Department of Biochemistry, Faculty of Pharmacy, Misr International University, Cairo 1, Egypt.
World J Gastroenterol. 2012 Jul 28;18(28):3738-44. doi: 10.3748/wjg.v18.i28.3738.
To assess vitamin D (Vit D) abnormalities in hepatitis C infected patients and their relationship with interleukin (IL)-17, IL-23 and N-terminal propeptide of type III pro-collagen (PIIINP) as immune response mediators.
The study was conducted on 50 Egyptian patients (36 male, 14 female) with hepatitis C virus (HCV) infection, who visited the Hepatology Outpatient Clinic in the Endemic Disease Hospital at Cairo University. Patients were compared with 25 age- and sex-matched healthy individuals. Inclusion criteria were based on a history of liver disease with HCV genotype 4 (HCV-4) infection (as new patients or under follow-up). Based on ultrasonography, patients were classified into four subgroups; 14 with bright hepatomegaly; 11 with perihepatic fibrosis; 11 with hepatic cirrhosis; and 14 with cirrhosis and hepatocellular carcinoma (HCC). Total Vit D (i.e., 25-OH-Vit D) and active Vit D [i.e., 1,25-(OH)₂-Vit D] assays were carried out using commercial kits. IL-17, IL-23 and PIIINP levels were assayed using enzyme linked immunosorbent assay kits, while HCV virus was measured by quantitative and qualitative polymerase chain reaction.
Levels of Vit D and its active form were significantly lower in advanced liver disease (hepatic cirrhosis and/or carcinoma) patients, compared to those with bright hepatomegaly and perihepatic fibrosis. IL-17, IL-23 and PIIINP levels were markedly increased in HCV patients and correlated with the progression of hepatic damage. The decrease in Vit D and active Vit D was concomitant with an increase in viral load, as well as levels of IL-17, IL-23 and PIIINP among all subgroups of HCV-infected patients, compared to normal healthy controls. A significant negative correlation was evident between active Vit D and each of IL-17, IL-23 and PIIINP (r = -0.679, -0.801 and -0.920 at P < 0.001, respectively). HCV-infected men and women showed no differences with respect to Vit D levels. The viral load was negatively correlated with Vit D and active Vit D (r = -0.084 and -0.846 at P < 0.001, respectively), and positively correlated with IL-17, IL-23 and PIIINP (r = 0.951, 0.922 and 0.94 at P < 0.001, respectively). Whether the deficiency in Vit D was related to HCV-induced chronic liver disease or was a predisposing factor for a higher viral load remains to be elucidated.
The negative correlations between Vit D and IL-17, IL-23 and PIIINP highlight their involvement in the immune response in patients with HCV-4-related liver diseases in Egypt.
评估丙型肝炎感染患者的维生素 D（Vit D）异常及其与白细胞介素（IL）-17、IL-23 和 III 型前胶原氨基端肽（PIIINP）作为免疫反应介质的关系。
本研究纳入了 50 名埃及丙型肝炎病毒（HCV）感染患者（36 名男性，14 名女性），这些患者在开罗大学传染病医院的肝病门诊就诊。将患者与 25 名年龄和性别匹配的健康个体进行比较。纳入标准是基于有 HCV 基因型 4（HCV-4）感染（作为新发病例或随访病例）的肝病病史。根据超声检查结果，患者分为四个亚组：14 例为肝肿大伴明亮；11 例为肝周纤维化；11 例为肝硬化；14 例为肝硬化伴肝细胞癌（HCC）。使用商业试剂盒检测总 Vit D（即 25-OH-Vit D）和活性 Vit D [即 1,25-（OH）₂-Vit D]。使用酶联免疫吸附测定试剂盒检测白细胞介素 17（IL-17）、白细胞介素 23（IL-23）和 PIIINP 水平，而 HCV 病毒则通过定量和定性聚合酶链反应进行测量。
与肝肿大伴明亮和肝周纤维化的患者相比，晚期肝病（肝硬化和/或肝癌）患者的 Vit D 和其活性形式水平显著降低。HCV 患者的 IL-17、IL-23 和 PIIINP 水平明显升高，并与肝损伤的进展相关。在所有 HCV 感染患者亚组中，Vit D 和活性 Vit D 的降低与病毒载量的增加以及 IL-17、IL-23 和 PIIINP 的水平同时增加有关，与正常健康对照组相比。在所有 HCV 感染患者亚组中，活性 Vit D 与 IL-17、IL-23 和 PIIINP 之间均存在显著负相关（r = -0.679、-0.801 和 -0.920，P < 0.001）。HCV 感染的男性和女性在 Vit D 水平方面没有差异。病毒载量与 Vit D 和活性 Vit D 呈负相关（r = -0.084 和 -0.846，P < 0.001），与 IL-17、IL-23 和 PIIINP 呈正相关（r = 0.951、0.922 和 0.94，P < 0.001）。Vit D 缺乏是否与 HCV 引起的慢性肝病有关，或者是否是病毒载量较高的一个诱发因素，仍有待阐明。
Vit D 与白细胞介素 17、白细胞介素 23 和 PIIINP 之间的负相关表明它们在埃及 HCV-4 相关肝病患者的免疫反应中发挥作用。
