Outcome of Chinese patients with hepatitis B at 96 weeks after functional cure with IFN versus combination regimens

Abstract

Background & Aims Nucleotides with add‐on interferon treatment (NUC‐IFN) provide significantly higher rates of hepatitis B surface antigen (HBsAg) loss in patients with chronic hepatitis B (CHB). This study aimed to investigate the sustainability of HBsAg loss and the prevention of clinical relapse. Methods Patients with CHB who achieved HBsAg loss and HBV DNA levels <20 IU/ml after IFN or NUC‐IFN therapy were enrolled and followed up for 96 weeks. The primary outcome was HBsAg negativity without viremia at week 96. Secondary outcomes included virological or clinical relapse and predictors of relapse. Results 420 patients were included in intention‐to‐treat analysis with 290 and 130 in the IFN and NUC‐IFN groups respectively. At week 96, the intention‐to‐treat analysis revealed similar outcomes between groups, including HBsAg seroreversion (24.83% vs. 23.08%, P = .70), viremia (16.90% vs 13.08%, P = .32) and clinical relapse (11.38% vs 10.00%, P = .68); the per‐protocol analyses also showed HBsAg seroreversion, viremia and clinical relapse in IFN group (15.50%, 6.59% and 0.39%) did not differ from those in NUC‐IFN group (15.25%, 4.24% and 0.85%, P > .05). These outcomes were similar between patients who received entecavir and those who received telbivudine/lamivudine/adefovir before the combination therapy. In NUC‐IFN‐treated patients, fibrosis regression was observed at week 96. Baseline HBsAb negativity was independent predictors of HBsAg sero‐reversion and recurrence of viremia in IFN treated group. Conclusion NUC‐IFN and IFN therapies are equally effective in achieving sustained functional cure and fibrosis regression. (ClinicalTrials.gov, Number NCT02336399).

Efficacy and safety of peginterferon alpha monotherapy in Chinese inactive chronic hepatitis B virus carriers

“…However, multiple recent studies have definitively demonstrated that HBsAg clearance induced by peg-IFNα was durable during long-term follow-up and the incidence of HCC was extremely low (<1.5%) in HBV clinically cured patients. [27][28][29][30][31] Furthermore, even some patients were not clinically cured, a full course of peg-IFNα treatment also induced favourable outcomes during long-term follow-up, including HBsAg clearance and no disease progression. 32 The long-term effectiveness data collection of this study is ongoing, and the subsequent results will also be reported in the future.…”

B Cell-mediated Humoral Immunity in Chronic Hepatitis B Infection

“…The functional cure of CHB has been considered as a feasible clinical treatment goal, 7,8 which is correlated with improved clinical outcomes. 9 Nevertheless, only a small proportion of patients reach this milestone. 10,11 The complex interaction between HBV and the host immune system drives the process of chronic HBV infection, in which the anti-HBV adaptive immune system processes facilitate the clearance of HBV.…”

“…The functional cure of CHB has been considered as a feasible clinical treatment goal, 7 , 8 which is correlated with improved clinical outcomes. 9 Nevertheless, only a small proportion of patients reach this milestone. 10 , 11 …”

No additive effects of peginterferon on the short-term improvement of liver histology by entecavir monotherapy in chronic hepatitis B patients

“…Chen et al revealed that entecavir and pegylated interferon-alpha-2a add-on therapy has no impacts on the shortterm improvement of liver histology of patients with chronic hepatitis B in China, where the major HBV genotype was genotype C [7]. Combination therapy may contribute to long-term improvement of liver histology compared with NUC monotherapy [10]. Further investigations regarding the mechanism of interferon signaling pathways and the effects in the combination of pegylated interferon and NUCs on HBsAg loss, suppression of hepatocarcinogenesis, and the longer-term observation of liver histology or elastography should be conducted.…”