Thornton Karla, Deming Paulina, Manch Richard A, Moore Ann, Kohli Anita, Gish Robert, Sussman Norman L, Khaderi Saira, Scott John, Mera Jorge, Box Terry, Qualls Clifford, Sedillo Miranda, Arora Sanjeev
Division of Infectious Diseases, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
College of Pharmacy-Department of Pharmacy Practice, Project ECHO, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, USA.
Hepatol Int. 2016 Jul;10(4):624-31. doi: 10.1007/s12072-016-9725-6. Epub 2016 Apr 20.
Historically, chronic hepatitis C virus (HCV) treatment was response-guided. Clinical trials with sofosbuvir indicated on-treatment virologic response was not predictive of sustained virologic response (SVR) and hence response-guided therapy (RGT) was abandoned. The purpose of this study is to examine the association between on-treatment 4-week HCV RNA and SVR in patients treated in real-world practice.
The study is a retrospective analysis of consecutive patients started on treatment with a sofosbuvir-containing regimen, January 1, 2014 through August 20, 2014, for HCV genotype 1-6 infection. Patients were treated by HCV specialists at 6 centers in the Project ECHO (Extension for Community Healthcare Outcomes) HCV Collaborative or in the community by primary care clinicians mentored by HCV specialists through Project ECHO. Patients were included if they were over 18 years, had evidence of chronic HCV, and were started on a sofosbuvir-containing regimen. The aspartate aminotransferase:platelet ratio index (APRI) was used to estimate fibrosis. The main outcome measures were 4-week HCV RNA and SVR.
Overall SVR was 82.5 %. At week 4, HCV RNA was detected in 27.4 % of patients. Stepwise multivariable logistic-regression analyses identified APRI > 1.0, male sex, genotype 3, and detectable on treatment 4-week HCV RNA as independent predictors of failure to achieve SVR.
In a real-world setting, a significant proportion of sofosbuvir treated patients have detectable on-treatment 4-week HCV RNA. Detectable on-treatment 4-week HCV RNA is associated with virologic failure. More data are needed to formulate guidance for RGT with newly available HCV therapies.
在过去，慢性丙型肝炎病毒（HCV）治疗是基于反应指导的。索磷布韦的临床试验表明，治疗期间病毒学反应并不能预测持续病毒学反应（SVR），因此基于反应指导的治疗（RGT）被摒弃。本研究的目的是在实际临床实践中，探讨治疗4周时的HCV RNA水平与SVR之间的关联。
本研究是一项回顾性分析，纳入了2014年1月1日至2014年8月20日期间开始接受含索磷布韦方案治疗的连续HCV 1-6型感染患者。患者由ECHO项目（社区医疗成果扩展项目）HCV协作组的6个中心的HCV专家进行治疗，或由HCV专家通过ECHO项目指导的社区初级保健临床医生在社区进行治疗。纳入标准为年龄超过18岁、有慢性HCV感染证据且开始接受含索磷布韦方案治疗的患者。采用天冬氨酸转氨酶与血小板比值指数（APRI）评估肝纤维化程度。主要观察指标为治疗4周时的HCV RNA水平和SVR。
总体SVR为82.5%。在治疗第4周时，27.4%的患者检测到HCV RNA。逐步多变量逻辑回归分析确定，APRI>1.0、男性、3型基因型以及治疗4周时可检测到HCV RNA是未实现SVR的独立预测因素。
在实际临床环境中，相当一部分接受索磷布韦治疗的患者在治疗4周时可检测到HCV RNA。治疗4周时可检测到HCV RNA与病毒学失败相关。需要更多数据来制定关于使用新的HCV治疗方法进行RGT的指导建议。
