Friedlander L, van Thiel D H, Faruki H, Molloy P J, Kania R J, Hassanein T
West Penn Hospital, Pittsburgh 15224, USA.
Dig Dis Sci. 1996 Aug;41(8):1678-81. doi: 10.1007/BF02087924.
Chronic viral hepatitis C is a problem of immense proportions. The only therapy that currently exists and is FDA approved is interferon (IFN). Much controversy exists regarding the dose and duration as well as the effectiveness of IFN therapy. This study was performed to determine whether a new endpoint of successful treatment, HCV-RNA negativity in plasma and liver, would produce a greater number of long-term responders than is achievable with the currently recommended six months of therapy. The 45 patients enrolled in this study were randomized 2 to 1 in a treatment paradigm consisting of 5 MU IFN three times a week for six months or the same dose of IFN daily until HCV-RNA was undetectable in plasma X 3 over 3 consecutive monthly determinations followed by demonstrated HCV-RNA negativity in liver biopsy tissue. No differences in age, initial WBC count, platelet count, or hepatic injury measures were evident between the two treatment groups. At the end of therapy, 43% of those in group 1 vs 100% in group 2 responded to the IFN therapy as defined by the serum ALT level. More importantly, all of those in group 1, but only half of those in group 2, relapsed and became HCV-RNA positive with discontinuation of the IFN therapy. These data suggest that: (1) IFN therapy is more effective when given for a longer rather than a shorter period; (2) virologic response definitions are now possible and are preferred; (3) using longer therapy and a virologic endpoint, the responses achieved are more durable.
慢性丙型病毒性肝炎是一个极为严重的问题。目前唯一存在且获美国食品药品监督管理局（FDA）批准的治疗方法是干扰素（IFN）。关于干扰素治疗的剂量、疗程以及疗效存在诸多争议。本研究旨在确定一个成功治疗的新终点，即血浆和肝脏中丙型肝炎病毒核糖核酸（HCV - RNA）呈阴性，是否会比目前推荐的六个月疗程产生更多的长期缓解者。本研究纳入的45例患者按2比1随机分组，治疗方案为：一组每周三次，每次5百万单位（MU）干扰素，持续六个月；另一组每日给予相同剂量的干扰素，直至连续三个月每月测定血浆中HCV - RNA均检测不到，随后肝活检组织中HCV - RNA也呈阴性。两个治疗组在年龄、初始白细胞计数、血小板计数或肝损伤指标方面均无明显差异。治疗结束时，根据血清谷丙转氨酶（ALT）水平定义，第1组中43%的患者对干扰素治疗有反应，而第2组为100%。更重要的是，第1组所有患者在干扰素治疗中断后均复发并再次变为HCV - RNA阳性，而第2组只有一半患者如此。这些数据表明：（1）干扰素治疗疗程较长时比疗程较短时更有效；（2）现在可以采用病毒学反应定义，且更受青睐；（3）采用更长疗程和病毒学终点，所取得的反应更持久。
