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Current trends in the treatment of hepatitis C: interventions to avoid adverse effects and increase effectiveness of anti-HCV drugs

机译:丙型肝炎治疗的当前趋势:为避免不良影响并提高抗丙肝病毒药物的有效性的干预措施

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摘要

Viral hepatitis, an inflammatory liver disease, is caused by various genotypes of hepatitis C viruses (HCV). Hepatitis C slowly sprouts into fibrosis, which progresses to cirrhosis. Over a prolonged period of time compensated cirrhosis can advance to decompensated cirrhosis culminating in hepatic failure and death. Conventional treatment of HCV involves the administration of interferons. However, association of interferon with the adverse drug reactions led to the development of novel anti-HCV drugs given as monotherapy or in combination with the other drugs. Advances in drug delivery systems (DDS) improved the pharmacokinetic profile and stability of drugs, ameliorated tissue damages on extravasation and increased the targeting of affected sites. Liposomes and lipid based vehicles have been employed with polyethylene glycol (PEG) so as to stabilize the formulations as PEG drug complex. Sofosbuvir, a novel anti-HCV drug, is administered as monotherapy or in combination with daclatasvir, ledipasivir, protease inhibitors, ribavirin and interferon for the treatment of HCV genotypes 1, 2 and 3. These drug combinations are highly effective in eradicating the interferon resistance, recurrent HCV infection in liver transplant, concurrent HIV infection and preventing interferon related adverse effects. Further investigations to improve drug targeting and identification of new drug targets are highly warranted due to the rapid emergence of drug resistance in HCV.
机译:病毒性肝炎是一种炎性肝病,由多种基因型丙型肝炎病毒(HCV)引起。丙型肝炎慢慢发芽成纤维化,然后发展为肝硬化。在很长的一段时间内,代偿性肝硬化可发展为代偿性肝硬化,最终导致肝衰竭和死亡。 HCV的常规治疗涉及干扰素的给药。然而,干扰素与药物不良反应的结合导致了新的抗HCV药物作为单一疗法或与其他药物联合使用的发展。药物输送系统(DDS)的进步改善了药物的药代动力学特性和稳定性,改善了外渗时对组织的损害,并增加了对受影响部位的靶向性。脂质体和基于脂质的媒介物已与聚乙二醇(PEG)一起使用,以使制剂稳定为PEG药物复合物。 Sofosbuvir是一种新型抗HCV药物,可以单药治疗,也可以与daclatasvir,ledipasivir,蛋白酶抑制剂,利巴韦林和干扰素联用,用于治疗HCV基因型1、2和3。这些药物组合在消除干扰素耐药性方面非常有效,肝移植中反复出现HCV感染,并发HIV感染和预防干扰素相关的不良反应。由于HCV中耐药性的迅速出现,因此有必要进行进一步的研究以改善药物靶向性并确定新的药物靶标。

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