Marcellin P, Asselah T, Ripault M P, Boyer N
Unit of Hepatology, Claude Bernard Research Center on Viral Hepatitis, INSERM U-481, Hospital Beaujon, Clichy, France.
Minerva Gastroenterol Dietol. 2004 Mar;50(1):29-36.
Since the discovering of the hepatitis C virus in 1989, the treatment of hepatitis C has considerably improved. Initially, with interferon alpha used as a single drug, the sustained virological response rate was below 20%. Then, with the use of combination therapy of interferon a with ribavirin, the response rate increased to 41%. More recently, combination of pegylated interferons with ribavirin give a response rate of about 54-63%. The long-term follow-up studies showed that sustained virological response is generally associated with clinical and histological improvement. The indication of therapy is mainly based on the results of the liver biopsy which is the best way to assess the prognosis of the liver disease. Therefore, treatment is indicated in patients with moderate or severe necroinflammation or fibrosis. The tolerability of combination therapy is relatively poor with a frequent flu-like syndrome and an impaired quality of life. Factors associated with a poor response to treatment are essentially genotype 1 and high viral load. To further improve the efficacy of therapy, different new drugs are under investigation (amantadine, cytokines). These drugs may be candidates for new combinations. In addition, intensive research is currently done for the development of inhibitors of viral enzymes (helicase, protease or polymerase) and anti-sense oligonucleotides, ribozymes and therapeutic vaccine.
自1989年丙型肝炎病毒被发现以来，丙型肝炎的治疗有了显著改善。最初，使用单一药物α干扰素时，持续病毒学应答率低于20%。随后，使用α干扰素与利巴韦林的联合疗法，应答率提高到了41%。最近，聚乙二醇化干扰素与利巴韦林联合使用的应答率约为54% - 63%。长期随访研究表明，持续病毒学应答通常与临床和组织学改善相关。治疗指征主要基于肝活检结果，这是评估肝病预后的最佳方法。因此，对于中度或重度坏死性炎症或纤维化患者应进行治疗。联合疗法的耐受性相对较差，常伴有类似流感的综合征，生活质量受损。与治疗反应不佳相关的因素主要是基因1型和高病毒载量。为进一步提高治疗效果，不同的新药正在研究中（金刚烷胺、细胞因子）。这些药物可能成为新联合用药的候选药物。此外，目前正在深入研究开发病毒酶抑制剂（解旋酶、蛋白酶或聚合酶）以及反义寡核苷酸、核酶和治疗性疫苗。
