Systemic and Intrahepatic Interferon-Gamma-Inducible Protein 10 kDa Predicts the First-Phase Decline in Hepatitis C Virus RNA and Overall Viral Response to Therapy in Chronic Hepatitis C
Systemic and Intrahepatic Interferon-Gamma-Inducible Protein 10 kDa Predicts the First-Phase Decline in Hepatitis C Virus RNA and Overall Viral Response to Therapy in Chronic Hepatitis C
复制标题
DOI：
10.1002/hep.23509
复制
发表时间：
2010-05-01
期刊：
影响因子：
13.5
通讯作者：
Lagging, Martin
中科院分区：
文献类型：
--
作者：
Askarieh, Galia;Alsio, Asa;Lagging, Martin
在联合治疗慢性丙型肝炎病毒（HCV）感染时，高水平的干扰素-γ-诱导蛋白10 kDa（IP-10）预示着不良结局，但关于IP-10对治疗期间HCV RNA减少的影响的细节仍不清楚。在本研究中，我们在III期治疗试验（DITTO-HCV）中将肝活检（n = 73）和血浆（n = 265）中IP-10的治疗前水平与整个治疗期间的HCV RNA相关联。在所有患者中，低水平的血浆或肝内IP-10与治疗前24小时内HCV RNA的显著降低密切相关（分别为P < 0.0001和P = 0.002）以及当患者被分为基因型1或4时，（P = 0.0008和P = 0.01）和2或3（P = 0.002和P = 0.02）。低血浆IP-10水平也可预测HCV RNA的绝对减少（P < 0.0001）和治疗前4天HCV RNA的最大减少（P < 0.0001）以及持续的病毒学应答（基因型1/4; P < 0.0001）。为了证实早期病毒下降与IP-10之间的关系，分析了来自HCV基因型2/3的独立IV期试验（NORDynamic试验; n = 382）的治疗前血浆样本。结果证实了IP-10与治疗后HCV RNA立即减少之间的相关性（P = 0.006）。相比之下，肝脏或血浆中IP-10的预处理水平在第8天和第29天之间不影响HCV RNA的下降，即，第二阶段下降，或任何这些队列中的更晚时间点。结论：在慢性丙型肝炎患者中，低水平的肝内和全身IP-10预测在聚乙二醇干扰素和利巴韦林治疗HCV基因型期间HCV RNA的第一阶段下降是有利的。（《肝脏学》2010年;51：1523-1530）
High systemic levels of interferon-gamma-inducible protein 10 kDa (IP-10) at onset of combination therapy for chronic hepatitis C virus (HCV) infection predict poor outcome, but details regarding the impact of IP-10 on the reduction of HCV RNA during therapy remain unclear. In the present study, we correlated pretreatment levels of IP-10 in liver biopsies (n = 73) and plasma (n = 265) with HCV RNA throughout therapy within a phase III treatment trial (DITTO-HCV). Low levels of plasma or intrahepatic IP-10 were strongly associated with a pronounced reduction of HCV RNA during the first 24 hours of treatment in all patients (P < 0.0001 and P = 0.002, respectively) as well as when patients were grouped as genotype 1 or 4 (P = 0.0008 and P = 0.01) and 2 or 3 (P = 0.002, and P = 0.02). Low plasma levels of IP-10 also were predictive of the absolute reduction of HCV RNA (P < 0.0001) and the maximum reduction of HCV RNA in the first 4 days of treatment (P < 0.0001) as well as sustained virological response (genotype 1/4; P < 0.0001). To corroborate the relationship between early viral decline and IP-10, pretreatment plasma samples from an independent phase IV trial for HCV genotypes 2/3 (NORDynamIC trial; n = 382) were analyzed. The results confirmed an association between IP-10 and the immediate reduction of HCV RNA in response to therapy (P = 0.006). In contrast, pretreatment levels of IP-10 in liver or in plasma did not affect the decline of HCV RNA between days 8 and 29, i.e., the second-phase decline, or later time points in any of these cohorts. Conclusion: In patients with chronic hepatitis C, low levels of intrahepatic and systemic IP-10 predict a favorable first-phase decline of HCV RNA during therapy with pegylated interferon and ribavirin for genotypes of HCV. (HEPATOLOGY 2010;51:1523-1530.)