Martin Michelle T, Deming Paulina
University of Illinois Hospital & Health Sciences System, Chicago, Illinois.
University of Illinois at Chicago, College of Pharmacy, Chicago, Illinois.
Pharmacotherapy. 2017 Jun;37(6):735-747. doi: 10.1002/phar.1933. Epub 2017 May 12.
The efficacy of hepatitis C virus (HCV) treatment has increased over the last 5 years to nearly 100% for many patient groups. Patients with genotype (GT) 3 HCV infection, however, and specifically cirrhotic or treatment-experienced patients, have lower sustained virologic response (SVR) rates than patients with other GTs. Because GT 3 presents more clinical challenges than other GTs, this review focuses on the evolution and efficacy of direct-acting antiviral (DAA) treatment options for HCV GT 3 infection after the historical standard of care with pegylated interferon and ribavirin. Our objective was to review the SVR rates with available and late-pipeline DAAs for HCV GT 3 infection and discuss challenges with successful GT 3 treatment. Authors performed a literature search of the PubMed/MEDLINE database (inception to March 27, 2017) and narrowed the field to clinical trials published in English. Trials that evaluated alternative treatments, non-DAA historical treatment, and DAAs not currently indicated for HCV were excluded. Trials only involving patients with human immunodeficiency virus/HCV coinfection were also excluded. Additional trials were identified from a review of the ClinicalTrials.gov database. Authors further identified references from a review of literature citations and reviewed annual meeting abstracts from the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver for pipeline and real-world GT 3 data. Phase III trial data were not available to support all GT 3 treatment recommendations found in the guidelines. The SVR rates were lower in treatment-experienced and cirrhotic patients with GT 3 than other HCV populations. Treatment failure was associated with resistance to current treatment regimens. Clinical studies included patients with various levels of advanced liver disease, but few patients with decompensated cirrhosis were represented. Recent advances in pharmacologic treatment with DAAs have greatly increased SVR rates in patients with all HCV GTs, but SVR rates for treatment-experienced cirrhotic patients with GT 3 are lower than for other GTs. Given the limited data and observed SVR rates in this patient population, the optimal therapy for patients with decompensated cirrhotic GT 3 HCV infection is not yet established. Newer agents and recommendations regarding baseline resistance are likely to evolve treatment strategies in the near future.
在过去5年中，丙型肝炎病毒（HCV）治疗的疗效有所提高，许多患者群体的治愈率接近100%。然而，基因3型（GT 3）HCV感染患者，尤其是肝硬化患者或经治患者，其持续病毒学应答（SVR）率低于其他基因型患者。由于GT 3比其他基因型带来更多临床挑战，本综述聚焦于在聚乙二醇化干扰素和利巴韦林这一历史标准治疗方案之后，针对GT 3感染的直接抗病毒药物（DAA）治疗方案的演变及疗效。我们的目的是回顾用于GT 3感染的现有及处于后期研发阶段的DAA的SVR率，并讨论GT 3成功治疗面临的挑战。作者检索了PubMed/MEDLINE数据库（建库至2017年3月27日），并将范围缩小至以英文发表的临床试验。评估替代治疗、非DAA历史治疗以及当前未被批准用于HCV的DAA的试验被排除。仅纳入人类免疫缺陷病毒/HCV合并感染患者的试验也被排除。通过检索ClinicalTrials.gov数据库又识别出了其他试验。作者还从文献引用回顾中识别参考文献，并查阅了美国肝病研究协会和欧洲肝病研究协会年会摘要中关于GT 3的研发中及真实世界数据。尚无III期试验数据支持指南中所有GT 3治疗推荐。GT 3的经治患者和肝硬化患者的SVR率低于其他HCV人群。治疗失败与对当前治疗方案的耐药相关。临床研究纳入了不同程度晚期肝病患者，但失代偿期肝硬化患者较少。DAA药物治疗的最新进展大幅提高了所有HCV基因型患者的SVR率，但GT 3的经治肝硬化患者的SVR率低于其他基因型。鉴于该患者群体的数据有限及观察到的SVR率，失代偿期肝硬化GT 3 HCV感染患者的最佳治疗方案尚未确立。新型药物及关于基线耐药的推荐可能在不久的将来改变治疗策略。
