妊娠后期应用替诺福韦治疗血清HBV高载量孕妇阻断HBV母婴传播的疗效及安全性分析*

目的 探讨在妊娠后期应用替诺福韦抗病毒治疗阻断HBV高载量孕妇HBV母婴传播的效果及安全性。方法 2015年3月~2017年9月我院诊治的HBV高载量孕妇83例,其中56例在妊娠28周接受替诺福韦口服抗病毒药物至分娩结束,另27例未接受抗病毒治疗。两组新生儿在出生后立即注射乙肝免疫球蛋白（HBIG）和乙肝疫苗,在婴儿出生12个月时检测血清HBV DNA、HBeAg和HBsAg水平,判断感染阻断情况。结果 在分娩时,接受抗病毒治疗妇女血清HBV DNA水平为（3.9±0.7） lg IU/ml,显著低于未抗病毒组[（7.6±0.5） lg IU/ml,P小鱼0.05],血清HBsAg水平为（674.3±301.9） IU/ml,显著低于未抗病毒组[（1104.1±401.2） IU/ml,P小鱼0.05],血清HBeAg水平为（2059.8±996.4） s/co,显著低于对照组[（3479.4±1287.6） s/co,P小鱼0.05]; 抗病毒组HBV母婴传播阻断率为100.0%,显著高于未抗病毒组的81.5%（P小鱼0.05）;抗病毒孕妇均未出现因药物治疗而引起的不良反应,两组新生儿出生时各项生长发育指标比较差异无统计学意义（P大鱼0.05）。结论 在妊娠后期应用替诺福韦抗病毒治疗HBV高载量孕妇对阻断HBV母婴传播效果好,安全性高。     

替诺福韦联合安络化纤丸治疗HBeAg阴性慢性乙型肝炎患者疗效及其血清肝纤维化指标的变化研究*

目的 观察应用替诺福韦联合安络化纤丸治疗HBeAg阴性慢性乙型肝炎患者的疗效。方法 2015年3月~2017年5月我院诊治的HBeAg阴性慢性乙型肝炎患者68例,采用随机数字表法分为联合组和对照组,两组均为34例。给予对照组患者替诺福韦口服治疗,联合组患者在对照组治疗的基础上加用安络化纤丸口服治疗,两组均观察治疗48 w。采用ELISA法检测血清白细胞介素（IL）-6、IL-2、肿瘤坏死因子-α（TNF-α）水平,采用放射免疫法检测血清III型前胶原（PC-III）、透明质酸（HA）、层粘连蛋白（LN）和IV型胶原（IV-C）水平。结果 在治疗48 w末,联合组血清HA、LN、IV-C和PC-III水平分别为（94.5±31.5） ng/ml、（113.2±51.6） ng/ml、（72.4±20.3） g/L和（102.4±19.6） g/L,显著低于对照组[分别为（121.6±37.5） ng/ml、（132.5±53.8） ng/ml、（94.6±22.1） g/L和（134.7±21.5） g/L,P<0.05];联合组患者血清IL-2水平为（173.6±28.3） ng/L,显著高于对照组[（145.7±26.4） ng/L,P<0.05],而血清IL-6和TNF-α水平分别为（94.5±16.2） pg/ml和（26.6 6.8） pg/ml,显著低于对照组[分别为（112.6±17.8） pg/ml和（35.7±8.3） pg/ml,P<0.05];联合组血清HBV DNA转阴率为91.2%,与对照组的88.2%比,无统计学差异（P<0.05）;两组血清ALT复常率均为94.1%。结论 应用替诺福韦联合安络化纤丸治疗HBeAg阴性慢性乙型肝炎患者疗效显著,可有效降低血清肝纤维化指标和细胞因子水平,可能与减轻了肝内炎症反应有关。     

Rate of cardiovascular,renal and bone disease and their major risks factors in HIV-infected individuals on antiretroviral therapy in Spain

BackgroundThe life expectancy of HIV-infected individuals has dramatically improved with potent antiretroviral therapies. However, organ-specific toxicities of some antiretrovirals and persistent inflammation and immune activation due to residual virus replication account for a high burden of age-associated comorbidities in the HIV population.MethodsThe prevalence of overt cardiovascular, renal and bone diseases as well as their major risk factors were cross-sectionally examined during the year 2014 in the VACH cohort, a large nationwide population of HIV-infected individuals in Spain.ResultsA total of 10,897 HIV-infected patients were examined. Seventy-one point four percent were male and the mean age was 48 years. Mean time since HIV diagnosis was 15.8 years and mean time on antiretroviral therapy was 13.1 years. The proportion of patients with undetectable viral load was 87.1%, whereas 65.7% had CD4 counts >500 cells/mm³. Overall, cardiovascular, renal and bone disease were recorded in 4.7%, 5.9% and 2.8%, respectively. The prevalence of major risk factors was as follows: smoking 51.3%, alcohol abuse 7.8%, overweight/obesity 42.2%, diabetes 19.9%, dyslipidaemia 72.6%, hypertension 25.6%, and osteoporosis 11.1%. In the subset of patients older than 55 years-old (18%), all figures for overt disease and their major risk factors were significantly greater.ConclusionMajor age-related medical conditions and most of their risk factors are highly prevalent in HIV-infected individuals on long-term antiretroviral therapy in Spain. Preventive actions, including careful selection of antiretroviral agents, should be prioritized in the ageing HIV population.     

Future prospectives for the management of chronic hepatitis B

Chronic hepatitis B virus infection affects about 400 million people around the globe and causes approximately one million deaths a year. Since the discovery of interferon-α as a therapeutic option the treatment of hepatitis B has evolved fast and management has become increasingly complicated. The amount of viral replication reflected in the viral load (HBV-DNA) plays an important role in the development of cirrhosis and hepatocellular carcinoma. The current treatment modalities for chronic hepatitis B are immunomodulatory (interferons) and antiviral suppressants (nucleoside and nucleotide analogues) all with their own advantages and limitations. An overview of the treatment efficacy for both immunomodulatory as antiviral compounds is provided in order to provide the clinician insight into the factors influencing treatment outcome. With nucleoside or nucleotide analogues suppression of viral replication by 5-7 log10 is feasible, but not all patients respond to therapy. Known factors influencing treatment outcome are viral load, ALT levels and compliance. Many other factors which might influence treatment are scarcely investigated. Identifying the factors associated with response might result in stopping rules, so treatment could be adapted in an early stage to provide adequate treatment and avoid the development of resistance. The efficacy of compounds for the treatment of mutant virus and the cross- resistance is largely unknown. However, genotypic and phenotypic testing as well as small clinical trials provided some data on efficacy in this population. Discontinuation of nucleoside or nucleotide analogues frequently results in viral relapse; however, some patients have a sustained response. Data on the risk factors for relapse are necessary in order to determine when treatment can be discontinued safely. In conclusion: chronic hepatitis B has become a treatable disease; however, much research is needed to tailor therapy to an individual patient, to predict the sustainability of response and determine thebest treatment for those failing treatment.     

Assessing recovery of renal function after tenofovir disoproxil fumarate discontinuation

Impaired renal function caused by tenofovir disoproxil fumarate (TDF) is considered reversible by discontinuing TDF administration, but there are occasional cases of incomplete recovery. We investigated the recovery of renal function after the discontinuation of TDF. Subjects comprised patients who had been started on TDF but in whom it was later discontinued because of impaired renal function. We investigated renal function until 96 weeks after the discontinuation of TDF, and the duration of TDF administration, up to May 2010. TDF was discontinued because of impaired renal function in 21 of 766 patients (2.7%). Following discontinuation, a significant recovery was seen in eGFR (p = 0.003). The median duration of administration was 28 days (6-941 days) in 9 patients whose eGFR recovered to pre-administration levels, 405 days (250-1,379) in 7 patients in whom mild recovery was seen, and 1,110 days (421-1,470) in 5 patients in whom eGFR was much lower than at the time of discontinuation. A significant correlation was seen between the eGFR recovery rate and the duration of TDF administration. TDF administration was discontinued because of renal impairment in 2.7% of patients. The duration of TDF administration was short in patients whose renal function recovered to pre-administration levels, but patients in whom sufficient recovery was not seen after discontinuation had received TDF over long periods and included many whose renal function gradually declined, even after discontinuation. Recovery of renal function after discontinuation of TDF is likely affected by the duration of TDF administration.     

Fanconi syndrome-like tubular acidosis associated with a tenofovir-containing antiretroviral regimen in a human immunodeficiency virus-1-infected Asian woman

A 49-year-old, human immunodeficiency virus-1-infected Asian woman developed Fanconi syndrome-like tubular acidosis while taking tenofovir disoproxil fumarate (TDF)/emtricitabine plus lopinavir/ritonavir for 9 months. All of her symptoms and abnormalities in laboratory tests resolved completely after switching TDF/emtricitabine to zidovudine and lamivudine. We consider that TDF caused symptomatic tubular acidosis in the present case, one of the few that has been reported in Japan to date.     

Tenofovir Alafenamide for Pregnant Chinese Women With Active Chronic Hepatitis B: A Multicenter Prospective Study

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阿德福韦酯分别联合恩替卡韦或替诺福韦治疗rtA181V/T单位点突变的慢性乙型肝炎患者疗效初步研究*

目的 研究应用阿德福韦酯(ADV)分别联合替诺福韦(TDF)或恩替卡韦(ETV)治疗rtA181V/T单位点突变的慢性乙型肝炎(CHB)患者的疗效。方法 2017年1月～2020年1月我院感染病科收治的50例rtA181V/T单位点突变的CHB患者被随机分为ADV联合TDF治疗25例和ADV联合ETV治疗25例,治疗观察48 w。采用实时荧光定量PCR法检测血清HBV DNA载量,使用全自动生化分析仪检测血生化指标,包括β2-微球蛋白(β2-MG)和视黄醇结合蛋白(RBP),并计算估算的肾小球滤过率(eGFR)和内生肌酐清除率(Crcl),采用ELISA法检测血清HBsAg和HBeAg,使用流式细胞仪检测外周血T淋巴细胞亚群。结果 在治疗24 w和48 w,ADV联合TDF治疗组血清HBV DNA转阴率分别为100.0%和100.0%,与ADV联合ETV治疗组(分别为96.0%和96.0%)比,无显著性差异(P>0.05);血清AST水平分别为(49.2±5.5)U/L和(30.4±4.0)U/L,显著低于ADV联合ETV治疗组【分别为(55.3±7.0) U/L和(43.2±6.8) U/L,P<0.05】,血清ALT水平分别为(40.3±6.1) U/L和(39.1±4.3) U/L,显著低于ADV联合ETV治疗组【分别为(65.1±7.5)U/L和(45.3±6.1)U/L,P<0.05】,血清HBV DNA水平分别为(0.8±0.2)lg IU/mL和(2.0±0.4)lg IU/mL,显著低于ADV联合ETV治疗组【分别为 (2.9±0.3)lg IU/mL和(1.2±0.2) lg IU/mL,P<0.05】;外周血CD4⁺细胞百分比分别为(45.2±3.6)%和(48.3±4.2)%,CD4⁺/CD8⁺细胞比值分别为(1.4±0.2)和(1.8±0.1),显著高于ADV联合ETV治疗组【分别为(42.4±3.1)%和(45.0±3.2)%,和(1.2±0.1)和(1.5±0.1),P<0.05】;在观察期内,两组肾功能指标无显著性变化。结论 应用ADV联合TDF治疗rtA181V/T单位点突变的CHB患者近期效果较好,能够快速抑制病毒复制,稳定肝功能,对肾功能影响较小。     

不同转换治疗策略对经治的低病毒血症慢性乙型肝炎患者疗效的影响:单中心回顾性研究*

目的 探讨不同转换治疗策略对慢性乙型肝炎(CHB)经治发生低病毒血症(LLV)患者疗效 的影响。方法 本研究纳入197例ETV或TDF经治的发生LLV的CHB患者,被分为A组74例,B组63例和C组60例,分别给予ETV或TDF单药维持治疗或TAF替换治疗或ETV或TDF联合长效干扰素(peg-IFN)α-2b治疗观察48周。结果 在48周治疗末,C组完全病毒学应答率(CVR)和HBeAg阴转率分别为90.0%和41.7%,显著高于A组的16.2%和5.4%(P<0.05)或B组的66.7%和9.5%(P<0.05),B组和C组血清ALT复常率分别为20.6%和23.3%,显著高于A组的8.1%(P<0.05);C组血清HBsAg水平为3.0(2.8,3.4)lgIU/ml,显著低于A组【3.3(2.9,3.9)lgIU/ml,P<0.05】或B组【3.4(3.3,3.8)lgIU/ml,P<0.05】,血清HBeAg水平为0.1(-0.7,0.0)lgIU/ml,显著低于A组【0.6(-0.6,1.8) lgIU/ml,P<0.05】或B组【0.6(-0.3,1.8)lgIU/ml,P<0.05】,血清HBV DNA水平为1.3(1.3,1.3)lgIU/ml,显著低于A组【1.7(1.3,2.0)lgIU/ml,P<0.05】或B组【1.6(1.3,1.4)lgIU/ml,P<0.05】;B组和C组肝脏硬度检测(LSM)分别为6.4(4.3,8.4) kPa和6.2(4.2,7.7) kPa,显著低于A组【8.6(5.2,10.7) kPa,P<0.05】,三组血清ALT水平比较,无统计学差异(P＞0.05)。结论 对于核苷类经治出现LLV的CHB患者,为保险起见,换用TAF或继续核苷类联合peg-IFNα-2b治疗可进一步获得较好的病毒学应答率和一定程度的血清学应答率,其对长期疾病转归的影响还需要观察。     

替诺福韦的肾脏-骨骼毒性及其防治

替诺福韦是一种新型核苷酸类逆转录酶抑制剂,用于治疗HIV感染和慢性乙型肝炎。替诺福韦的潜在肾毒性与药物在肾脏排泄有关,病理改变表现为肾小管损害,临床表现为血磷降低和血清肌酸升高,还可导致Fanconi综合征、间质性肾炎和急性肾衰竭。替诺福韦的骨毒性是肾毒性的继发表现,临床表现为肌无力、骨痛和骨折。替诺福韦对肾脏-骨骼损害与基础疾病、基因多态性、血药浓度和药物相互作用有关。服用替诺福韦的患者应定期监测肾功能、电解质,低磷血症患者给予补磷治疗。肌酐清除率﹤50 ml/min的患者应调整替诺福韦的给药剂量。大部分患者在停用替诺福韦后肾功能会明显改善,部分患者可发展为慢性肾病。