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

2018 ◽  
Vol 48 (2) ◽  
pp. 633-643 ◽  
Author(s):  
Man Li ◽  
Zhen-Hua Zhou ◽  
Ting Bao ◽  
Xin Zhang ◽  
Xiao-Jun Zhu ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
B Cells ◽  
Chinese Medicine ◽  
Hepatitis B ◽  
Combination Therapy ◽  
B Cell ◽  
Chronic Hepatitis B ◽  
Healthy Controls ◽  
Treatment Naïve ◽  
Symptom Complex

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.

scholarly journals Immunomodulatory Effects of Combination Therapy with Bushen Formula plus Entecavir for Chronic Hepatitis B Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Long-Shan Ji ◽  
Qiu-Tian Gao ◽  
Ruo-Wen Guo ◽  
Xin Zhang ◽  
Zhen-Hua Zhou ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Chinese Medicine ◽  
Combination Therapy ◽  
Virological Response ◽  
Healthy Controls ◽  
Expression Levels ◽  
Treg Frequency ◽  
Treatment Naïve ◽  
Symptom Complex ◽  
Partial Virological Response

Aim. To compare the clinical efficacy of the combination therapy with Bushen formula (BSF) plus entecavir (ETV) in naïve chronic hepatitis B (CHB) patients and that in CHB patients with partial virological response to ETV and explore the relevant immunoregulatory mechanism. Materials and Methods. Two hundred and twenty CHB patients were enrolled in the historical prospective cohort study. Patients were categorized into a treatment group (T-Group: combination therapy with BSF plus ETV) and a control group (C-Group: ETV). Patients in T-Group and C-Group were grouped into T1/C1 (treatment-naïve patients) and T2/C2 (patients with partial virological response to ETV). Biochemical assessment, viral load quantitation, and HBV markers were tested. Chinese medicine symptom complex score was evaluated and recorded as well. In addition, peripheral blood mononuclear cells were separated from blood samples in 56 patients and 11 healthy donors. The frequencies of Th1, Treg, and dendritic cells (DCs) and expression levels of PD-1/PD-L1 were examined by flow cytometry. Results. In treatment-naïve CHB patients, complete viral suppression rates in HBeAg(−) patients were higher than those in HBeAg(+) patients in both T and C groups. In patients with partial virological response to ETV, the rate of HBsAg decline ≥ 20% in HBeAg(+) patients of T2-Group was higher than that in HBeAg(+) patients of C2-Group. A significant reduction of Chinese medicine symptom complex score was only observed in T-Group. The study of mechanism showed that, compared with healthy controls, Th1 and DC frequencies were decreased in all CHB patients, while Treg frequency was increased only in treatment-naïve patients. In addition, compared with healthy controls, PD-1 expression levels on Th1 and Treg were increased in all patients and PD-L1 expression levels on DCs were increased only in treatment-naïve patients. In treatment-naïve patients, the combination therapy with BSF plus ETV increased Th1 and DC frequencies and decreased Treg frequency, which was correlated with HBsAg decline. In addition, in patients with partial virological response to ETV, the combination therapy downregulated PD-L1 levels on DCs and the frequency of Treg, which was related with HBsAg decline. Conclusions. In patients with partial virological response to ETV, HBeAg(+) patients tend to achieve ideal effects after the combination therapy with BSF plus ETV, which may correlate with the decrease of Treg frequency and the downregulation of PD-L1 levels on DCs.

Transcriptomic profiling of intrahepatic B cells suggests a B-cell impairment in the immune active phase of chronic hepatitis B

2018 ◽  
Vol 68 ◽  
pp. S792 ◽  
Author(s):  
S.V. Hees ◽  
J. Hou ◽  
A. Grooshuismink ◽  
K. Kreefft ◽  
S. Bourgeois ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
B Cells ◽  
Hepatitis B ◽  
B Cell ◽  
Chronic Hepatitis B ◽  
Active Phase ◽  
Transcriptomic Profiling

The partial virological response to Tenofovir monotherapy in naïve patients with chronic hepatitis B

2020 ◽  
pp. 1-12
Author(s):  
Habip Gedik ◽  
Muge Sonmezisik
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Partial Response ◽  
Combination Therapy ◽  
Chronic Hepatitis B ◽  
Antiviral Drug ◽  
Sustained Viral Response ◽  
Treatment Naïve ◽  
Tenofovir Alafenamide ◽  
Partial Virological Response

Abstract We report two treatment-naïve cases, a 26-year-old female patient and a 59-year-old male patient who were followed up for chronic hepatitis B (CHB) at the Department of Infectious Diseases and Clinical Microbiology. A partial response subsequent to 12 months of Tenofovir Disoproksil (TDF) monotherapy presumably due to an antiviral-drug resistance was noted. A sustained viral response with TDF (245 mg) or Tenofovir Alafenamide (TAF, 25 mg) + Entecavir (ETV, 1 mg) combination therapy was observed after failure with TDF monotherapy. A combination therapy with TDF (245 mg) or TAF (25 mg) +ETV (1 mg) is efficacious in naïve patients with a partial response to TDF monotherapy. Keywords: Chronic hepatitis B, Tenofovir, partial response, Entecavir, combination therapy

scholarly journals Classification of Traditional Chinese Medicine Syndromes in Patients with Chronic Hepatitis B by SELDI-Based ProteinChip Analysis

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Ya-Nan Song ◽  
Hui Zhang ◽  
Yan Guan ◽  
Jing-Hua Peng ◽  
Yi-Yu Lu ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Partial Least Square ◽  
Healthy Controls ◽  
Protein Profiles ◽  
Tcm Syndrome

Traditional Chinese medicine (TCM) syndrome, also called ZHENG, is the basis concept of TCM theory. It plays an important role in TCM practice. There are excess and deficiency syndromes in TCM syndrome. They are the common syndromes in chronic hepatitis B (CHB) patients. Here we aim to explore serum protein profiles and potential biomarkers for classification of TCM syndromes in CHB patients. 24 healthy controls and two cohorts of CHB patients of excess syndrome (n=25) or deficiency syndrome (n=19) were involved in this study. Protein profiles were obtained by surface-enhanced laser desorption ionization time-flight mass spectrometry (SELDI-TOF/MS) and multiple analyses were performed. Based on SELDI ProteinChip data, healthy controls and CHB patients or excess and deficiency syndromes in CHB patients were obviously differentiated by orthogonal partial least square (OPLS) analysis. Two significant serum proteins (m/z 4187 and m/z 5032) for classifying excess and deficiency syndromes were found. Moreover, the area under the receiver operating characteristic (ROC) curve was 0.887 for classifying excess and nonexcess syndrome, and 0.700 for classifying deficiency and nondeficiency syndrome, respectively. Therefore, the present study provided the possibility of TCM syndrome classification in CHB patients using a universally acceptable scientific approach.

scholarly journals Skewed CD39/CD73/adenosine pathway contributes to B-cell hyperactivation and disease progression in patients with chronic hepatitis B

2020 ◽  
Author(s):  
Shuang-Nan Zhou ◽  
Ning Zhang ◽  
Hong-Hong Liu ◽  
Peng Xia ◽  
Chao Zhang ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
B Cells ◽  
Hepatitis B ◽  
B Cell ◽  
Chronic Hepatitis B ◽  
Hbeag Seroconversion ◽  
Liver Inflammation ◽  
Activation Markers ◽  
Chronic Hepatitis B Virus ◽  
Cd73 Expression

Abstract Background The mechanisms underlying B-cell hyperactivation in patients with chronic hepatitis B virus (HBV) infection remain largely undefined. The present study assessed the clinical characteristics of the CD39/CD73/adenosine pathway in patients with chronic hepatitis B (CHB). Methods We examined CD39 and CD73 expression and adenosine production by B-cells from 202 HBV-infected patients. B-cell-activation phenotypes were assessed by flow cytometry after CpG+CD40 ligand stimulation with or without blockade and activation of the adenosine pathway. Results CD39 and CD73 expression on circulating B-cells was decreased in CHB patients with high HBV DNA, HBeAg positivity, high HBsAg levels, and active liver inflammation, and was hierarchically restored in complete responders according to HBeAg seroconversion or HBsAg reduction. However, CD39 and CD73 expression on activated memory and tissue-like memory B-cell subsets in complete responders was not increased despite effective antiviral treatments. Furthermore, CD39 and CD73 expression on intra-hepatic B-cells was decreased in inflammatory livers. In vitro, B-cells from CHB patients showed a markedly reduced capacity to generate CD39/CD73-dependent extracellular adenosine and expressed increased levels of activation markers after adenosine-production blockade. Contrastingly, metformin significantly reduced activation-marker expression via regulating AMP-activated protein kinase. Conclusions The skewed CD39 and CD73 expression on B-cells was associated with a high viral burden, liver inflammation, and antiviral efficacy in CHB patients, and the skewed CD39/CD73/adenosine pathway contributed to B-cell hyperactivation. Regulation of the CD39/CD73/adenosine pathway using metformin may represent a therapeutic option to reverse HBV-induced immune pathogenesis.

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