Effect of Pegylated Interferon Plus Tenofovir Combination on Higher Hepatitis B Surface Antigen Loss in Treatment-naive Patients With Hepatitis B e Antigen -positive Chronic Hepatitis B: A Real-world Experience

PurposeThe loss of serum hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B (CHB) is considered an ideal clinical outcome but rarely achieved with current standard of care. We evaluated the effectiveness in inducing HBsAg seroclearance in a real-world clinical cohort of Chinese patients with CHB treated with a combination of pegylated interferon (Peg-IFN) with tenofovir disoproxil fumarate (TDF) or monotherapy with each agent.MethodsA total of 330 patients with CHB were assigned to receive Peg-IFN plus TDF for 48 weeks (Peg-IFN plus TDF group), Peg-IFN alone for 48 weeks (Peg-IFN group), or TDF alone for 144 weeks (TDF group). The primary end point was the percentages of patients who achieved HBsAg seroclearance at week 72. Differences from the baseline characteristics and treatment data were compared using the χ² test for categorical variables or 1-way ANOVA for continuous variables. A Kaplan–Meier test was performed to compare the HBsAg loss among the 3 groups. Discrimination of responders versus nonresponders was quantified using AUC curves. Optimal cut-offs were selected based on Youden's J statistic defined as J = sensitivity + specificity-1.FindingsAt week 72, the Kaplan–Meier cumulative HBsAg loss was 11.5% in the Peg-IFN plus TDF group, 5.7% in the Peg-IFN group, and 0% in the TDF group. The percentage of patients with HBsAg loss was comparable in the Peg-IFN plus TDF and Peg-IFN groups (P = 0.143), but both were significantly higher than that in the TDF group (P = 0.000 and P = 0.010). In addition, a significantly higher percentage of patients in the combination group and Peg-IFN group had serum HBsAg of <100 IU/mL compared with the TDF group (32.7% vs 23.6% vs 9.2%; P < 0.001) but no significant differences in the percentages of patients with HBsAg <1000 IU/mL, the undetectable serum HBV DNA and hepatitis B e antigen seroconversion. Our model predicted serum HBsAg loss at week 72 (AUC = 0.846) if the HBsAg level was reduced by > 1.5 log₁₀ IU/mL from baseline at treatment week 24, an optimal timepoint for prediction of HBsAg loss in this cohort.ImplicationsA 48-week course of Peg-IFN and TDF combination therapy led to profound reduction in serum HBsAg level, resulting in a significantly higher rate of HBsAg loss compared with TDF monotherapy. Patients with steep HBsAg decline >1.5 log₁₀ IU/mL at week 24 well signaled a higher probability of achieving HBsAg loss at week 72.     

G蛋白β3亚单位C825T基因多态性与富马酸比索洛尔降压疗效的相关性

 目的 探讨G蛋白β₃亚单位C825T基因多态性与富马酸比索洛尔降压疗效的相关性。方法 选择2018-10至2020-10在解放军总医院第一医学中心心内科住院或门诊就诊的轻、中度原发性高血压患者,均口服5 mg/d比索洛尔,进行GNβ₃-C825T基因型测定,依据基因型分为3组:CC组、CT组、TT组,每组150例,在3组受试者治疗7 d,1、3、6个月后进行随访,测定患者的富马酸比索洛尔药物代谢血药浓度;治疗前、治疗7 d,1、3、6个月后进行24 h动态血压监测,比较患者静息状态下收缩压及舒张压(SBP、DBP),24 h收缩压均数(24 h SBP)、24 h舒张压均数(24 h DBP)、白天收缩压均数(d SBP)、白天舒张压均数(d DBP)、夜间收缩压均数(n SBP)、夜间舒张压均数(n DBP)的组间差异;进行24 h动态心电图监测,比较24 h平均心率、窦性心律震荡水平。结果 治疗7 d,随访1、3、6个月TT组富马酸比索洛尔血药浓度均高于CC组及CT组,差异均有统计学意义(P＜0.05),CC组与CT组无统计学差异,3组组内不同时间血药浓度变化均无统计学差异;应用富马酸比索洛尔后,3组患者血压均有下降趋势,其中TT组降压效果＞CT组＞CC组,3组间血压下降水平有统计学差异(P＜0.05);治疗7 d后,动态心电图显示:3组患者心率有下降趋势,TT组＞CT组＞CC组,其中TT组与CT组、CC组比较有统计学差异(P＜0.05),CT组与CC组心率下降无统计学差异;TT组窦性心律震荡水平优于CT组、CC组。结论 G蛋白β₃亚单位C825T基因多态性与富马酸比索洛尔降压疗效之间具有相关性。     

Steady-State Amprenavir,Tenofovir, and Emtricitabine Pharmacokinetics Before and After Reducing Ritonavir Boosting of a Fosamprenavir/Tenofovir/Emtricitabine Regimen from 200 mg to 100 mg Once Daily (TELEX II)

Abstract

Purpose: Evaluate how reducing ritonavir (RTV) boosting from 200 mg to 100 mg once daily (QD) affects steady-state pharmacokinetics of components of a fosamprenavir (FPV)-based regimen. Methods: Prospective, open-label, pharmacokinetic study in 12 HIV-infected patients stabilized on FPV/RTV 1400 mg/200 mg + tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) 300 mg/200 mg QD (TELEX II). Pharmacokinetics were assessed by noncompartmental analysis at baseline and 4 weeks after RTV reduction to 100 mg QD. Results: Baseline median minimum plasma concentration (C_min) and area under the plasma concentration-time curve over 24 hours post dose (AUC_24h) were as follows: APV: 1,708 ng/mL, 84,260 h ? ng/mL; tenofovir: 53 ng/mL, 2,420 h ? ng/mL; FTC: 58 ng/mL, 9,190 h ? ng/mL; RTV: 80 ng/mL, 10,230 h ? ng/mL. Four weeks after reducing RTV, changes in C_min and AUC_24h were: APV: +26%, +0.6%; tenofovir: +77%, +30%; FTC: +188%, +13%; RTV –64%, –79%. Component plasma concentration ranges were consistent with historical values. Median APV C_min was 14.7-fold above the protein-binding-adjusted 50% inhibitory concentration of wild-type HIV. Four weeks after RTV reduction, HIV-1 RNA levels remained <50 copies/mL in all patients, median CD4+ count increased from 465 to 495 cells/mm³, and favorable lipid changes and no adverse events were observed. Conclusion: Reducing RTV boosting from 200 to 100 mg QD of FPV/TDF/FTC QD conferred no detrimental effect on APV, tenofovir, FTC, or RTV pharmacokinetics and maintained virologic suppression.     

液相色谱-质谱联用法测定人血浆中富马酸单甲酯药物浓度及应用

目的： 建立液相色谱-质谱联用（HPLC-MS/MS）法测定人血浆中富马酸单甲酯的方法,并应用于检测中国健康受试者血浆中富马酸单甲酯的浓度。方法： 血浆样品用醋酸铵稀释后经过96孔固相萃取板前处理,以含0.5%甲酸的水溶液和甲醇作为流动相,采用梯度洗脱方式在ACE Excel 3 C₁₈-AR（2.1 mm×50 mm）色谱柱上进行分离,每个样品分析时间为4 min。在电喷雾负电离模式下,多反应监测检测离子对m/z 129.0→m/z 85.0（富马酸单甲酯）和m/z 134.0→m/z 90.0（内标,富马酸单甲酯-d₅）。结果： 富马酸单甲酯线性范围为4~1 200 ng·mL^-1（r²>0.99）,定量下限为4 ng·mL^-1,日内和日间精密度RSD ≤ 9.7%,准确度相对偏差均在±4.2%以内,平均回收率RSD ≤ 6.6%,基质效应在98.3%~100.9%之间。稳定性实验中,各种储存条件不影响对药品浓度的准确测定。结论： 本方法运行时间短,灵敏度高,重复性好,适用于富马酸单甲酯血浆浓度定量检测。     

比索洛尔治疗老年高血压伴心功能不全患者的临床疗效观察

目的:观察富马酸比索洛尔治疗老年血压伴心功能不全患者的临床疗效。方法:将100例患者随机分为治疗组和对照组,各50例,对照组给予常规治疗,治疗组在常规治疗的基础上加用比索洛尔,疗程8周。观察其治疗前后血压、心率、左室质量指数(LVMI)、室间隔厚度(IVS)、左室后壁厚度(LVWP)、左室舒张末期容量(LVEDV)、左室收缩末期容量(LVESV)、射血分数(EF)和舒张功能指标(E/A),以及血浆脑钠素(BNP)、血管内皮生长因子(VEGF)和高敏C-反应蛋白(hs-CRP)、肝肾功能等血液生化指标。结果:治疗组患者治疗后收缩压、舒张压及心率均较治疗前明显降低(P<0.01),且治疗后的心功能各指标(除NYHA分级IV)均优于治疗前(P<0.05),其中LVEDV、LVESV、LVMI、EF和E/A优于对照组(P<0.05)。治疗组治疗后BNP、VEGF及hs-CRP较治疗前显著降低(P<0.01),且治疗组BNP水平显著优于对照组(P<0.01)。两组患者血常规及肝肾功能检查治疗前后均在正常范围,差异无统计学意义(P>0.05)。结论:比索洛尔治疗高血压伴心功能不全疗效确切且安全可靠。     

比索洛尔联合氨氯地平治疗对老年冠心病并高血压临床疗效及预后观察

目的分析比索洛尔联合氨氯地平治疗对老年冠心病并高血压临床疗效及预后观察。方法选择本院2018年1月-2019年1月收治的70例老年冠心病并高血压患者,随机分成两组,对照组35例使用比索洛尔治疗,研究组35例在对照组基础上添加氨氯地平治疗,对两组临床疗效及不良反应情况比较。结果治疗后,研究组显效21例,好转13例,研究组总有效率为97.14%,比对照组的82.85%高,差异具有统计学意义(P<0.05);研研究组患者不良反应发生率为8.57%,比对照组的25.71%低,差异具有统计学意义(P<0.05)。结论比索洛尔联合氨氯地平治疗老年冠心病并高血压患者,可减少患者不良反应,有效提高临床治疗疗效,临床上值得推广使用。     

氨氯地平联合比索洛尔对老年冠心病合并高血压患者心功能和血压的影响

目的:观察氨氯地平联合比索洛尔对老年冠心病合并高血压患者心功能和血压的影响。方法:选取144例老年冠心病合并高血压患者为研究对象,按照随机抽签法分为对照组和研究组各72例,对照组采用比索洛尔治疗,研究组采用氨氯地平联合比索洛尔治疗。比较两组患者的心功能变化、血压变化、治疗效果以及不良反应发生情况。结果:治疗后,两组患者的心功能指标和血压指标均优于治疗前,且研究组优于对照组,差异有统计学意义(P<0.05)。研究组的治疗总有效率高于对照组,差异有统计学意义(P<0.05)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:氨氯地平联合比索洛尔治疗老年冠心病合并高血压患者效果显著,可降低患者血压,缓解患者临床症状,改善患者的心功能,且安全性较高。     

丹蒌片联合比索洛尔治疗冠心病心绞痛的临床研究

目的探讨丹蒌片联合比索洛尔治疗冠心病心绞痛的临床疗效。方法选取2015年2月—2018年2月于天津市第三中心医院收治的冠心病心绞痛患者104例作为研究对象,随机分成对照组和治疗组,每组各52例。对照组口服富马酸比索洛尔片,1片/次,1次/d。治疗组患者在对照组治疗基础上口服丹蒌片,5片/次,3次/d。两组均连续治疗6周。观察两组患者的临床疗效标准和心电图疗效,比较两组患者ADL评分、硝酸甘油用量、颈动脉内中膜厚度(IMT值)、血清指标的变化情况。结果治疗后,对照组和治疗组的临床总有效率分别是76.92%、92.31%;心电图总有效率分别是82.69%、96.15%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者ADL评分均显著升高,而硝酸甘油用量及颈动脉IMT值均显著降低,同组治疗前后比较差异有统计学意义(P0.05);治疗后,治疗组ADL评分显著高于对照组,而硝酸甘油用量及颈动脉IMT值低于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组患者血清可溶性CD105(sCD105)、P选择素及氨基末端脑钠肽前体(NT-proBNP)水平均较治疗前显著降低,同组治疗前后比较差异有统计学意义(P0.05);治疗后,治疗组这些血清学指标显著低于对照组,两组比较差异有统计学意义(P0.05)。结论丹蒌片联合比索洛尔治疗冠心病心绞痛疗效显著,能显著改善患者生活质量水平,改善血清学相关指标,具有一定的临床推广应用价值。     

两种吸入剂对支气管哮喘患者肾上腺皮质功能、糖脂代谢的影响

目的探讨长期应用布地奈德福莫特罗吸入剂(160μg/4.5μg)对支气管哮喘患者的控制作用及对肾上腺皮质功能、糖脂代谢的影响。方法将78例支气管哮喘患者随机分成治疗组和对照组,治疗组给予布地奈德福莫特罗吸入剂(160μg/4.5μg),每日两次,对照组按需应用沙丁胺醇吸入剂,口服茶碱缓释片。观察周期为一年。两组患者在治疗前1天(T0)、一个月(T1)、三个月(T3)、六个月(T6)、12个月(T12),分别给予哮喘控制测试(asthma control test,ACT)评分,呼气峰流速(peak expiratory flow,PEF)日变异率检查,分别抽血测皮质醇、促肾上腺素皮质激素(ACTH),空腹血糖(FPG)、糖化血红蛋白(HbA1c)、甘油三酯、总胆固醇。结果治疗组患者ACT评分高于对照组(P0.05),治疗组患者PEF日变异率小于对照组(P0.05)。治疗组与对照组皮质醇、ACTH、FPG、HbA1c、总胆固醇、甘油三酯之间的差异无统计学意义(P0.05)。结论布地奈德福莫特罗吸入剂对支气管哮喘患者的控制有良好作用,长期应用对患者的肾上腺皮质功能、糖脂代谢无不良影响。