A Phase 2 open label study of ledipasvir/sofosbuvir for 12 weeks in subjects with hepatitis B virus infection

Retrospective data showed that when we administered ledipasvir/sofosbuvir (LDV/SOF) to patients with hepatitis B and C coinfection, there was a modest reduction in hepatitis B surface antigen (HBsAg). Therefore, we hypothesize that similar HBsAg reduction can be seen in hepatitis B virus (HBV) monoinfected subjects. Primary and secondary efficacy endpoints are the decline in HBsAg and HBV DNA at Week 12 from baseline, respectively. We conducted an open-label Phase 2 pilot study to evaluate the safety, tolerability, and antiviral activity of LDV and/or SOF for HBV. Eligible subjects were either suppressed on antivirals (Group B) or inactive chronic HBV (Group A, C, D). Group A and B received LDV/SOF. Group C and D received SOF 400 mg and LDV 90 mg, respectively. All subjects completed the study, and all related adverse events (AEs) were mild. No discontinuations due to AEs or hepatitis flare occurred. At Week 12, HBsAg decline (log₁₀ IU/ml) was similar between Group A (0.399) and B (0.400), less in Group C (0.207), and none in Group D, and there was HBV DNA decline in the inactive chronic HBV groups. LDV and SOF are safe and well tolerated when given to chronic hepatitis B subjects and have modest antiviral activity, particularly when given in combination.     

Decreased frequency of a novel T-lymphocyte subset,CD3+CD4−CD7+CD57− T cells,in hepatitis B virus-related end-stage liver disease might contribute to disease progression

CD7 and CD57 are related to the differentiation and functional stages of CD8⁺ T cells. However, the role of their combined presence in CD8⁺ T cells in patients with chronic hepatitis B virus (HBV) infection, especially those with end-stage liver disease, remains unclear. Blood samples from healthy volunteers and patients with chronic hepatitis B were analyzed via Luminex assay and ELISA to measure plasma cytokine levels. Further, recombinant IL-22 was used to stimulate peripheral blood mononuclear cells from healthy volunteers, and the frequency of CD3⁺CD4⁻CD7⁺CD57⁻ T cells and apoptosis rates were investigated via flow cytometry. Patients with end-stage liver disease, particularly those with acute to chronic liver failure, showed decreased CD3⁺CD4⁻CD7⁺CD57⁻ T cell frequency. Furthermore, the prevalence of CD3⁺CD4⁻CD7⁺CD57⁻ T cells was negatively correlated with disease severity, prognosis, and complications (ascites). We also observed that IL-22 promoted apoptosis and brought about a decrease in the number of CD3⁺CD4⁻CD7⁺CD57⁻ T cells in a dose-dependent manner. CD3⁺CD4⁻CD7⁺CD57⁻ T cells displayed a B and T lymphocyte attenuator (BTLA)^highCD25^highCD127^high immunosuppressive phenotype and showed low interferon-γ, tumor necrosis factor-α, granzyme A, and perforin expression levels. The present findings will elucidate the pathogenesis of HBV-related end-stage liver disease and aid the identification of novel drug targets.     

The third inactivated vaccine booster dramatically enhanced SARS-CoV-2 antibody responses and did not influence the profile of prothrombotic antibody

The purpose of this study is to investigate the production of both severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific antibodies and autoantibodies in serum following the third booster vaccination of the inactivated COVID-19 vaccine, and to study the effect of B cell subsets with CD27 and CD38 phenotypes in peripheral blood on antibody production. Routine blood indexes, SARS-CoV-2 antibodies, platelet factor 4 and seven antiphospholipid antibodies were detected both before and 2 months after vaccination in the medical staff of the Zhongnan Hospital of Wuhan University. Peripheral blood B cell subtypes were detected before vaccination. Following immunization, the positive rate of anti-N-S1 immunoglobulin (IgG) had increased from 24.8% to 91.3% and the average antibody concentration had increased by 11 times. The positive rate of neutralizing antibody had increased from 24.8% to 91.3%, the average antibody concentration had increased by 12 times, and the primary increased anti-S1 IgG subtype was that of IgG1. Peripheral blood CD27 + CD38+ B cells were positively correlated with antibody levels after vaccination and were a predictor of the antibody response. In addition, although some indicators showed slight absolute changes, the blood parameters and antiphospholipid antibodies of most volunteers were normal both before and after COVID-19 inactivated vaccine inoculation, and there was no statistical difference in abnormal rates either before or after inoculation. Antibodies in vivo were increased after vaccination with the inactivated vaccine, and IgG1 was the main subtype involved in response to the vaccine. Vaccination with the inactivated COVID-19 vaccine did not appear to affect thrombus-related autoantibodies.     

Risk factors for hepatocellular carcinoma at baseline and 1 year after initiation of nucleos(t)ide analog therapy for chronic hepatitis B

Nucleos(t)ide analogs (NAs) cannot completely suppress the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study aimed to identify the risk factors for HCC development in naïve CHB patients treated with current NA. Patients receiving NA (n = 905) were recruited retrospectively from the 17 hospitals of the Japanese Red Cross Liver Study Group. All treatment-naïve patients had been receiving current NA continuously for more than 1 year until the end of the follow-up. We analyzed the accuracy of predictive risk score using the area under receiver operating characteristic curve. The albumin–bilirubin (ALBI) score was significantly improved by NA therapy (−0.171 ± 0.396; p < 0.001 at Week 48). A total of 72 (8.0%) patients developed HCC over a median follow-up of 6.2 (1.03–15.7) years. An independent predictive factor of HCC development was older age, cirrhosis, lower platelet counts at baseline and ALBI score, and alpha-fetoprotein (AFP) at 1 year after NA therapy according to multivariate analysis. The accuracy was assessed using the PAGE-B, mPAGE-B, aMAP, APA-B, and REAL-B scores that included these factors. Discrimination was generally acceptable for these models. aMAP and REAL-B demonstrated high discrimination with 0.866/0.862 and 0.833/0.859 for 3- and 5-year prediction from the status of 1 year after NA therapy, respectively. Baseline age and platelet count, as well as ALBI and AFP one year after NA, were useful for stratifying carcinogenesis risk. The aMAP and REAL-B scores were validated with high accuracy in Japanese CHB patients.     

Pre-S2、抗Pre-S2和HBVDNA在乙型肝炎患者中的相关性分析

目的：探讨Pre-S2,抗Pre-S2二对半和HBV DNA对乙型肝炎患者血清的诊断意义。方法：用ELISA法和PCR法分别检测93例乙型肝炎患者和28例健康人血清中的Pre-S2,抗Pre-S2,二对半和HBV DNA水平。结果：93例乙肝患者HBsAg,HBeAg,HBcAb阳性32例,HBsAg,HBeAb,HBcAb阳性39例,HBsAg,HBcAb阳性18例,HBcAb阳性4例。Pre-S2结果阳性率66．7％（62／93）,Pre-S2抗体结果阳性率1．1％（1／93）,HBV DNA结果阳性率40．9％（38／93）,28例健康人二对半,五项全阴16例,HBsAb阳性12例,Pre-S2阳性1例,HBV DNA阳性1例,Pre-S2抗体阳性5例占HBsAb阳性47．7％（5／12）,Pre-S2和HBV DNA相比有明显差异（P＜0．01）,非HBeAg阳性组中HBV DNA阳性率约低于Pre-S2。结论：Pre-S2,抗Pre-S2,HBV DNA和二对半在乙型肝炎血清学诊断中显示,Pre-S2优于HBV DNA和二对半,Pre-S2抗体出现早于抗HBs和抗HBe,抗Pre-S2阳性检出率较低,可能同乙型肝炎疫苗中抗Pre-S2含量低有关。     

EGb761对抗海人藻酸神经毒性的作用

目的：探讨银杏叶提取物（ＥＧｂ７６１）对海人藻酸（ＫＡ）引起皮层神经元毒性作用的影响及可能的作用机制。方法：在小鼠原代培养的皮层神经元ＫＡ毒性模型上,采用形态学观察,ＭＴＴ比色分析,ＥＬＩＳＡ及单细胞内游离钙离子浓度测定等方法。结果：ＥＧｂ７６１（６２．５μｇ／ｍｌ）及内酯Ｂ（３７．５μｇ／ｍｌ）预处理２４ｈ可不同程度地对抗ＫＡ（０．５ｍｍｏｌ／Ｌ）短时间作用引起神经元损伤。结论：ＥＧb761可部分对     

乙肝疫苗接种无、弱应答与遗传因素关系

从现场流行病学和实验研究两方面探讨乙肝疫苗接种无、弱应答是否与遗传因素有关。方法健康小学生６３４名接种３针血源性乙肝疫苗,共筛选出２９我、弱应答,同时选择３０名强应答作为对照,对无、弱应答和强应答一级亲属中符疫苗接种条件的对象接种３针乙肝疫苗,观察免疫反应。另外,从无、弱应答和强应答中选择部分对象检测了人类白细胞抗原（ＨＬＡ）－Ａ,Ｂ,Ｃ,ＤＲ,ＤＱ座位等位基因。结果小学生无、弱应答率为     

聚乳酸酮洛芬微球的制备及其体外释放度

制备了生物可降解的材料聚乳酸,用粘度法测定其分子量,并选用Ａ、Ｂ、Ｃ三种不同分子量的聚乳酸为药物的载体,制备了酮洛芬微球（ＡＳ,ＢＳ,ＣＳ）,测定其粒径和体外溶出速率。结果表明催化剂四苯基锡用量增加,所得的聚乳酸分子量增加,而制备酮洛芬微球的聚乳酸分子量越大,其微球粒径越大,溶出速率越小。