Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan.
Proc Natl Acad Sci U S A. 2013 May 7;110(19):7844-9. doi: 10.1073/pnas.1306138110. Epub 2013 Apr 23.
MicroRNA-122 (miR-122) facilitates hepatitis C virus replication in vitro. Serum miR-122 has been implicated as a biomarker for various liver diseases; however, its role in chronic hepatitis C remains unclear. To address this issue, 126 patients with chronic hepatitis C who completed pegylated IFN plus ribavirin therapy with sustained virologic response (SVR) or nonresponse (NR) were retrospectively included, and their pretreatment clinical profiles and treatment responses were collected. Serum miR-122 was quantified before and during treatment. Another 51 patients in SVR and NR groups were prospectively enrolled for validation. Serum miR-122 was found to be a surrogate for hepatic miR-122 and positively correlated with hepatic necroinflammation. Patients who showed complete early virologic response and SVR had significantly higher pretreatment serum miR-122 levels than those with NR (P = 0.001 and P = 0.008, respectively), especially in subgroups of patients with hepatitis C virus genotype 2 and IL-28B rs8099917 TT genotype. Patients with IL-28B TT genotype had significantly better treatment responses and higher pretreatment serum miR-122 level than those with GT or GG genotypes. Univariate analysis showed that pretreatment body mass index, γ-glutamyl transpeptidase, triglyceride, IL-28B TT genotype, and serum miR-122 are predictors for SVR. Multivariate analysis specifically in IL-28B TT genotype demonstrated that pretreatment serum miR-122 independently predicted SVR. The validation cohort confirmed a significantly greater pretreatment serum miR-122 level in patients with SVR compared with NR (P = 0.025). In conclusion, serum miR-122 may serve as a surrogate of hepatic miR-122, and a higher pretreatment serum miR-122 level can help predict virologic responses to pegylated IFN plus ribavirin therapy.
miR-122（miR-122）促进丙型肝炎病毒在体外复制。血清 miR-122 已被认为是各种肝病的生物标志物；然而，其在慢性丙型肝炎中的作用仍不清楚。为了解决这个问题，回顾性纳入了 126 例完成聚乙二醇干扰素加利巴韦林治疗并获得持续病毒学应答（SVR）或无应答（NR）的慢性丙型肝炎患者，收集了他们治疗前的临床特征和治疗反应。在治疗前和治疗期间定量了血清 miR-122。另前瞻性纳入了 SVR 和 NR 组的 51 例患者进行验证。发现血清 miR-122 是肝 miR-122 的替代物，与肝坏死性炎症呈正相关。完全早期病毒学应答和 SVR 的患者治疗前血清 miR-122 水平显著高于 NR 患者（P=0.001 和 P=0.008），特别是丙型肝炎病毒基因型 2 和 IL-28B rs8099917 TT 基因型患者。IL-28B TT 基因型患者的治疗反应显著更好，治疗前血清 miR-122 水平也显著高于 GT 或 GG 基因型患者。单因素分析显示，治疗前体重指数、γ-谷氨酰转肽酶、甘油三酯、IL-28B TT 基因型和血清 miR-122 是 SVR 的预测因素。在 IL-28B TT 基因型中进行的多因素分析显示，治疗前血清 miR-122 可独立预测 SVR。验证队列证实 SVR 患者治疗前血清 miR-122 水平显著高于 NR（P=0.025）。总之，血清 miR-122 可能作为肝 miR-122 的替代物，较高的治疗前血清 miR-122 水平有助于预测聚乙二醇干扰素加利巴韦林治疗的病毒学反应。
