Novel delivery methods for treatment of viral hepatitis: an update

Viral hepatitis represents the most common cause of chronic liver disease worldwide. Currently approved therapies for chronic hepatitis B include IFN, an immune modulator, and nucleoside analogues lamivudine and adefovir. For chronic hepatitis C, a combination of pegylated IFN-alpha and ribavirin represents the standard treatment. However, currently available treatments for both these viruses are effective only in a limited number of patients, are costly, prolonged, associated with significant side effects and require a substantial commitment from the patients and healthcare providers. A number of novel antiviral treatments, together with strategies to enhance the response to current therapies, are being explored at present. For all new therapies, as well as for improving existing treatments, selective delivery of medications into liver cells would be desirable to enhance antiviral activity and avoid systemic side effects. New achievements in the field of drug and gene delivery against chronic hepatitis to the liver are reviewed here.     

Polymers for viral gene delivery

Background: The development of viral vectors capable of providing efficient gene transfer in diseased tissues without causing any pathogenic effects is pivotal for overcoming the many challenges facing gene therapy. Objective: Immune responses against viral vectors, inadequate gene expression and inefficient targeting to specific cells in vivo are some of the major problems limiting the clinical utility of viral gene therapy. Methods: This review will focus on recent progress in strategic polymer-based modifications to improve the performance and biocompatibility of a variety of viral vectors. We will discuss the preclinical development of four approaches involving injectable polymers, polyelectrolytes, polymer microspheres and polymer–virus conjugates. Results/conclusion: Much progress has been made in creating ‘hybrid’ gene delivery vectors that combine the strengths of polymers and viruses. With further optimization, these hybrid vectors, which may be safer and more effective, are likely to succeed in clinical applications.     

复方卡尼汀治疗慢性病毒性肝炎

目的 :评估复方卡尼汀治疗慢性病毒性肝炎的作用。方法 :91例慢性病毒性肝炎病人分为 2组。对照组 30例 (男性 2 0例 ,女性 10例 ,年龄 4 1a±s 17a) ,给予甘草酸单铵 80mL加入 10 %葡萄糖注射液 50 0mL中iv ,gtt ,qd ,疗程 30d。治疗组61例 (男性 4 9例 ,女性 12例 ,年龄 4 0a± 13a) ,在甘草酸单铵治疗基础上 ,给予复方卡尼汀 2支加入10 %葡萄糖注射液 50 0mL中iv ,gtt ,qd ,疗程 30d。结果 :治疗组对改善病人乏力、纳差、降低ALT的总有效率分别为 93% ,10 0 % ,92 % ,均明显优于对照组 75% ,84 % ,70 % (P <0 .0 5)。对 2组部分病人治疗 6mo时的随访表明治疗组的ALT复常率为83% ,明显高于对照组 54% (P <0 .0 5) ,无明显不良反应。结论 :复方卡尼汀是一种有效的治疗慢性病毒性肝炎的药物     

谷胱甘肽辅助治疗重型病毒性肝炎和肝炎肝硬化

目的：探讨谷胱甘肽辅助治疗重型病毒性肝炎和肝炎肝硬化的疗效。方法：４０例病人分成２组，治疗组２０例（男性１６例，女性４例；年龄４４±ｓ１１ａ）在综合性治疗（用甘草酸二铵、肝细胞生长因子、茵栀黄等）基础上用谷胱甘肽０．６～１．２ｇ加入１０％葡萄糖注射液２５０ｍＬ中静脉滴注，ｑｄ，连续１～２ｍｏ。对照组２０例（男性１８例，女性２例；年龄４６±１２ａ）单用综合治疗。结果：治疗组症状、体征改善明显优于对照组（Ｐ＜０．０１，Ｐ＜０．０５）。总胆红素、凝血酶原时间变化亦优于对照组（Ｐ＜０．０５），但丙氨酸转氨酶治疗后２组间无明显差别（Ｐ＞０．０５）。结论：谷胱甘肽辅助治疗病毒性肝炎及肝炎肝硬化有较好的疗效。     

肝宁片联合异甘草酸镁治疗慢性病毒性肝炎的临床研究

目的探讨肝宁片联合异甘草酸镁注射液治疗慢性病毒性肝炎的临床疗效。方法选取2016年5月—2017年5月在南阳市第二人民医院进行治疗的慢性病毒性肝炎患者88例为研究对象,根据用药的不同将患者分为对照组和治疗组,每组各44例。对照组静脉滴注异甘草酸镁注射液,150 mg加入到5%葡萄糖注射液250 m L中,1次/d。治疗组在对照组基础上口服肝宁片,0.9 g/次,3次/d。两组患者均治疗4周。观察两组的临床疗效,比较两组的肝纤维化指标、肝功能指标和血清学指标。结果治疗后,对照组和治疗组的总有效率分别为81.82%、95.45%,两组比较差异有统计学意义(P0.05)。治疗后,两组血清透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(Ⅳ-C)水平均显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组肝纤维化指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清ALT、AST、TBIL水平均明显降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组肝功能指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清转化生长因子-β_1(TGF-β_1)、巨噬细胞移动抑制因子(MIF)、白细胞介素-18(IL-18)、基质金属蛋白酶-13(MMP-13)水平均显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组血清学指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。结论肝宁片联合异甘草酸镁注射液治疗慢性病毒性肝炎具有较好的临床疗效,可改善患者肝功能和肝纤维化指标,调节血清TGF-β_1、MIF、IL-18和MMP-13水平,具有一定的临床推广应用价值。     

复方卡尼汀注射液治疗病毒性肝炎

目的 :观察复方卡尼汀注射液治疗病毒性肝炎的疗效。方法 :对照组 30例 ,男性 2 4例 ,女性 6例 ,年龄 ( 41±s 11)a ,常规保肝治疗 (菌栀黄 2 0mL ,iv ,gtt ,qd ,维生素C 2 .0g及维生素B60 .2g ,iv ,gtt ,qd等 ) ,疗程 4wk。治疗组 30例 ,男性2 4例 ,女性 6例 ,年龄 ( 45± 10 )a ,常规保肝治疗加用复方卡尼汀注射液 2支 ,iv ,gtt ,qd ,疗程 4wk。结果 :2组临床疗效比较差别有显著意义 (P<0 .0 5 ) ;2组丙氨酸转氨酶 (ALT)治疗前后比较差别均有显著意义 (P <0 .0 5 ) ,血清总胆红素 (TB)治疗前后比较 ,治疗组差别有显著意义 (P <0 .0 5 ) ,对照组差别无显著意义 (P >0 .0 5 ) ;治疗后 2组组间比较ALT差别无显著意义 (P >0 .0 5 ) ,TB差别有非常显著意义 (P <0 .0 1)。 2组均无明显副作用。结论 :复方卡尼汀注射液是一种有效安全的保肝药 ,尤以降低TB作用更佳     

促肝细胞生长素肠溶胶囊治疗慢性乙型病毒性肝炎72例疗效观察

目的观察促肝细胞生长素肠溶胶囊治疗慢性乙型病毒性肝炎的疗效。方法144例患者随机分为两组,72例常规治疗加促肝细胞生长素肠溶胶囊作为试验组,每日服2粒,每日3次,疗程12周;另72例常规治疗加促肝细胞生长素颗粒剂作为对照组,每次2袋,每日3次,疗程12周。服药前及服药时4、8、12周及治疗结束后4、8、12周测定肝功能、症状与体征变化。结果两组治疗后肝功能的多项指标均有明显改善,且治疗结束后12周肝功能尚持续改善;临床症状和体征也有明显改善,治疗组总有效率达76.57%。结论促肝细胞生长素肠溶胶囊能有效改善慢性乙型病毒性肝炎患者症状、体征与肝功能,且未见明显不良反应,使用安全。     

双环醇片治疗2200例慢性病毒性肝炎的安全性和疗效分析

目的:通过Ⅳ期临床试验评估双环醇片治疗慢性乙型肝炎和慢性丙型肝炎的安全性和疗效。方法:随机选择12～65a的2200例慢性乙型肝炎和慢性丙型肝炎病人接受治疗,每日口服双环醇片75mg,观察连续用药24wk(近期)及停药12wk后(远期)的安全性和疗效,以血清丙氨酸转氨酶(ALT)作为主要疗效评估指标。结果:试验过程中未发生严重不良事件,不良事件发生率为10.87%。意向性分析(ITT)统计显示,慢性乙型肝炎和慢性丙型肝炎病人治疗24wk末的ALT复常率分别为60.37%和54.0%,停药12wk后的ALT持续复常率分别为71.88%和65%。结论:双环醇片75mg·d-1治疗慢性乙型肝炎和慢性丙型肝炎安全,对改善肝功能有效。     

Efavirenz concentrations in HIV-infected patients with and without viral hepatitis

AIMS

Data on efavirenz in HIV/viral hepatitis co-infected patients is non-consensual, probably due to liver function heterogeneity in the patients included.

METHODS

A case control study was performed on 27 HIV-infected patients, with controlled and homogenous markers of hepatic function, either mono-infected or co-infected with HBV/HCV, to ascertain the influence of viral hepatitis on efavirenz concentrations over a 2-year follow-up period.

RESULTS

No differences were found in efavirenz concentrations between groups both during and at the end of the follow-up period: control (2.43 ± 1.91 mg l^–1) vs. co-infected individuals (2.37 ± 0.37 mg l^–1).

CONCLUSION

It was concluded that HBV/HCV infections in themselves do not predispose to an overexposure to efavirenz.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• HIV-1 co-infection with HBV/HCV is the most important factor determining efavirenz-induced liver toxicity. Higher efavirenz plasma concentrations have been reported in these patients facilitating concentration drug-related adverse effects.
• It is not known whether changes in efavirenz disposition are due to the hepatitis infection/inflammation or to liver failure. As a consequence, the guidelines for the application of therapeutic drug monitoring of efavirenz in HBV/HCV co-infected patients have not been established.

WHAT THIS STUDY ADDS

• The present study has shown that HBV/HCV infection in itself does not predispose to higher efavirenz plasma concentrations. In the absence of hepatic failure, the risk of efavirenz concentration-dependent toxicity is not increased.
• Thus, therapeutic drug monitoring indications in co-infected patients with hepatic function within the normal range should be the same as in HIV-1 mono-infected patients.

     

胸腺肽α_1在慢性病毒性肝炎抗病毒治疗中的应用

胸腺肽α1是从胸腺素第5组分中分离纯化出的一种小分子生物活性多肽。近年来,胸腺肽α1开始用于慢性乙型病毒性肝炎和慢性丙型病毒性肝炎的治疗,其耐受性较好,可能成为一种较好的治疗药物。但是,由于胸腺肽α1治疗肝炎相关数据的缺乏,使得人们对其治疗作用及作用机制还不太明确。鉴于此,本文对胸腺肽α1在病毒性肝炎抗病毒治疗中的应用进行综述。     

脉络宁对重型肝炎患者血小板活性的影响

目的：探讨脉络宁对重型肝炎患者血小板活性的影响。方法：采用ＥＬＩＳＡ法和单克隆酶联免疫吸附法。检测了５１例慢性重型肝炎患者和４４例健康体检者的血浆内血小板α颗粒膜蛋白（ＧＭＰ－１４０）和血管性假血友病因子相关抗原（ｖＷＦ：Ａｇ）含量。５１例慢性重型肝炎患者血浆ＧＭＰ－１４０、ｖＷＦ：Ａｇ含量均明显高于正常对照组（Ｐ〈０．０１）。脉络宁治疗组用药两周后,脉络宁对该病患者的血小板活性具有明显抑制作用。     

肝康宁片联合替诺福韦治疗病毒性肝炎的临床研究

目的探讨肝康宁联合替诺福韦治疗病毒性肝炎的临床疗效。方法选取2017年5月—2018年5月在荆州市第二人民医院治疗的病毒性肝炎患者84例,根据就诊号分为对照组(42例)和治疗组(42例)。对照组口服富马酸替诺福韦二吡呋酯片,300 mg/次,1次/d;治疗组在对照组基础上口服肝康宁片,5 g/次,3次/d。两组患者均连续治疗12周。观察两组患者临床疗效,同时比较治疗前后两组患者肝功能、肝纤维化和细胞因子水平。结果治疗后,对照组和治疗组临床有效率分别为80.95%和97.62%,两组比较差异具有统计学意义(P0.05)。治疗后,两组丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)、总胆汁酸(TBA)、白细胞介素-18(IL-18)、降钙素原(PCT)、巨噬细胞移动抑制因子(MIF)、肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶-13(MMP-13)、透明质酸(HA)、Ⅲ型前胶原N端肽(PC-Ⅲ)、Ⅳ型胶原(Ⅳ-C)、层黏连蛋白(LN)水平明显降低,同组比较差异具有统计学意义(P0.05),且治疗组患者上述指标水平明显低于对照组,两组比较差异具有统计学意义(P0.05)。结论肝康宁联合替诺福韦治疗病毒性肝炎不仅可以改善患者肝功能和肝纤维化,还可以降低机体炎性反应、增加机体免疫力。     

还原性谷胱甘肽对病毒性肝炎的疗效观察

目的:观察还原性谷胱甘肽(GSH)对病毒性肝炎的疗效。方法:106例病毒性肝炎患者随机分为A组(治疗组)、B组(对照组),分别用GSH和门冬氨酸钾镁治疗,疗程均为4周。结果:GSH对治疗急、慢性病毒性肝炎的乏力有效率分别为94.4%(17/18)、88.7%(31/35),对钠差的有效率分别为88.9%(16/18)、85.7%(30/35),与对照组比较有显著性差异(P<0.05)。治疗组急、慢性肝炎患者的血清总胆红素(STB)、血清结合胆红素(SCB)、总胆汁酸(TBA)、血清谷丙转氨酶(ALT)、血清谷草转氨酶(AST)的降幅明显高于对照组(P<0.05),慢性肝炎的白蛋白(ALB)在治疗后增高也有显著性差异(P<0.05),ALT、AST的复常率也显著高于对照组(P<0.05)。结论:GSH对病毒性肝炎的疗效较好,优于门冬氨酸钾镁。     

Microneedle-mediated delivery of viral vectored vaccines

Introduction: Microneedle array platforms are a promising technology for vaccine delivery, due to their ease of administration with no sharp waste generated, small size, possibility of targeted delivery to the specified skin depth and efficacious delivery of different vaccine formulations, including viral vectors.

Areas covered: Attributes and challenges of the most promising viral vector candidates that have advanced to the clinic and that have been leveraged for skin delivery by microneedles; The importance of understanding the immunobiology of antigen-presenting cells in the skin, in particular dendritic cells, in order to generate further improved skin vaccination strategies; recent studies where viral vectors expressing various antigens have been coupled with microneedle technology to examine their potential for improved vaccination.

Expert opinion: Simple, economic and efficacious vaccine delivery methods are needed to improve health outcomes and manage possible outbreaks of new emerging viruses. Understanding what innate/inflammatory signals are required to induce both immediate and long-term responses remains a major hurdle in the development of the effective vaccines. One approach to meet these needs is microneedle-mediated viral vector vaccination. In order for this technology to fulfil this potential the industry must invest significantly to further develop its design, production, biosafety, delivery and large-scale manufacturing.     

Patent focus on drug delivery: June - November 1999

The article highlights the most recent disclosures in the field of drug formulation and delivery for the period June - November 1999. The limited number of patents published in this period in the field of drug delivery focus on the delivery of the newer biopharmaceuticals such as genes and vaccines. In addition patents on novel vectors for drug delivery are highlighted - these concentrate on biological-based systems rather than polymeric systems which have been of particular interest over recent years.     

Gene delivery strategies for the treatment of mucopolysaccharidoses

Introduction: Mucopolysaccharidosis (MPS) disorders are genetic diseases caused by deficiencies in the lysosomal enzymes responsible for the degradation of glycosaminoglycans. Current treatments are not able to correct all disease symptoms and are not available for all MPS types, which makes gene therapy especially relevant. Multiple gene therapy approaches have been tested for different types of MPS, and our aim in this study is to critically analyze each of them.

Areas covered: In this review, we have included the major studies that describe the use of adeno-associated retroviral and lentiviral vectors, as well as relevant non-viral approaches for MPS disorders.

Expert opinion: Some protocols such as the use of adeno-associated vectors and lentiviral vectors are approaching the clinic for these disorders and, along with combined approaches, seem to be the future of gene therapy for MPS.     

118例病原学指标阴性的肝病患者病因临床分析

目的了解肝炎病毒血清学标志阴性的肝病患者的病因。方法选择甲、乙、丙、丁、戊型病毒性肝炎血清学标志阴性的患者118例。对临床上诊断为病原学阴性的肝病患者血清,分别进行自身免疫性肝病抗体,ANA全套,FT3、VF4及TSH,血清Cu及铜蓝蛋白的检测。收集临床资料,分析结果。结果118例肝炎病毒血清学标志阴性的肝病患者中47例是病因不明的肝病,在病因不明的47例肝病患者中,14例患者的血清ANA等自身抗体中至少一种抗体为阳性。结论对病因不明的肝病有必要检测自身抗体,以排除自身免疫性肝病。     

硫普罗宁治疗儿童急性甲型肝炎疗效观察

目的:评估硫普罗宁治疗儿童甲型肝炎的临床疗效。方法:随机分成治疗组和对照组,治疗组在对照组常规保肝降酶治疗的基础上加用硫普罗宁100mg静脉滴注,1次/d,连用7d后复查肝功能及观察症状、体征变化。结果:治疗组在症状、体征特别是退黄疸和降低转氨酶方面明显优于对照组(P<0.05)。结论:硫普罗宁治疗儿童甲型肝炎有良好疗效。     

慢性病毒性肝炎伴糖代谢紊乱患者药学监护的分析

摘要 慢性病毒性肝炎尤其伴肝硬化时,常出现糖代谢紊乱,病情十分复杂,治疗中需要解决的药学问题有很多。本文以降糖药物、保肝药物及抗菌药物使用监护为切入点,结合我院临床药师参与药学监护的3例典型病例,提出慢性病毒性肝炎伴糖代谢紊乱药学监护要点为：降血糖药物应避免使用损害肝功能的口服降糖药物,尽量选用胰岛素;保肝药物应避免使用可能升高血糖的甘草酸制剂等药物;抗菌药物使用时应避免使用对肝功能有损害及对血糖有影响的抗菌药物。实施这些药学监护,对慢性病毒性肝炎伴糖代谢紊乱患者血糖控制、肝功能恢复等均有重要临床意义。     

拉米夫定治疗乙型肝炎的抗病毒疗效和耐药性

拉米夫定是第1个正式进入临床治疗慢性乙型肝炎病毒(HBV)感染的口服核苷类药物。现对拉米夫定治疗乙型肝炎病毒感染的作用特点、临床应用、病毒变异以及对疗效的影响进行综述。