (n = 20) were enrolled for control. The early virological response rates of Group B, C, and D were 58.7%, 51.3%, and 31.2%. At 24 weeks, IL-1β in Group B(P = 0.007) and C(P = 0.034) showed higher than at 0 week. In Group B, the IL-1β showed an upward trend at 12w and 24w in the ERG. IL-1β significantly reduced HBV replication levels in hepatoma cells.ConclusionThe increased expression of IL-1β may enhance the efficacy of TDF combined with Peg-IFN-α therapy in achieving an early response for CHB patients.