Hepatology Unit, Department of Internal Medicine, Minia University Hospital, El-Minia, Egypt.
Endocrinology Unit, Department of Internal Medicine, Minia University Hospital, El-Minia, Egypt.
Med Princ Pract. 2018;27(2):115-121. doi: 10.1159/000487308. Epub 2018 Jan 31.
To investigate the possible role of signal transducer and activator of transcription 5 (STAT5) in the pathogenesis of liver fibrosis in Egyptian patients with chronic hepatitis C (CHC) virus infection and its relation to hepatic stellate cells (HSC).
Sixty-five patients (46 males and 19 females) were divided into 4 groups based on the severity of fibrosis as detected by Fibroscan as follows: F1, n = 15; F2, n = 21; F3, n = 13; and F4, n = 16. Twenty age- and gender-matched healthy persons volunteered as controls. The serum levels of STAT5, TGF-β1, α-smooth muscle actin (α-SMA), fasting blood sugar, and fasting insulin, as well as homeostasis model assessment of insulin resistance (HOMA-IR), were determined and compared for all groups. The usefulness of the studied serum biomarkers for predicting liver fibrosis was evaluated using a receiver operating characteristic curve.
Serum levels of STAT5 were significantly lower in patients compared to controls (9.69 ± 5.62 vs. 14.73 ± 6.52, p ≤ 0.001); on the contrary, TGF-β1, α-SMA, and HOMA-IR were significantly higher in patients compared to controls (mean: 1,796.04 vs. 1,636.94; 14.94 vs. 8.1; and 7.91 vs. 4.18; p ≤ 0.01 and 0.001, respectively). TGF-β1 and α-SMA showed a progressive increase with advancing severity of hepatic fibrosis (mean TGF-β1: 2,058.4 in F1-F2 and 1,583.8 in F3-F4, p ≤ 0.04; mean α-SMA: 13.59 in F1-F2 and 16.62 in F3-F4, p ≤ 0.05). STAT5 had a significant negative correlation with TGF-β1 (p ≤ 0.001), while no correlation was detected with α-SMA (p ≤ 0.8).
STAT5 may play a significant role in hepatic fibrogenesis through the induction of TGF-β1 but not through the activation of hepatic stellate cells.
探讨信号转导和转录激活因子 5（STAT5）在埃及慢性丙型肝炎病毒（CHC）感染患者肝纤维化发病机制中的可能作用及其与肝星状细胞（HSC）的关系。
根据 Fibroscan 检测的纤维化严重程度，将 65 例患者（46 名男性和 19 名女性）分为 4 组：F1 组，n = 15；F2 组，n = 21；F3 组，n = 13；F4 组，n = 16。20 名年龄和性别匹配的健康人自愿作为对照组。比较所有组的血清 STAT5、TGF-β1、α-平滑肌肌动蛋白（α-SMA）、空腹血糖和空腹胰岛素水平，以及稳态模型评估的胰岛素抵抗（HOMA-IR）。使用受试者工作特征曲线评估研究血清生物标志物预测肝纤维化的有用性。
与对照组相比，患者的血清 STAT5 水平显著降低（9.69 ± 5.62 比 14.73 ± 6.52，p ≤ 0.001）；相反，TGF-β1、α-SMA 和 HOMA-IR 患者组显著高于对照组（均值：1796.04 比 1636.94；14.94 比 8.1；7.91 比 4.18；p ≤ 0.01 和 0.001）。TGF-β1 和 α-SMA 随着肝纤维化严重程度的进展而逐渐增加（TGF-β1 均值：F1-F2 为 2058.4，F3-F4 为 1583.8，p ≤ 0.04；α-SMA 均值：F1-F2 为 13.59，F3-F4 为 16.62，p ≤ 0.05）。STAT5 与 TGF-β1 呈显著负相关（p ≤ 0.001），而与 α-SMA 无相关性（p ≤ 0.8）。
STAT5 可能通过诱导 TGF-β1 而不是通过激活肝星状细胞在肝纤维化发生中发挥重要作用。
