Braun D L, Rauch A, Durisch N, Eberhard N, Anagnostopoulos A, Ledergerber B, Metzner K J, Böni J, Weber R, Fehr J
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
HIV Med. 2014 Nov;15(10):625-30. doi: 10.1111/hiv.12166. Epub 2014 Jun 4.
The efficacy of current hepatitis C virus (HCV) triple therapy, including a protease inhibitor, is limited in HIV/HCV-coinfected patients with advanced liver fibrosis and nonresponse to previous peginterferon-ribavirin. These patients have a low chance (only 30%) of achieving a sustained virological response (SVR) during triple therapy and cannot wait for next-generation anti-HCV drugs. In a pilot study, we investigated the efficacy of a lead-in therapy with silibinin before triple therapy in difficult-to-treat patients.
Inclusion criteria were HIV/HCV coinfection with advanced liver fibrosis and documented failure of previous peginterferon-ribavirin treatment. Intervention was lead-in therapy with intravenous silibinin 20 mg/kg/day for 14 days. Subsequently, peginterferon-ribavirin combined with telaprevir was initiated for 12 weeks, followed by peginterferon-ribavirin dual therapy until week 48 after initiation of triple therapy. The outcome measurements were HCV RNA after silibinin lead-in, at weeks 2, 4 and 12 of triple therapy, and SVR at week 24 after the end of treatment.
We examined six HIV/HCV-coinfected patients (four infected with genotype 1a). All had fibrosis grade METAVIR ≥F3 and were on fully suppressive antiretroviral therapy. Mean HCV RNA decline after silibinin therapy was 2.6 log10 IU/mL (range 2-3 log10 IU/mL). Five of the six patients were virologically suppressed at weeks 2 and 4, and all six at week 12 of triple therapy. One experienced a viral breakthrough thereafter. Four of five patients (80%) showed an SVR 24. One patient had an SVR 12 but has not yet reached week 24.
A lead-in with silibinin before triple therapy is highly effective and increases the probability of HCV treatment success in difficult-to-treat HIV/HCV-coinfected patients with advanced liver fibrosis and previous failure of peginterferon-ribavirin.
目前包括蛋白酶抑制剂在内的丙型肝炎病毒（HCV）三联疗法，在合并感染HIV且患有晚期肝纤维化、对既往聚乙二醇干扰素-利巴韦林治疗无反应的患者中疗效有限。这些患者在三联疗法期间实现持续病毒学应答（SVR）的几率较低（仅30%），且无法等待下一代抗HCV药物。在一项试点研究中，我们调查了在三联疗法前使用水飞蓟宾进行导入治疗对难治性患者的疗效。
纳入标准为合并感染HIV/HCV且患有晚期肝纤维化，并有既往聚乙二醇干扰素-利巴韦林治疗失败的记录。干预措施为静脉注射水飞蓟宾20mg/kg/天，持续14天进行导入治疗。随后，开始聚乙二醇干扰素-利巴韦林联合特拉匹韦治疗12周，之后进行聚乙二醇干扰素-利巴韦林双联治疗，直至三联疗法开始后第48周。观察指标为水飞蓟宾导入治疗后、三联疗法第2、4和12周时的HCV RNA，以及治疗结束后第24周时的SVR。
我们检查了6例合并感染HIV/HCV的患者（4例感染1a基因型）。所有患者的纤维化程度均为METAVIR≥F3级，且均接受完全抑制性抗逆转录病毒治疗。水飞蓟宾治疗后HCV RNA平均下降2.6 log10 IU/mL（范围为2 - 3 log10 IU/mL）。6例患者中有5例在三联疗法第2周和第4周时病毒学得到抑制，6例在三联疗法第12周时均得到抑制。此后有1例出现病毒突破。5例患者中有4例（80%）实现了SVR24。1例患者实现了SVR12，但尚未达到第24周。
在三联疗法前使用水飞蓟宾进行导入治疗非常有效，可提高对合并感染HIV/HCV、患有晚期肝纤维化且既往聚乙二醇干扰素-利巴韦林治疗失败的难治性患者的HCV治疗成功率。
