Therapy of hepatitis C: Other options
Therapy of hepatitis C: Other options
复制标题
DOI：
10.1002/hep.510260725
复制
发表时间：
1997-09-01
期刊：
影响因子：
13.5
通讯作者：
Bonkovsky, HL
中科院分区：
文献类型：
--
作者：
Bonkovsky, HL
由于目前使用α干扰素治疗慢性丙型肝炎的标准疗法不太理想，许多其他方法已经被研究。肝脏中的铁，特别是在门静脉血管内皮细胞中发现的铁，与对α干扰素治疗的反应性降低有关。单纯的铁减少，通常是通过治疗性静脉切开实现的，通常与生化改善(血清丙氨酸氨基转移酶降低)有关，但与病毒学改善无关。据报道，减少铁含量可以增加对α干扰素的治疗反应。这种组合的大多数研究都是在没有单独对干扰素有反应的患者身上进行的；在这些患者中，在一些研究中观察到了改善的反应性，但不是所有的研究。在以前没有接受治疗的患者中，最近的一项试验发现，减少铁可以将持续的生化和病毒学应答率从5%提高到29%。肝脏铁和慢性丙型肝炎会增加肝脏中的氧化应激，并与肝脏谷胱甘肽水平的下降有关。在一份报告中，给予巯基供体N-乙酰半胱氨酸可以改善慢性丙型肝炎患者对干扰素的反应。几种细胞因子和免疫调节剂的研究有限；其中最有希望的可能是胸腺素α-1。在一项小型研究中，金刚烷胺被发现对以前对干扰素无效的患者产生了一些反应。乌索二醇可改善慢性丙型肝炎患者的血清转氨酶水平，但没有抗病毒作用，也没有发现它能改善组织学异常。慢性丙型肝炎的未来治疗可能包括减少氧化应激和损伤的措施，以及多种药物的组合，包括丙型肝炎病毒蛋白酶和RNA聚合酶的抑制剂。
Because current standard therapy of chronic hepatitis C with alpha interferon is less than ideal, numerous other approaches have been studied. Iron in the liver, particularly that found in vascular endothelial cells of portal tracts, has been associated with decreased responsiveness to alpha interferon therapy. Iron reduction alone, generally achieved by therapeutic phlebotomy, regularly has been associated with biochemical improvement (decrease in serum alanine aminotransferase), but not with virology improvement. Iron reduction has been reported to increase the therapeutic response to alpha interferon. Most studies of this combination have been conducted in patients who had not responded to interferon alone; in these patients, improved responsiveness has been observed in some, but not all studies. In patients not previously treated, iron reduction was found in a recent trial to improve the sustained biochemical and virological response rate from 5% to 29%. Hepatic iron and chronic hepatitis C increase oxidative stress in the liver and are associated with decreases in hepatic glutathione levels. In one report, administration of N-acetyl cysteine, a sulfhydryl donor, led to improved response to interferon in chronic hepatitis C. Several cytokines and immunomodulators have undergone limited study; perhaps the most promising of these is thymosin alpha-1. In one small study, amantadine was found to produce some response in patients who previously had failed to respond to interferon. Ursodiol improves serum aminotransferase levels in chronic hepatitis C but has no antiviral effect, nor has it been found to improve histologic abnormalities. The future of therapy of chronic hepatitis C will likely include measures to decrease oxidative stress and injury and multidrug combinations, including inhibitors of the hepatitis C viral protease and RNA polymerase.