Beneficial Effects of Bushen Formula Combined with Enticavir on Chronic Hepatitis B Patients with Suboptimal Response to Enticavir by Regulating B-Cell Differentiation

Abstract

Background/Aims: To investigate the clinical effects of the combination therapy with Bushen Formula (BSF) plus enticavir (ETV) on chronic hepatitis B (CHB) patients with suboptimal response to ETV and explore the regulatory mechanisms of BSF on B cells-mediated humoral immunity. Methods: Sixty-four HBeAg-positive CHB patients with suboptimal response to ETV were enrolled, and were randomly assigned into control group (C-Group, placebo combined with ETV for 12 months) or treatment group (T-Group, BSF combined with ETV for 12 months). Serum samples from 57 treatment-naïve CHB patients and 15 healthy controls were collected. Serum HBV DNA levels were evaluated by real-time PCR. Characteristics of peripheral blood B-cell subtypes were analyzed by flow cytometry. Serum HBV markers and B cell-activating factor (BAFF) levels were detected by ELISA. Chinese medicine symptom complex score was evaluated and recorded. Results: After treatment, the rates of patients with a reduction of HBsAg > 0.5 log₁₀ IU/ml or 1.0 log₁₀ IU/ml and the rates of HBeAg clearance in T-Group were all higher than those in C-group, with no significant intergroup difference. Only in T-Group, Chinese medicine symptom complex score and the frequency of total B cells were significantly decreased, and the frequencies of Bm1, CD24⁺CD27^-switched B cells and plasma cells were markedly increased after treatment compared with those before treatment. Compared with healthy controls, serum BAFF levels in treatment-naïve CHB patients were increased, and there was a significant positive correlation between serum BAFF and HBsAg levels. However, serum BAFF levels did not differ after treatment in T-Group and C-Group. Conclusions: The combination therapy with BSF plus ETV promotes the reduction of HBsAg level and the clearance of HBeAg in CHB patients with partial response to ETV through regulating the differentiation of B-cell subsets.

Comparative serum microRNA array analysis of the spleen‐stomach dampness‐heat syndrome in different diseases: Chronic hepatitis B and chronic gastritis

“…Especially with long-term clinical application, TCM has been widely accepted as a safe and effective treatment for CHB and CG in China (Li et al, 2020;Li, Li, & Tan, 2021;Wu et al, 2020). Recent studies have shown that TCM can enhance the body's immunity to combat pathogenic microorganisms and favor the alleviation of clinical symptoms, as well as improve patients' quality of life (Li et al, 2018;Wu et al, 2020).…”

YinQiSanHuang Jiedu decoction for the treatment of hepatitis B-related compensated liver cirrhosis: study protocol for a multicentre randomised controlled trial.

“…another clinical research shows that combination therapy of traditional chinese medicine plus ETV for 48 weeks resulted in a higher rate of necro in ammatory improvement and brosis regression than ETV alone in CHB patients with serious liver brosis/cirrhosis. [14][15] The above researches have proven that TCM plays an important role in the prevention and treatment of liver brosis, however, there is still lacking of large-sample, multi-center randomized controlled studies to provide reliable and high-level evidencebased medical evidence for the prevention and treatment of liver brosis by TCM.…”

YinQiSanHuang Jiedu decoction for the treatment of hepatitis B-related compensated liver cirrhosis: study protocol for a multi-center randomized controlled trial

“…Alisma Shugan Decoction (ASD), a kind of traditional Chinese medicine compound, ameliorates hepatotoxicity and associated liver dysfunction by inhibiting oxidative stress and p65/Nrf2/JunD signaling dysregulation in vivo [ 13 ]. Clinical study has reported that the integrative medicine therapy (ETV plus TCM) can promote the reduction of HBsAg level and the clearance of HBeAg in CHB patients with partial response to ETV through regulating the differentiation of B-cell subsets; another clinical research shows that combination therapy of traditional Chinese medicine plus ETV for 48 weeks resulted in a higher rate of necroinflammatory improvement and fibrosis regression than ETV alone in CHB patients with serious liver fibrosis/cirrhosis [ 14 , 15 ]. The above researches have proven that TCM plays an important role in the prevention and treatment of liver fibrosis; however, there is still lacking of large-sample, multi-center randomized controlled studies to provide reliable and high-level evidence-based medical evidence for the prevention and treatment of liver fibrosis by TCM.…”