第24届亚太地区肝脏研究协会年会（APASL）于2014年3月12～15日在澳大利亚布里斯班召开。会议上展示了名为“孤星试验”的结果。所谓“孤星试验”即给100个丙肝患者每日服用单次固定剂量的sofosbuvir (SOF)与 ledipasvir (LDV)的合用剂，来检测在处方中加入利巴韦林（RBV）的必要性。试验结果显示无论是否加入 RBV，都会产生97%的持久病毒应答（SVR）。
之前的研究已经证实了12周固定剂量的SOF与LDV合用剂（以下简称合用剂），与RBV同时使用时，对于首次接受该项治疗的患者和无效应答的患者都有很好的疗效。承担该项研究的专家，美国德克萨斯肝病协会的Erick Lawitz及其同事想通过相同的试验进一步检测是否RBV和治疗时间对于高的持久病毒应答起到了重要作用。
即将60个首次接受该治疗的患者平均随机分配到下列三组不同治疗方案中的一组：1）使用合用剂8周，2）使用合用剂+RBV 8周，3）使用合用剂12周。同时，另外40位无效应答的病人被分为2组：1）合用剂，2）合用剂+RBV。所有的病人均为HCV基因型1。没有发现严重的不良反应事件，并且轻微的不良反应与之前的研究相一致。
研究者们已经证实了第二代抗病毒药物的有效性，即可以通过12周的治疗消除HCV。与此同时，还需要长期的研究来证实该结论。
专家点评
Amanda Nicoll
墨尔本皇家医院的胃肠病与肝病副院长Amanda Nicoll针对孤星试验作出详细说明，该项研究检验了在不使用干扰素的情况下，用SOF（即尿嘧啶核苷类似物）和LDV（NS5A抑制剂）治疗基因型1的丙肝病毒患者的治疗效果。在该项研究中，所治疗的病人包括了之前接受蛋白酶抑制剂（n=40）的病人，以及没有接受过蛋白酶抑制剂（n=60）的病人。大部分病人的基因型为1a,80%的病人为IL28B-非 CC。接受治疗后的12周的持久病毒应答为95-100%。只发现了轻微的不良反应并且只有一个病人提前放弃治疗。
Amanda Nicoll还表示，未来的丙肝治疗似乎要比想象的容易一些。仅使用两种药物的短期治疗（8-12周）可在肝脏硬化、无效应答以及非有利IL28B基因型患者中引起持续的病毒学应答。不可避免的是将有一小部分病人对此处方无效，并且需要长期治疗或更多的药物，但这种情况的概率是很低的。
原文阅读：The Lonestar Trial: SOF/LDV Combination Sufficient for SVR12 without RBV
The results of the Lonestar Trial are set to be presented at this year’s APASL. Using a once daily, fixed-dose combination of sofosbuvir (SOF) and ledipasvir (LDV), the team treated 100 patients to test the necessity of adding ribavirin (RBV) to the regimen. Results suggest a 97% sustained virological response (SVR), regardless of the addition of ribavirin.
Prior studies have already demonstrated the success of a 12- week, fixed-dose combination (FDC) with RBV for both treatment-naïve and null responders. The authorsof the study(Erick Lawitz, et al. Texas Liver Institute, San Antonio, TX, United States) therefore proposed to run the same test to see ifRBV and time were contributing significantly to the high SVR.
Sixty treatment-naïve patients were evenly and randomly assigned to one of three treatment regimens: 1) FDC for 8 weeks, 2) FDC + RBV for 8 weeks, or 3) FDC for 12 weeks. Meanwhile, 40 non-responders were split into two groups: 1) FDC or 2) FDC + RBV. All patients were HCV genotype 1. No serious adverse events were reported and minor adverse events were consistent with previous studies.
While longer-term studies are needed, the authors have demonstrated that the second generation anti-virals are sufficiency potent to eliminate HCV presence at week 12 of treatment.
The study by Lawitz and colleagues from the USA examines the interferon-free hepatitis C treatment with sofosbuvir (uridine nucleotide analogue) and ledipasvir (NS5A inhibitor) in genotype 1 patients. This combination was examined with and without ribavirin therapy, and for 8 week and 12 week durations, in both naïve and treatment experienced patients. This included patients who had previously been treated with protease inhibitors (n =40), and those naïve to treatment (n =60). The majority were genotype 1a, and 80% were IL28B-non CC. The sustained virological response rates at 12 weeks post treatment were 95-100%. Only mild adverse events were seen and only one patient discontinued therapy early.
The future of hepatitis C therapy appears to be much simpler than predicted.It seems likely that short duration (8-12 weeks) with only two agents may result in SVR in cirrhotics, null-responders and non-favourableIL28B genotypes.No doubt there will be a small number of patients that fail these simple regimens and require longer therapy, or more agents, but it appears that this will be a very small percentage.
