Kuruppu Heshan, Karunananda Maneshka, Jeewandara Chandima, Gomes Laksiri, Dissanayake D M C B, Ranatunga Chathura, Chathurangika Padukkage Harshani, Senatilleke Nushara, Warnakulasuriya Navanjana, Wickramanayake Rivindu H, Wijewickrama Ananda, Idampitiya Damayanthi, Ogg Graham S, Malavige Gathsaurie Neelika
Allergy, Immunology and Cell Biology Unit, Department of Immunology and Molecular Medicine, University of Sri Jayewardenepura, Nugegoda, Sri Lanka.
National Institute of Infectious Diseases, Angoda, Sri Lanka.
medRxiv. 2025 Mar 19:2025.03.18.25324170. doi: 10.1101/2025.03.18.25324170.
Obesity and diabetes are risk factors for severe dengue. As there are limited data on the association of obesity with liver dysfunction and oxidative stress in patients with acute dengue, we investigated liver dysfunction associated with obesity, oxidative stress and inflammatory markers, in a large cohort of patients with varying severity of acute dengue.
577 adults dengue patients with acute disease, presenting with a duration of illness ≤ 4 days, were enrolled and followed up from admission to discharge, with clinical and laboratory features recorded. Aspartate transaminase (AST), alanine transaminase (ALT), C-reactive protein, ferritin, 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) levels were measured, along with the height, weight and waist circumference.
AST, ALT, CRP and ferritin levels were significantly higher in patients with central obesity (waist circumference of ≥80cm in women or ≥90cm in men) compared to leaner individuals. ALT and CRP levels were also significantly higher in patients with a BMI of ≥ 23.9 kg/m. 4-HNE levels significantly increased with the rise in AST levels and with ALT levels although not significant. In contrast, MDA levels gradually decreased with the rise in AST levels and ALT levels. There were no differences in 4-HNE and MDA levels in relation to clinical disease severity. However, MDA levels were significantly higher in younger individuals, and leaner individuals with a normal BMI. Furthermore, MDA levels inversely correlated with serum ferritin levels, while AST, ALT and CRP levels significantly correlated ferritin levels.
4-HNE and MDA which are markers of lipid peroxidation, appear to play different roles in the pathogenesis of dengue, which should be further investigated for identification of therapeutic targets for treatment of dengue.
肥胖和糖尿病是重症登革热的危险因素。由于关于肥胖与急性登革热患者肝功能障碍和氧化应激之间关联的数据有限，我们在一大群急性登革热严重程度各异的患者中，研究了与肥胖、氧化应激和炎症标志物相关的肝功能障碍。
纳入577例急性疾病病程≤4天的成年登革热患者，从入院到出院进行随访，并记录临床和实验室特征。测量天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、C反应蛋白、铁蛋白、4-羟基壬烯醛（4-HNE）和丙二醛（MDA）水平，同时测量身高、体重和腰围。
与体型较瘦者相比，中心性肥胖（女性腰围≥80cm或男性腰围≥90cm）患者的AST、ALT、CRP和铁蛋白水平显著更高。BMI≥23.9kg/m²的患者ALT和CRP水平也显著更高。4-HNE水平随AST水平和ALT水平升高而显著增加，尽管不显著。相比之下，MDA水平随AST水平和ALT水平升高而逐渐降低。4-HNE和MDA水平与临床疾病严重程度无关。然而，MDA水平在较年轻个体和BMI正常的体型较瘦个体中显著更高。此外，MDA水平与血清铁蛋白水平呈负相关，而AST、ALT和CRP水平与铁蛋白水平显著相关。
作为脂质过氧化标志物的4-HNE和MDA在登革热发病机制中似乎发挥着不同作用，应进一步研究以确定登革热治疗的靶点。
