在世界各地，百万计人感染了丙型肝炎病毒（HCV），HCV可导致肝硬化和肝癌症。直接作用的抗病毒剂能抑制病毒蛋白，并已成功地用于治疗HCV。
不幸的是，抗病毒治疗在一些患者中失败，导致丙型肝炎病毒复发。
发表在Journal of Clinical Investigation杂志的一项研究确定了一种标记，它可以识别患者在抗病毒治疗后是否可能有HCV复发。主要研究人员Shyamasundaran Kottilil和美国国家卫生研究院的同事评价抗病毒药物治疗丙型肝炎病毒感染者的免疫反应。
结果发现那些I型干扰素表达增加的治疗患者更有可能免于复发。无法维持I型干扰素的患者更可能有HCV复发。这项研究提供了一个潜在的标记，以确定患者是否易发生HCV复发。
Endogenous intrahepatic IFNs and association with IFN-free HCV treatment outcome
Eric G. Meissner, et al.
BACKGROUND. Hepatitis C virus (HCV) infects approximately 170 million people worldwide and may lead to cirrhosis and hepatocellular carcinoma in chronically infected individuals. Treatment is rapidly evolving from IFN-α–based therapies to IFN-α–free regimens that consist of directly acting antiviral agents (DAAs), which demonstrate improved efficacy and tolerability in clinical trials. Virologic relapse after DAA therapy is a common cause of treatment failure; however, it is not clear why relapse occurs or whether certain individuals are more prone to recurrent viremia.
METHODS. We conducted a clinical trial using the DAA sofosbuvir plus ribavirin (SOF/RBV) and performed detailed mRNA expression analysis in liver and peripheral blood from patients who achieved either a sustained virologic response (SVR) or relapsed.
RESULTS. On-treatment viral clearance was accompanied by rapid downregulation of IFN-stimulated genes (ISGs) in liver and blood, regardless of treatment outcome. Analysis of paired pretreatment and end of treatment (EOT) liver biopsies from SVR patients showed that viral clearance was accompanied by decreased expression of type II and III IFNs, but unexpectedly increased expression of the type I IFN IFNA2. mRNA expression of ISGs was higher in EOT liver biopsies of patients who achieved SVR than in patients who later relapsed.
CONCLUSION. These results suggest that restoration of type I intrahepatic IFN signaling by EOT may facilitate HCV eradication and prevention of relapse upon withdrawal of SOF/RBV.
TRIAL REGISTRATION. ClinicalTrials.gov NCT01441180.
FUNDING. Intramural Programs of the National Institute of Allergy and Infectious Diseases, National Institutes of Health Clinical Center, and National Cancer Institute; German Research Foundation.
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