Del Ben M, Polimeni L, Baratta F, Bartimoccia S, Carnevale R, Loffredo L, Pignatelli P, Violi F, Angelico F
Department of Internal Medicine and Medical Specialities, Sapienza University, Rome, Italy.
Department of Internal Medicine and Medical Specialities, Sapienza University, Rome, Italy ; Department of Public Health and Infectious Disease, Sapienza University, Rome, Italy.
Int J Hepatol. 2014;2014:784985. doi: 10.1155/2014/784985. Epub 2014 Jan 29.
Background & Aims. Hepatocyte apoptosis may play a role in progression of nonalcoholic fatty liver and oxidative stress seems one of the key mechanisms responsible for liver damage. The aim was to determine the association of oxidative stress with cytokeratin-18 M30 fragment levels, a marker of hepatocyte apoptosis. Methods. Steatosis severity was defined according to Hamaguchi's echographic criteria in 209 patients with nonalcoholic fatty liver. Serum cytokeratin-18, urinary 8-iso-prostaglandin F2 α , soluble NOX2-derived peptide, and adiponectin were measured. Results. Serum cytokeratin-18 progressively increased with steatosis severity (from 169.5 (129.3/183.8) to 176 (140/190) and 180 (169.5/192.5) μ IU/mL in mild, moderate, and severe steatosis, respectively; P < 0.01). After stratification by cytokeratin-18 tertiles, a significant progression of body mass index, HOMA-IR, triglycerides, urinary 8-iso-PGF2 α , soluble NOX2-derived peptide, and of the prevalence of diabetes and severe steatosis was found, while HDL-cholesterol and adiponectin progressively decreased. A positive correlation between cytokeratin-18 and body mass index, HOMA-IR, Hamaguchi's score, urinary 8-iso-PGF2 α , and soluble NOX2-derived peptide and a negative correlation between cytokeratin-18 and HDL-cholesterol and adiponectin were found. Body mass index, adiponectin, and soluble NOX2-derived peptide were independent predictors of serum cytokeratin-18 levels (adjusted R (2) = 0.36). Conclusion. We support an association between oxidative stress and severity of liver damage in patients with nonalcoholic fatty liver.
背景与目的。肝细胞凋亡可能在非酒精性脂肪性肝病进展中起作用，氧化应激似乎是导致肝损伤的关键机制之一。本研究旨在确定氧化应激与细胞角蛋白18 M30片段水平（肝细胞凋亡标志物）之间的关联。方法。根据滨口超声标准对209例非酒精性脂肪性肝病患者的脂肪变性严重程度进行定义。检测血清细胞角蛋白18、尿8-异前列腺素F2α、可溶性NOX2衍生肽和脂联素。结果。血清细胞角蛋白18水平随脂肪变性严重程度逐渐升高（轻度、中度和重度脂肪变性患者分别为169.5（129.3/183.8）、176（140/190）和180（169.5/192.5）μIU/mL；P<0.01）。按细胞角蛋白18三分位数分层后，发现体重指数、HOMA-IR、甘油三酯、尿8-异前列腺素F2α、可溶性NOX2衍生肽以及糖尿病和重度脂肪变性患病率显著升高，而高密度脂蛋白胆固醇和脂联素逐渐降低。发现细胞角蛋白18与体重指数、HOMA-IR、滨口评分、尿8-异前列腺素F2α和可溶性NOX2衍生肽呈正相关，与高密度脂蛋白胆固醇和脂联素呈负相关。体重指数、脂联素和可溶性NOX2衍生肽是血清细胞角蛋白18水平的独立预测因素（调整后R(2)=0.36）。结论。我们支持非酒精性脂肪性肝病患者氧化应激与肝损伤严重程度之间存在关联。
