Improvement of hepatic fibrosis after tenofovir disoproxil fumarate switching to tenofovir alafenamide for three years

BACKGROUND Both tenofovir alafenamide(TAF)and tenofovir disoproxil fumarate(TDF)are the first-line treatments for chronic hepatitis B(CHB).We have showed switching from TDF to TAF for 96 weeks resulted in further alanine aminotransferase(ALT)improvement,but data remain lacking on the long-term benefits of TDF switching to TAF on hepatic fibrosis.AIM To assess the benefits of TDF switching to TAF for 3 years on ALT,aspartate aminotransferase(AST),and hepatic fibrosis improvement in patients with CHB.METHODS A single center retrospective study on 53 patients with CHB who were initially treated with TDF,then switched to TAF to determine dynamic patterns of ALT,AST,AST to platelet ratio index(APRI),fibrosis-4(FIB-4)scores,and shear wave elastography(SWE)reading improvement at switching week 144,and the associated factors.RESULTS The mean age was 55(28-80);45.3%,males;15.1%,clinical cirrhosis;mean baseline ALT,24.8;AST,25.7 U/L;APRI,0.37;and FIB-4,1.66.After 144 weeks TDF switching to TAF,mean ALT and AST were reduced to 19.7 and 21,respectively.From baseline to switching week 144,the rates of ALT and AST<35(male)/25(female)and<30(male)/19(female)were persistently increased;hepatic fibrosis was also improved by APRI<0.5,from 79.2%to 96.2%;FIB-4<1.45,from 52.8%to 58.5%,respectively;mean APRI was reduced to 0.27;FIB-4,to 1.38;and mean SWE reading,from 7.05 to 6.30 kPa after a mean of 109 weeks switching.The renal function was stable and the frequency of patients with glomerular filtration rate>60 mL/min was increased from 86.5%at baseline to 88.2%at switching week 144.CONCLUSION Our data confirmed that switching from TDF to TAF for 3 years results in not only persistent ALT/AST improvement,but also hepatic fibrosis improvement by APRI,FIB-4 scores,as well as SWE reading,the important clinical benefits of long-term hepatitis B virus antiviral treatment with TAF.

Pre-Formulation Development of Lamivudine 300 mg and Tenofovir Disoproxil Fumarate (TDF) 300 mg Fixed Dose Combination Tablets

Introduction: In this study, physical and chemical characteristics of Lamivudine, Tenofovir Disoproxil Fumarate (TDF) and potential excipients were systematically followed and documented [1]. Objective: The objective of this scientific work was to carry out pre-formulation studies including compatibility studies on Lamivudine and Tenofovir Disoproxil Fumarate with their potential excipients prior a direct compression process [2]. Methodology: The interaction was studied in three set of environments namely uncontrolled room conditions for Zone VI b (30°C ± 2°C), oven conditions in which the oven was set at 50°C and accelerated climatic conditions in which a climatic chamber was set at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %). Sample preparation was done by mixing the amount of formulation excipients to active substances at a ratio of 1:10, whereas active substance to another active substance at a ratio of 1:1, active substance to coating materials at 1:4, coating materials to the whole set of excipients 1:4. The whole set of samples was geometrically mixed and triturated by mortar and pestle to very fine uniform powder to ensure homogeneity of the mixture. HPLC analytical method was used for simultaneous quantitative determination of lamivudine and tenofovir disoproxil fumarate. Transmittance of the mixture was determined by Near Infra-Red (NIR) technique. Results: The amount of Lamivudine as on day 0 was comparable to day 90 for in all tested conditions (Room, Oven and Climatic Chamber), whereas for Tenofovir Disoproxil Fumarate only the amount of the drug at Room (30°C ± 2°C) was comparable to results on day 90. A significant drop of amount of Tenofovir Disoproxil Fumarate (TDF) exposed to moisture (Climatic chamber at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %)) and temperature of 50°C was observed. Colour change was observed for samples subjected to moisture (Climatic chamber at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %)) and as well picked up in the NIR region 400 to 1500 cm-1 (Finger print region) by a significant shift in Transmittance. Conclusion: It can be concluded that microcrystalline cellulose, cross linked sodium carboxymethyl cellulose, magnesium stearate and sodium carbxymethyl cellulose can be compressed together with Lamivudine and Tenofovir Disoproxil Fumarate (TDF) to produce a pharmaceutically acceptable solid dosage form, tablet. The produced tablets should be packed in moisture and light protective containers as Tenofovir Disoproxil Fumarate (TDF) has diester linkages which can be hydrolysed into the active drug Tenofovir in the presence of moisture.

Treatment of Chronic Hepatitis B with Tenofovir Disoproxil Fumarate in Ivory Coast

Little data exist on patients treated with tenofovir in Sub-Saharan Africa. Objective: To describe the clinical and laboratory characteristics of patients with viral hepatitis B treated with tenofovir. Material and methods: A descriptive single-center retrospective study, on chronic viral hepatitis B mono-infected, followed in the hepatogastroenterology department of the University Hospital of Yopougon and treated with tenofovir from February 2012 to February 2015. The studied parameters were demographic, clinical, biochemical, serological, virological, abdominal ultrasound. Liver fibrosis was assessed either by liver biopsy or non-invasive tests. Results: 110 patients were treated with tenofovir disoproxil fumarate with a mean age of 40.4 years and a male predominance. Clinical examination revealed jaundice in 9% of cases, hepatomegaly in 7.3% of cases, splenomegaly in 9.1% of cases and ascites in 15.5% of cases. The AST averaged 77.3 IU/l, the ALT 76.8 IU/l, prothrombin rate at 76.6% , albumin level at 32.3 g/l, total bilirubin at 29.9 g/l, alpha fetoprotein rate at 15.3 ng/ml. HBe antigen was negative in 76.2% of cases. The average rate of DNA at baseline was 7.4 log10 IU/l. 27.5% was cirrhotic. The average time of starting treatment was 23.7 months. Conclusion: TDF is the first-line treatment for chronic hepatitis B in our country, because it is a well-tolerated, potent therapy with a high threshold for resistance development. Our study population had an average age of 40.4 years. Virological profile was dominated by HBe antigen negative patients and high viral load of HVB DNA. One third of patients were at the stage of cirrhosis. This treatment must be delivered free of charge in all the country hospitals, which is going to improve significantly the natural evolution of the disease and to decrease the incidence of the HCC.

Influence of Solvent Polarity on the Physio-Chemical Properties and Quantitative Determinations of Tenofovir Disoproxil and Emtricitabine with Chloranilic Acid as Complexing Agent

Purpose: Tenofovir disoproxil fumarate (TEN) and emtricitabine (EMT) are both second generation ant-retroviral drugs used in the “treatment” of HIV/AIDS. The aim of this study is to establish the physic-chemical properties of their reaction with chloranilic acid in different solvent systems and to justify the chemical basis for simultaneous quantitative determination of these drugs in their combined formulation. Method: TEN and EMT were individually isolated from their single formulations and purified by chromatography to obtain secondary standard. Purity of the isolates were tested for by comparison with literature values. Stock solution of chloranilic acid (CA) [3.0 × 10﹣3 M] was prepared in the following solvents of different polarities: ethanol, acetonitrile, ethylacetate, chloroform and hexane. Equal volumes of CA and TEN [3.0 × 10﹣2 M] and EMT [3.0 × 10﹣2 M] dissolved in different solvents were mixed whereby colored products were observed. Absorption maxima were determined. Calibration curves were generated and validated. Quantitative simultaneous determination of TEN and EMT was determined by standard protocol. Stoichiometric relationships between the drugs and CA were established. Equilibrium constants were determined at different temperatures from which the Gibb’s free energies were calculated. Arrhenius equation was used to calculate the enthalpy, entropy was similarly calculated. Results: Absorption maxima of CA in different solvents are as follows: Ethanol 310 nm;Acetonitrile 330 nm;Ethyl acetate 340 nm;Chloroform 350 nm and hexane 310 nm. The complex of CA and TEN in the different solvents are: Alcohol 525 nm, Acetonitrile 500 nm;Ethyl acetate 505 nm;Chloroform 510 nm and hexane 515 nm. For EMT complex absorption maxima are: Alcohol 510 nm;Acetonitrile 515 nm’ Ethyl acetate 520 nm’ Chloroform 505 nm and hexane 530 nm. Simultaneous quantitative recovery values for TEN are: Ethanol;97.89% ± 1.21;Acetonitrile 101.17 V 1.51%;Ethyl acetate 96.55% ± 0.71%;Chloroform 99.11% ± 0.34% and hexane 98.03% ± 0.15%. For EMT the values are also: Ethanol: 98.92% ± 1.45%;Acetonitrile 100.471 ± 13;Ethyl acetate 97.06% ± 0.87%;Chloroform 99.31% ± 0.94% and Hexane 99.97% ± 1.63%. Stoichiometry of complexation showed a 1:1 ratio for both drugs. Equilibrium constants for TEN were highest in acetonitrile and least for Ethanol while for EMT, equilibrium constant was least for acetonitrile and highest in chloroform. Gibb’s free energy for TEN was least in ethanol and highest in acetonitrile. Gibb’s free energy for EMT was least in acetonitrile and highest in chloroform. Enthalpy for TEN was least in chloroform and highest in hexane. Similarly, the enthalpy for EMT was highest in chloroform and lowest in hexane. Conclusion: These results shows that solvent polarity influence charge transfer complexes in a non consistent fashion. The structure of the donor might have contributed to thermodynamics of complexation since orbital overlap may vary from solvent to solvent. For quantitative analysis hexane appears to be the most suitable solvent because it has the highest molar absorptivity and higher enthalpy of interactions. Molecules that can donate electrons and their stereochemistry could contribute to intensity of absorption maxima of the electronic transitions.

Differences of Efficacy Between Tenofovir Alafenamide Fumarate and Tenofovir Disoproxil Fumarate in Pregnant Women With Different Hepatitis B Virus DNA Loads

Tenofovir alafenamide fumarate(TAF)has been endorsed by guidelines for blockade ofmother-to-child transmission of hepatitis B virus(HBV),given that its efficacy and safety are comparable to tenofovir disoproxil fumarate(TDF).However,there is a lack of comparative studies regarding the treatment efficacy in patients with diverse viral loads.This study retrospectively analyzed 96 hepatitis B e antigen(HBeAg)–positive pregnant women with HBV DNA levels of≥2×10^(5) IU/mL.Based on viral loads(HBV DNA levels),participants in the TAF and TDF groups were stratified into three subgroups,namely,the High-G(titer≥8 log_(10) IU/mL),Middle-G(7 log_(10) IU/mL≤titer<8 log_(10) IU/mL)and Low-G(titer<7 log_(10) IU/mL)subgroups.The primary endpoint was effectiveness of TAF and TDF in patients with varying viral loads,whereas secondary endpoints were hepatitis B surface antigen(HBsAg)positivity in infants at 7 to 12 months and the safety profile for mothers and children.Compared with baseline levels,median HBV DNA levels in mothers were decreased by 4.51 and 4.09 log_(10) IU/mL in the TAF andTDF groups(P=0.04)predelivery,respectively.In the High-G subgroup,the titers were significantly lower in the TAF group(P=0.045).A higher proportion of patients experienced a virus decline of≥4 log_(10) IU/mL in the TAF group compared with the TDF group,with rates of 78.26% versus 58%(P=0.034),respectively.Moreover,the median serum phosphate levels significantly decreased frombaseline to predelivery in the TDF group(P=0.04).Finally,infants in both cohorts tested negative for HBsAg at 7–12 months after delivery.Overall,our findings indicate that TAF can be considered the preferred option for the treatment of HBeAgpositive pregnant women with HBV DNA levels of≥8 log_(10) IU/mL.

TDF+3TC+EFV和AZT+3TC+EFV方案治疗96周对初治HIV感染者肾功能的影响

目的探讨应用我国首选抗 HIV 治疗方案富马酸替诺福韦二吡呋酯(tenofovir disoproxil fumarate, TDF)+拉米夫定(lamivudine, 3TC)+依非韦伦(efavirenz, EFV)及备选方案齐多夫定(zidovudine, AZT)+3TC+EFV 对初治 HIV 感染者肾功能的影响。方法回顾性分析 2012 年 1 月—2014 年 5 月在上海市公共卫生临床中心艾滋病门诊使用上述 2 种方案抗病毒治疗并随访的初治 HIV 感染者 1045 例,其中应用 TDF+3TC+EFV 方案(TDF 组) 455 例,AZT+3TC+EFV 方案(AZT 组)590 例。收集患者人口学资料及临床治疗数据,分析 2 组治疗过程中肾功能指标变化情况。结果 TDF 组的基线、治疗 48 周、96 周估算肾小球滤过率(estimated glomerular fi ltration rate, eGFR)分别是 113.1 ml/(min·1.73 m^2),114.0 ml/(min·1.73 m^2)和 112.2 ml/(min·1.73 m^2);AZT 组的基线、治疗 48 周、96 周 eGFR 分别是 112.9 ml/(min·1.73 m^2),116.2 ml/(min·1.73 m^2)和 118.1 ml/(min·1.73 m^2)。与治疗前相比,TDF 组治疗 48 周 eGFR 水平有稍微升高,而在治疗 96 周时又回落至基线水平。而 AZT 组,治疗 48 周及 96 周的 eGFR 水平与基线 eGFR 水平相比均有升高。TDF 组中基线 eGFR < 90 ml/(min·1.73 m^2)者,治疗 48 周 eGFR 水平较基线有上升;AZT 组中基线 eGFR < 90 ml/(min·1.73 m^2)者治疗 48 周 eGFR 水平较基线有所升高。结论我国初治 HIV 感染者中应用 TDF+3TC+EFV 方案治疗者,开始治疗的 2 年内患者肾功能无明显减低;对于 60 ml/(min·1.73 m^2)< eGFR < 90 ml/(min·1.73 m2)的初治 HIV 感染者,TDF 组治疗后 eGFR 亦保持稳定。关于 TDF 组远期治疗后肾功能变化有待于进一步观察。

Incident hepatocellular carcinoma developing during tenofovir alafenamide treatment as a rescue therapy for multi-drug resistant hepatitis B virus infection: A case report and review of the literature

Tenofovir disoproxil fumarate(TDF)is a potent nucleotide analogue with high barrier to resistance,which is recommended for multi-drug resistant hepatitis B virus(HBV)infection.However,nephrotoxicity has been reported during TDF treatment,and tenofovir alafenamide(TAF),which has comparable efficacy to TDF and improves bone and renal safety,can be used as a replacement strategy.Herein,we describe a clinical case concerning a 60-year-old individual suffering liver cirrhosis and renal dysfunction,and being infected with multidrug-resistant HBV.When failing treatment with TDF,he received TAF as a rescue therapy.TAF effectively inhibited HBV replication without worsening renal function or serum phosphorus abnormality.Furthermore,hepatocellular carcinoma(HCC)occurred during TAF treatment despite controlling the viral load.The risk of HCC could not be eliminated and should be monitored during TAF treatment.

Rapid Recovery in COVID-19 Patients with Chronic Hepatitis B Virus Infection Treated with Tenofovir Disoproxil Fumarate

The coronavirus disease 2019(COVID-19)pandemic continues worldwide.We report here two cases of chronic hepatitis B patients with acute respiratory syndrome coronavirus 2 infection treated with tenofovir disoproxil fumarate who demonstrated a favorable outcome.This report adds some evidence that concurrent HBV infection may not worsen COVID-19 infection and tenofovir disoproxil fumarate treatment may have partial positive effect on COVID-19 rapid recovery.

慢性乙型肝炎患者ETV/TDF应答不佳研究进展

乙型肝炎病毒(hepatitis B virus,HBV)感染严重危害人类健康,一线核苷(酸)类似物[nucleos(t)ide analogues,NAs]抗病毒治疗是目前临床广泛使用的有效治疗措施之一,但恩替卡韦(entecavir,ETV)/替诺福韦酯(tenofovir disoproxil fumarate,TDF)应答不佳降低了抗病毒治疗有效率。目前应答不佳评估标准尚未形成统一共识,亦缺乏明确的流行病学资料,对于应答不佳的原因、危害有待进一步研究,治疗策略仍有待验证。本文主要就ETV/TDF应答不佳的评估标准、原因、危害及NAs治疗方案进行综述。

TDF转换为TAF治疗病毒学应答后CHB的疗效和安全性研究

目的:探究TAF治疗CHB患者的疗效及安全性。方法:回顾性分析某院2018年11月~2019年5月期间收治的132例TDF治疗48周以上,病毒已应答的慢性乙型肝炎患者,以续贯治疗药物的不同作为分组依据,将继续使用TDF的患者纳入对照组,TDF转换为TAF的患者纳入实验组各66例,记录两组治疗基线时间及48周后临床数据并进行分析。结果:两组在基线上,ALT、AST、Cr、UA、β2-MG、CHOL、TG、LDL-C、FS无统计学差异,实验组Uβ2-MG(1.21±0.149 mg/L)明显高于对照组(0.46±0.057 mg/L),且具有统计学意义(P<0.001);两组在48周时,ALT、AST、Cr、UA、β2-MG、Uβ2-MG、TG、FS无统计学差异,实验组CHOL、LDL-C(4.88±0.719、2.90±0.578)明显高于对照组(4.41±0.696、2.70±0.389),且均具有统计学意义(P<0.05)。两组均未出现病毒学突破表现。结论:对于TDF经治的CHB患者,换用TAF的疗效不劣于TDF持续治疗,在肾小管安全性上具有优势,但需注意血脂异常。

Efficacy of tenofovir alafenamide in treatment of hepatitis B virus:A meta-analysis and non-inferiority evaluation

Objective:To evaluate the effect of tenofovir alafenamide versus tenofovir disoproxil fumarate on antiviral efficacy in patients with hepatitis B virus infection.Methods:Randomized controlled trials were searched on CNKI,Wanfang,VIP,China Biomedical Literature Database,PubMed,Cochrane Library,Embase,ClinicalKey,Chinese Clinical Trial Registry and ClinicalTrials.gov from the date of inception to April 2020.The literature was screened according to the inclusion and exclusion criteria,and the efficacy evaluation index of the included RCT was set as the success rate of reaching the endpoint of viral suppression and achieving normalized ALT values at 48 weeks of treatment.Intentionality analysis was adopted and the analysis results were taken as the final conclusion.RevMan 5.3 software was used for this Meta-analysis.Meanwhile,VassarStats was used to evaluate the non-inferiority of TAF and calculate the difference of virus inhibition efficiency rate and 95%confidence interval between experimental group and the control group of each RCT.Results:After the literature search,411 potential articles were found,5 studies were finally included according to the criteria,and 2,120 patients were included.Intentionality analysis showed that TAF regimen and TDF regimen had similar viral suppression success rates(RR=0.97,95%CI:0.94~1.01,P=0.19).The ALT normalization rate in the TAF treatment group was higher than that in the TDF treatment group,and the difference was statistically significant(RR=1.35,95%CI:1.20-1.53,P<0.00001).The non-inferiority margin was set at 10%,and it was found that three RCT studies in the international multi-center all showed that TAF was not inferior to TDF in controlling HBV viral load,while two RCT studies in China's Mainland failed to achieve non-inferiority after calculation.Conclusions:At 48 weeks of treatment,TAF was similar to TDF in controlling HBV viral load.However,the efficacy of TAF in controlling HBV viral load may vary among different populations,which requires further confirmation by more clinical trial evidence.Based on AASLD criteria,the ALT normalization rate of the TAF group was higher than that of the TDF group at 48 weeks of treatment,showing an obvious advantage.

复方栀子根颗粒联合替诺福韦酯对慢性乙型肝炎患者血清细胞因子水平的影响

目的:观察复方栀子根颗粒联合替诺福韦酯(TDF)治疗慢性乙型肝炎(CHB)患者的临床疗效及对细胞因子的影响。方法:纳入CHB初治患者80例,采用临床随机对照研究,除去脱落及剔除病例,共纳入分析75例(治疗组35例、对照组40例)。对照组患者给予口服TDF,治疗组患者在对照组基础上加用复方栀子根颗粒,两组患者均在治疗4周、24周时比较肝功能(ALT、AST、GGT)变化,在治疗24周比较病毒学指标(HBV DNA、HBsAg、HBeAg)、细胞因子(IL-6、IL-10、IL-17、IL-23)水平及临床疗效判定。结果:两组患者治疗24周后肝功能、病毒学指标、细胞因子水平均较治疗前显著降低(P<0.05)。组间比较,治疗4周后治疗组转氨酶下降水平更低,差异有统计学意义(Z=-2.90,P=0.004;Z=-3.26,P=0.001;Z=-2.24,P=0.025);治疗组24周时IL-6、IL-23水平较对照组低,差异有统计学意义(Z=-2.14,P=0.033;Z=-2.10,P=0.036);治疗组总有效率97.14%(34/35),对照组95.00%(38/40),治疗组总有效率高于对照组(χ2=9.49,P=0.019);治疗组较对照组不良反应更少,差异有统计学意义(χ2=6.19,P=0.044)。结论:复方栀子根颗粒联合TDF治疗早期能更快降低转氨酶水平,降低促炎细胞因子水平及提高临床综合疗效优于单用TDF,并减轻临床不良反应。

富马酸丙酚替诺福韦对高病毒载量慢性乙型肝炎病毒感染母婴阻断的分析

目的对比富马酸丙酚替诺福韦(TAF)、富马酸替诺福韦二吡呋酯(TDF)用于慢性乙肝病毒(HBV)感染的高病毒载量母婴阻断有效性及安全性。方法前瞻性选取高病毒载量孕妇116例,分为TAF组(56例)和TDF组(60例),在第24~28孕周开始服药,两组均分别在24~28孕周、32~36孕周及分娩时检测HBV DNA、HBsAg和HBeAg,新生儿分别在出生时、7月龄时检测HBV DNA、HBsAg和HBeAg。结果分娩时两组孕妇血清HBV DNA降至2.0×10~5 IU/mL以下的病例数,TAF组占92.9%,TDF组占95%;TAF组57例新生儿(1例为双胞胎),出生时HBsAg阳性4例,占7.01%,HBV DNA阳性1例,占1.75%,TDF组60例新生儿,出生时HBsAg阳性2例,占3.33%,HBV DNA均阴性。两组新生儿7月龄时HBsAg、HBV DNA均阴性,均产生抗HBs,阻断成功率100%,两组孕妇均未见明显不良反应,新生儿出生时、28、48、96周均未见明显生长发育障碍。结论TAF用于慢性HBV感染的高病毒载量的母婴阻断有效且安全。

基于真实世界数据的不同用药方案对艾滋病患者血脂水平的影响分析

目的:基于真实世界数据分析不同用药方案对艾滋病患者血脂的影响。方法:基于医院信息系统(HIS)中真实世界数据,采用分层随机抽样法选取本省16家三级甲等医院,收集2022年1月至7月在上述医院中采用不同用药方案的702例艾滋病患者的病历资料,根据其采用的用药方案分为方案1组[拉米夫定(3TC)+齐多夫定(AZT)+依非韦伦(EFV)]、方案2组[3TC+AZT+奈拉伟平(NVP)]、方案3组[3TC+富马酸替诺福韦酯(TDF)+EFV]和方案4组(3TC+TDF+NVP)。比较各组患者治疗前、治疗6个月后的空腹血脂[总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)]水平和血脂异常率;比较各组患者用药期间血脂变化导致不良事件的发生情况。结果:治疗后,各组患者TC、TG、LDL-C水平及血脂异常率高于治疗前,HDL-C水平低于治疗前,且方案3组、方案4组患者TC、TG、LDL-C水平及血脂异常率分别低于方案1组、方案2组,HDL-C水平分别高于方案1组、方案2组(均P<0.05);方案3组、方案4组患者用药期间血脂变化导致不良事件的发生率分别低于方案1组、方案2组(均P<0.05)。结论:与3TC+AZT+EFV、3TC+AZT+NVP治疗方案相比,3TC+TDF+EFV、3TC+TDF+NVP治疗方案可降低艾滋病患者TC、TG、LDL-C水平,提高HDL-C水平,改善血脂异常,减少血脂异常导致的不良事件。

替诺福韦对肝星状细胞活化及CCR2表达水平的影响

目的:研究药物替诺福韦(TDF)对人肝星状细胞(LX-2)的CC趋化因子受体2(CCR2)表达的影响,探讨TDF在肝纤维化疾病发展中发挥抗纤维化的作用机制。方法:以LX-2作为体外实验研究对象,使用HE染色观察用药后细胞增殖情况。利用蛋白质印迹法检测使用不同浓度TDF和CCR2小干扰RNA(siRNA)对LX-2细胞α平滑肌肌动蛋白(α-SMA)及CCR2蛋白表达水平的影响。结果:siRNA沉默CCR2表达可显著下调肝纤维化相关蛋白α-SMA表达(P<0.01);TDF抑制LX-2细胞的增殖活化,明显降低细胞CCR2及α-SMA的蛋白表达水平(P<0.01)。结论:TDF可通过抑制CCR2表达抑制肝星状细胞活化,发挥抗肝纤维化作用。

恩替卡韦、富马酸替诺福韦二吡呋酯及富马酸丙酚替诺福韦治疗慢性乙型肝炎的疗效及安全性分析

目的观察恩替卡韦(entecavir,ETV)、富马酸替诺福韦二吡呋酯(tenofovir disoproxil fumarate,TDF)及富马酸丙酚替诺福韦(tenofovir alafenamide fumarate,TAF)抗病毒治疗慢性乙型病毒性肝炎(慢乙肝)的临床疗效及安全性。方法选择2021年3月—2023年6月我院收治的181例慢乙肝患者,依据抗病毒治疗用药不同分为3组,ETV组(n=66)、TDF组(n=64)及TAF组(n=51)。比较3组患者的血脂、肝功能、HBsAg、HBV DNA、血肌酐及估算的肾小球滤过率(estimated glomerular filtration rate,eGFR)等指标在治疗前后及组间的差异。结果ETV组有效率为86.36%(57/66),TDF组有效率为90.63%(58/64),TAF组有效率为90.20%(46/51),3组比较差异无统计学意义(P>0.05)。治疗后,3组的HBsAg水平、HBV DNA载量均低于治疗前(P均<0.05),且3组间HBsAg水平、HBV DNA载量的变化幅度比较,差异具有统计学意义(P<0.05)。治疗后,3组的ALT、AST水平均低于治疗前(P均<0.05),且3组间ALT、AST水平的变化幅度比较,差异有统计学意义(P<0.05)。治疗后,ETV组的HDL-C、LDL-C均高于治疗前(P均<0.05),TC、TG较治疗前差异均无统计学意义(P均>0.05);TDF组的TC、HDL-C均低于治疗前(P均<0.05),TG、LDL-C较治疗前差异均无统计学意义(P均>0.05);TAF组的TC、TG、HDL-C、LDL-C较治疗前差异均无统计学意义(P均>0.05),但3组间TC、TG、HDL-C、LDL-C的变化幅度比较,差异均有统计学意义(P均<0.05)。治疗后,3组的血肌酐、eGFR较治疗前差异均无统计学意义(P均>0.05),但3组间血肌酐、eGFR的变化幅度比较,差异均有统计学意义(P均<0.05)。结论ETV、TDF、TAF治疗慢乙肝的临床疗效相近,服用TAF不会对血脂造成影响,但服用ETV会引起HDL-C、LDL-C水平升高,服用TDF可降低TC、HDL-C水平,并且均有较好的肾脏安全性。

清热利湿化浊方在治疗慢性乙型肝炎肝硬化中作用及对肝功能和乙型肝炎病毒定量的影响

目的探讨清热利湿化浊方联合富马酸替诺福韦二吡呋酯片治疗慢性乙型肝炎病毒(乙肝)(Hepatitis B virus,HBV)肝硬化的疗效及对肝功能和乙肝病毒定量的影响。方法选择医院于2020年5月—2022年5月慢性乙肝肝硬化患者82例,运用随机表法分为观察组41例与对照组41例。对照组给予富马酸替诺福韦二吡呋酯片治疗,观察组在富马酸替诺福韦二吡呋酯片基础上结合清热利湿化浊方治疗。两组治疗疗程24周。比较两组治疗24周临床疗效;治疗前后肝功能,肝纤维化,乙肝病毒脱氧核糖核酸(hepatitis B virus deoxyribonucleic acid,HBV DNA)载量,炎性因子,Toll样受体4(Toll-like receptor4,TLR4)和c-Jun氨基末端激酶(c-Jun N-terminal kinase Messenger RNA,JNK)mRNA表达。结果观察组总有效率高于对照组(P<0.05)。两组治疗后天冬氨酸氨基转移酶(Aspartate aminotransferase,AST)、总胆红素(Total bilirubin,TBIL)和丙氨酸氨基转移酶(Alanine aminotransferase,ALT)水平低于治疗前(P<0.05);观察组治疗后AST、TBIL和ALT水平低于对照组(P<0.05)。两组治疗后透明质酸(Hyaluronic acid,HA)、层黏连蛋白(Laminin,LN)、Ⅲ型前胶原(Procollagen typeⅢ,PCⅢ)和Ⅳ型胶原(Collagen type IV,CⅣ)水平低于治疗前(P<0.05);观察组治疗后HA、LN、PCⅢ和CⅣ水平低于对照组(P<0.05)。两组治疗后HBV DNA载量低于治疗前(P<0.05);观察组治疗后HBV DNA载量低于对照组(P<0.05)。两组治疗后白介素(interleukin,IL)-6、IL-8和肿瘤坏死因子-α(tumor necrosisfactor-α,TNF-α)水平低于治疗前(P<0.05);观察组治疗后IL-6、IL-8和TNF-α水平低于对照组(P<0.05)。两组治疗后TLR4和JNK mRNA表达低于治疗前(P<0.05);观察组治疗后TLR4和JNK mRNA表达低于对照组(P<0.05)。结论清热利湿化浊方联合富马酸替诺福韦二吡呋酯片治疗慢性乙肝肝硬化患者疗效显著,且可改善患者肝功能,降低乙肝病毒载量,减轻炎症反应,及下调TLR4/JNK信号传导通路。

富马酸替诺福韦酯和富马酸丙酚替诺福韦序贯联合聚乙二醇干扰素α-2b治疗慢性乙型肝炎患者的疗效比较

目的:比较富马酸替诺福韦酯(tenofovir disoproxil fumarate,TDF)和富马酸丙酚替诺福韦(tenofovir alafenamide fumarate,TAF)两种药物序贯加用聚乙二醇干扰素α-2b在慢性乙型肝炎患者中的疗效。方法:选取慢性乙型肝炎患者160例,根据用药方案不同分成实验组和对照组各80例,分别接受TAF治疗和TDF治疗,均治疗24周后加用聚乙二醇干扰素α-2b治疗72周。观察指标包括HBV-DNA阴转率、HBeAg阴转率、HBsAg阴转率、HBsAg滴度、HBVDNA定量和ALT水平。结果:共有128例参与者完成了研究,其中实验组62例,对照组66例。96周时,实验组的HBsAg转化率、HBsAg滴度和HBVDNA定量明显优于对照组,差异有统计学意义(P<0.05)。实验组的HBVDNA清除率和e抗原转化率也高于对照组,但差异接近显著(P=0.058和P=0.085)。实验组的ALT值在72周和96周时均低于对照组,差异有统计学意义(P<0.05)。结论:TAF联合长效干扰素治疗慢性乙型肝炎疗效明显优于TDF联合长效干扰素,可以有效改善患者的病毒学指标和肝功能,是一种更为有效的治疗方案。

富马酸替诺福韦在治疗低病毒载量慢性乙肝患者中的效果分析

目的探究低病毒载量慢性乙肝(CHB)患者的治疗期间应用富马酸替诺福韦(TDF)的价值。方法选取南阳医学高等专科学校第一附属医院2021年4月至2024年1月期间医院感染性疾病科诊治的72例低病毒载量CHB患者,其均符合低病毒载量的治疗标准,依据用药计划的差异,将其分为研究组(n=36,TDF)、对照组(n=36,常规治疗),比较两组疗效、肝功能指标、肝纤维化指标以及恢复情况。结果治疗后,研究组治疗有效率(97.22%)显著高于对照组(75.00%),差异有统计学意义(P<0.05);治疗前,两组肝功能、肝纤维化指标比较差异无统计学意义(P>0.05),治疗后,两组肝功能、肝纤维化指标均降低,且研究组低于对照组,差异有统计学意义(P<0.05);治疗后,研究组乙肝病毒-脱氧核糖核酸(HBV-DNA)转阴率、乙肝e抗原(HBeAg)转阴率、血清丙氨酸氨基转移酶(ALT)复常率均高于对照组,差异有统计学意义(P<0.05)。结论低病毒载量CHB患者治疗期间应用TDF较为理想,能够提升临床疗效,改善总胆红素、ALT等肝功能相关指标,进而优化HBV-DNA转阴率、HBeAg转阴率、ALT复常率,具有临床应用意义。