Willemse S B, Jansen L, de Niet A, Sinnige M J, Takkenberg R B, Verheij J, Kootstra N A, Reesink H W
Department of Gastroenterology and Hepatology, Academic Medical Center, The Netherlands.
Department of Gastroenterology and Hepatology, Academic Medical Center, The Netherlands.
Antiviral Res. 2016 Jul;131:148-55. doi: 10.1016/j.antiviral.2016.05.002. Epub 2016 May 4.
Interferon-y-inducible protein-10 (IP-10), also called CXCL10, is produced by different types of cells such as monocytes, neutrophils and hepatocytes. IP-10 functions as an inflammatory cytokine, which after binding to its receptor CXCR3, expressed on T-lymphocytes, leads to immune activation. We aimed to establish if IP-10 expression in liver tissue and in plasma of chronic hepatitis B (CHB) patients correlated with each other and further to investigate if IP-10 levels before and during therapy with peginterferon and adefovir could predict treatment outcome in CHB patients.
A total of 86 CHB patients (41 HBeAg-positive and 45 HBeAg-negative) received combination therapy of peginterferon and adefovir for 48 weeks. Combined Response (CR) (HBeAg-negativity, HBV-DNA ≤ 2000 IU/mL, ALT normalization) and non-response (NR) were assessed at Week 72. Plasma IP-10 levels were measured at baseline and during treatment at Day 3 (D3) and Week 1 (W1). Pre-treatment liver biopsies from 40 of 86 patients were obtained and stored in liquid nitrogen for the analysis of intrahepatic IP-10 mRNA expression.
CR was achieved in 14/41 HBeAg-positive and 17/45 HBeAg-negative patients. Mean baseline plasma IP-10 levels were significantly higher in HBeAg-positive patients with CR than NR (3.20 vs 3.00 log pg/mL p = 0.03); but not in HBeAg-negative patients. Baseline IP-10 levels correlated with ALT-levels in HBeAg-positive and -negative patients (both p < 0.001), and with a decline of HBsAg-levels of ≥0.5 log IU/mL at Week 12 in HBeAg-positive patients (p = 0.001). Plasma IP-10 levels were associated with intrahepatic IP-10 mRNA expression, however, more strongly in HBeAg-positive (R = 0.79, p < 0.001) than in HBeAg-negative patients (R = 0.53, p = 0.011). IP-10 levels only correlated with HAI-scores in HBeAg-positive patients (R = 0.40 p = 0.025). Mean plasma IP-10 levels of both HBeAg-positive and -negative patients increased significantly at D3 compared to baseline (+0.30 log pg/mL p = 0.003), to then decline subsequently at W1 to a level still significantly higher than baseline (+0.14 log pg/mL p < 0.001). The increase of IP-10 was significantly higher in HBeAg-positive patients with NR than in those with CR (+0.35 versus +0.11 log pg/mL p = 0.003).
Baseline plasma IP-10 levels and IP-10 mRNA expression in the liver are correlated with each other, suggesting that plasma IP-10 reflects intrahepatic immune activation. Higher IP-10 levels at baseline seem to be associated with CR in HBeAg-positive patients treated with peginterferon and adefovir, but not in HBeAg-negative patients.
干扰素γ诱导蛋白10（IP - 10），也称为CXCL10，由单核细胞、中性粒细胞和肝细胞等不同类型的细胞产生。IP - 10作为一种炎性细胞因子，与T淋巴细胞上表达的受体CXCR3结合后可导致免疫激活。我们旨在确定慢性乙型肝炎（CHB）患者肝组织和血浆中IP - 10的表达是否相互关联，并进一步研究聚乙二醇干扰素和阿德福韦治疗前及治疗期间的IP - 10水平是否可预测CHB患者的治疗结局。
86例CHB患者（41例HBeAg阳性和45例HBeAg阴性）接受聚乙二醇干扰素和阿德福韦联合治疗48周。在第72周评估联合应答（CR）（HBeAg阴性、HBV - DNA≤2000 IU/mL、ALT正常化）和无应答（NR）情况。在基线以及治疗第3天（D3）和第1周（W1）时检测血浆IP - 10水平。从86例患者中的40例获取治疗前肝活检组织并储存于液氮中，用于分析肝内IP - 10 mRNA表达。
41例HBeAg阳性患者中有14例、45例HBeAg阴性患者中有17例实现CR。CR的HBeAg阳性患者的平均基线血浆IP - 10水平显著高于NR患者（3.
