获得性免疫缺陷综合征患者高效抗逆转录病毒治疗的相关肝毒性

高效抗逆转录病毒治疗(HAART)能有效地抑制HIV复制,并重建机体的免疫功能,大大降低获得性免疫缺陷综合征(AIDS)相关疾病的发病率与病死率.研究表明,HAART治疗后的肝功能损伤已经成为AIDS治疗后的最常见并发症之一,也是患者死亡及中断治疗的重要原因 [1-2].     

高效抗逆转录病毒疗法在艾滋病治疗中的应用进展

目前,高效抗逆转录病毒药物是临床治疗、控制艾滋病最为有效的方法,该类药物自用于艾滋病治疗以来,艾滋病病死率大幅降低,有效改善了艾滋病患者的生活质量,其在艾滋病治疗史上具有里程碑意义。该文就高效抗逆转录病毒药物在艾滋病治疗中的应用进展作一简要综述。     

获得性免疫缺陷综合征抗逆转录病毒治疗的发展和应用

一、研制简史获得性免疫缺陷综合征 (ＡＩＤＳ)抗逆转录病毒的治疗始于 1 986年 ,第 1个核苷类逆转录酶抑制剂齐多夫定 (ＡＺＴ)最初用于临床时 ,对少数患者和人类免疫缺陷病毒 (ＨＩＶ)感染者有明显疗效 ,ＣＤ4淋巴细胞上升 ,病死率明显减少[1] 。但是 ,经过一段时间的应用 ,发现不能有效地阻止ＨＩＶ感染发展成ＡＩＤＳ ,并存在持续的严重不良反应[2 ] 。时隔不久 ,其他核苷类逆转录酶抑制剂如拉米夫定(3ＴＣ)和司他夫定 (ｄ4Ｔ)也相继问世 ,各单剂临床疗效同ＡＺＴ。嗣后 ,与ＡＺＴ同类的另外两个制剂扎西他滨 (ｄｄＣ)和去羟肌苷 (ｄｄ…     

抗逆转录病毒治疗的肝毒性：发生率、发生机制和治疗（上）

应用抗逆转录病毒药物相关的毒性之一就是转氨酶升高。肝毒性是导致HIV感染病人发病、死亡和治疗中断的原因之一．虽然已经报道了几种抗逆转录病毒药物能够引起致命性的急性肝炎，但是大多数的药物最常见的肝毒性是无症状的转氨酶升高。肝毒性更常见于慢性HCV和HBV合并感染的患。对于多数抗逆转录病毒药物而言，药物性肝脏损害的发病率尚不十分清楚。在HAART治疗过程中很难鉴别出每种药物对肝脏的毒性，引起肝毒性的发病机制可能是多方面的，包括直接的药物毒性，合并感染HCV和／或HBV体内的免疫重建，累及肝脏的过敏反应和线粒体毒性。还有其它可能的致病途径，例如几种抗逆转录病毒药物引起的胰岛素抵抗，由此可能会导致脂肺陛肝炎。肝毒性的治疗主要根据临床反应、严重程度和发病机制来进行。     

高效抗逆转录病毒治疗对人类免疫缺陷病毒感染患者骨密度的影响

目的 评价高效抗逆转录病毒治疗(HAART)对HIV感染患者骨密度(BMD)的影响及其相关因素.方法 收集2007-2008年间50例接受HAART的HIV/MDS患者(治疗组)、12例未用HAART的HIV/AIDS患者(未治疗组)、20例健康对照者(对照组)的临床资料,采用双能X线BMD吸收仪(DEXA)测定BMD以及T值,分别对其数据进行统计分析.结果 治疗组中19例(38.0%)患者发生骨量减少,1例(2.0%)患者发生骨质疏松.对照组中5例(25.0%)发生骨量减少,无骨质疏松者.未治疗组中6例(50.0%)患者发生骨量减少,2例(16.7%)患者发生骨质疏松.未治疗组骨量减少/骨质疏松发生率较对照组显著增高(P=0.02).HIV/AIDS组(包括未治疗组和治疗组)的股骨、股骨颈、大粗隆的BMD[(0.97±0.14)、(0.91±0.13)、(0.76 4-0.12)g/cm2]明显低于对照组[(1.04±0.12)、(0.98±0.14)、(0.84±0.11)g/cm2,P<0.05];而未治疗组和治疗组的BMD差异无统计学意义.治疗组中,骨量减少/骨质疏松与体重<60 kg(r=0.074,P=0.004)、使用HAART前血浆病毒载量(r=5.103,P=0.021)呈正相关.结论 未接受HAART的HIV/AIDS患者较健康人骨量减少/骨质疏松发生率高.HIV/MDS患者BMD较健康人低,接受HAART和未接受HAART治疗的HIV/AIDS患者BMD相当.接受HAART患者中,体重<60 kg、治疗前HIV RNA是发生骨量减少/骨质疏松的危险因素.     

高效抗逆转录病毒治疗12个月后艾滋病患者的免疫重建观察

目的探讨高效抗逆转录病毒治疗（HAART）对AIDS患者的疗效及毒副作用。方法45例未经治疗的AIDS病人按基线CD4^＋T细胞计数分为两组,予12个月HAART,分别在基线及治疗1、3、6、9、12个月末随访血浆病毒载量（VL）、T细胞亚群和临床症状。结果抗病毒治疗12个月后45例病人血浆VL平均下降2．8lg拷贝／ml;CD4^＋细胞平均增长187个／μl,其中记忆表型增长119个／μl,纯真表型增长68个／μl,CD4^＋CD28^＋细胞比例显著升高;CD8^＋T激活亚群比例显著降低。基线CD4^＋T细胞计数〉100个／μl的14例病人治疗12个月后有10例血浆VL〈50拷贝／ml,而〈100个／μl的31例病人治疗后仅有11例血浆VL〈50拷贝／ml（P〈0．05）。出现血浆波动的病例数在两组也有统计学差异（分别为2例和14例,P〈0．05）。CD4^＋T细胞计数呈双相增长过程,其增量与血浆VL减少量呈显著正相关。常见的药物副作用有消化道反应、外周神经炎、肝功能损害等。结论HAART方案对AIDS病人有较好的疗效,能够实现免疫重建,但也存在较多毒副作用。     

天津市高效抗逆转录病毒治疗艾滋病临床观察

目的评价天津市艾滋病（AIDS）初治患者,应用高效抗逆转录病毒治疗（HAART）的疗效、安全性和预后。方法将在天津市传染病医院就诊的62例AIDS患者,随机分成治疗组（45例）及对照组（17例）;治疗组应用一线HAART方案：AZT／D4T＋3TC＋NVP／EFV。观察两组患者的临床表现、免疫功能变化及预后。结果（1）HAART治疗组与对照组患者基线CD4 T细胞计数差异无统计学意义（P〉0．5）;治疗组的45例患者,HAART前CD4 T细胞计数均值为73／μl;HAART后3、6、12个月时分别为120／μl（39例）、139．5／μl（30例）和200／μl（22例）。（2）治疗组患者应用HAART后,机会性感染、肿瘤的发生率和病死率分别为40％和4．44％,均显著低于对照组的88．24％和47．06％（P〈0．01）。（3）初治患者一线HAART治疗的有效率为95．55%（43／45）,有17．78％（8／45）的患者因药物不良反应而调整HAART方案。结论天津市AIDS患者对一线HAART有较好的疗效,随着HAART疗程的延长,免疫功能得到恢复并改善了预后,存在药物不良反应和资源有限等问题。     

尽早启动抗逆转录病毒治疗可以降低药物的毒性

研究人员近期在《获得性免疫缺陷综合征》上报告，在HIV感染者的CD4^＋T细胞计数高于200个细胞／微升时便启动抗逆转录病毒治疗可以降低患者外周神经疾病、贫血和肾功能不全的发病率。     

Clinical and histologic features of Azathioprine-induced hepatotoxicity

Background: Hepatoxicity is a relative uncommon complication related with Azathioprine, however most studies were performed in inflammatory bowel diseases patients. The aim of this study is to report the clinical profile of patients with Azathioprine-induced hepatotoxicity.

Methods: All medical records of patients received Azathioprine from 2010 to 2015 were retrospectively reviewed. Hepatotoxicity was defined as serum alanine aminotransferase (ALT) or aspatate aminotransferase (AST) or total bilirubin >2 times upper limit normal. Other causes of liver diseases were excluded. All subjects were followed until the resolution of liver injury.

Results: Two-hundred and ninety-three patients receiving Azathioprine were retrospectively reviewed. Eight patients (2.7%) were diagnosed with Azathioprine-induced hepatotoxicity. The median age was 45 year with female preponderance. The latency to onset of liver injury ranged from 7 to 236 d, and 4 patients were symptomatic. Median peak levels were ALT 295?U/L, alkaline phosphatase 169?U/L, and total bilirubin 1?mg/dl. According to R-ratio, mixed pattern (50%) was more frequent than cholestatic (37.5%) and hepatocellular pattern (12.5%). Liver biopsies were performed in 2 patients, and showed hepatocellular and canalicular cholestasis with mild portal and peri-portal inflammation. All patients recovered fully with a median time of 41.3 days. Two patients developed prolonged cholestasis >2 months, hence none had liver failure or required liver transplantation.

Conclusion: Hepatotoxicity is relative uncommon in patients receiving Azathioprine, and predominantly is mixed hepatocellular and cholestatic in nature. Even though all patients recover fully after drug withdrawal, severe cholestasis can occur.     

Distinct and convergent consequences of splice factor mutations in myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are characterized by recurrent somatic alterations often affecting components of RNA splicing machinery. Mutations of splice factors SF3B1, SRSF2, ZRSR2 and U2AF1 occur in >50% of MDS. To assess the impact of spliceosome mutations on splicing and to identify common pathways/genes affected by distinct mutations, we performed RNA-sequencing of MDS bone marrow samples harboring spliceosome mutations (including hotspot alterations of SF3B1, SRSF2 and U2AF1; small deletions of SRSF2 and truncating mutations of ZRSR2), and devoid of other common co-occurring mutations. We uncover the landscape of splicing alterations in each splice factor mutant MDS and demonstrate that small deletions in SRSF2 cause highest number of splicing alterations compared with other spliceosome mutations. Although the mis-spliced events observed in different splice factor mutations were largely non-overlapping, a subset of genes, including EZH2, were aberrantly spliced in multiple mutant groups. We also verified aberrant splicing of key genes USP9X, USP24 (deubiquitinating enzymes), LUC7L2 (splice factor) and EED (PRC2 component) in MDS harboring small deletions of SRSF2. Pathway analysis revealed that mis-spliced genes in different mutant groups were enriched in RNA splicing and transport as well as several signaling cascades, suggesting converging biological consequences downstream of distinct spliceosome mutations. Our study reveals splicing signatures of each splice factor mutation and identifies shared and distinct sets of mis-spliced genes and affected biological processes in different spliceosome mutant MDS.     

心肾综合征的临床进展

心脏或肾脏中任一器官急性或慢性功能障碍时,另一器官继发急性或慢性病变的临床综合征称为心肾综合征(CRS)。根据心肾疾病发生的机制和时间顺序,可将CRS分为5种亚型。CRS的新定义和分型方法的出现,使临床医生对于其理解更加清晰。     

Clinical consequences of antiphospholipid antibodies

Antiphospholipid antibodies (aPL), notably the lupus anticoagulant and anticardiolipin antibodies, are the serological hallmarks of the antiphospholipid syndrome. Thrombosis and pregnancy complications are the most prominent clinical manifestations of this syndrome. This paper provides the clinician with guidelines for ordering and interpreting tests for aPL and discusses consequences for treatment if persistently positive tests are found.