Johansson S, Talloen W, Tuefferd M, Darling J M, Scholliers A, Fanning G, Fried M W, Aerssens J
Janssen Research and Development, Beerse, Belgium.
University of North Carolina, Chapel Hill, NC, USA.
Aliment Pharmacol Ther. 2015 Nov;42(9):1111-21. doi: 10.1111/apt.13389. Epub 2015 Aug 28.
Fibrosis progression in hepatitis C virus (HCV)-infected patients varies greatly between individuals. Chemokines recruit immune cells to the infected liver and may thus play a role in the fibrosis process.
To investigate plasma levels of a diverse chemokine panel in relation to liver fibrosis.
African-American and Caucasian HCV genotype 1 infected patients were treated with peginterferon (pegIFN) and ribavirin (RBV) for 48 weeks (VIRAHEP-C cohort). Plasma levels of 13 cytokines were studied at baseline (n = 386). Subsequently, GROα levels were assessed in a sub cohort (n = 99) at baseline, and at 4 and 12 weeks after start of pegIFN/RBV treatment.
Increased severity of fibrosis (Ishak fibrosis score 0-2 vs. 3-6) was associated with increased plasma IP-10 (CXCL10) and IL-8 (CXCL8) levels, and decreased plasma levels of the chemokine growth-related oncogene (GRO, CXCL1-3). Plasma GRO levels were also positively correlated with platelet counts, and were higher in African-American as compared to Caucasian patients. In response to pegIFN/RBV treatment, GROα levels increased in Caucasian but not African-American patients from week 4 onwards.
The association with severity of fibrosis and platelet count positions plasma GRO as a potential biomarker for liver fibrosis in HCV-infected patients. The secretion of GRO by platelets may explain the correlation between GRO plasma level and platelet count. The ethnic difference in GRO levels both pre-treatment and in response to pegIFN/RBV might be driven by a genetic polymorphism in GROα associated with higher plasma levels and more common in the African-American population.
丙型肝炎病毒（HCV）感染患者的纤维化进展在个体间差异很大。趋化因子将免疫细胞募集到受感染的肝脏，因此可能在纤维化过程中发挥作用。
研究多种趋化因子水平与肝纤维化的关系。
对非裔美国人和高加索人HCV基因1型感染患者使用聚乙二醇干扰素（pegIFN）和利巴韦林（RBV）治疗48周（VIRAHEP-C队列）。在基线时（n = 386）研究13种细胞因子的血浆水平。随后，在一个亚队列（n = 99）中于基线时以及pegIFN/RBV治疗开始后4周和12周评估GROα水平。
纤维化严重程度增加（Ishak纤维化评分0 - 2与3 - 6）与血浆IP - 10（CXCL10）和IL - 8（CXCL8）水平升高以及趋化因子生长相关癌基因（GRO，CXCL1 - 3）血浆水平降低相关。血浆GRO水平也与血小板计数呈正相关，并且非裔美国患者的血浆GRO水平高于高加索患者。在pegIFN/RBV治疗后，从第4周起，高加索患者的GROα水平升高，而非裔美国患者则未升高。
血浆GRO与纤维化严重程度和血小板计数的关联使其成为HCV感染患者肝纤维化的潜在生物标志物。血小板分泌GRO可能解释了GRO血浆水平与血小板计数之间的相关性。治疗前和pegIFN/RBV治疗反应中GRO水平的种族差异可能由GROα中的基因多态性驱动，该多态性与较高的血浆水平相关且在非裔美国人群中更常见。
