Spahr Laurent, Garcia Irène, Bresson-Hadni Solange, Rubbia-Brandt Laura, Guler Reto, Olleros Maria, Chvatchko Yolande, Hadengue Antoine
Gastroenterology and Hepatology Unit, Geneva, Switzerland.
Liver Int. 2004 Dec;24(6):582-7. doi: 10.1111/j.1478-3231.2004.0967.x.
Alcoholic hepatitis (AH) is associated with dysregulated inflammatory and immune responses. interleukin-18 (IL-18), described as gamma interferon (gammaIFN)-inducible factor, and its natural antagonist, IL-18 binding protein (IL-18 BP), has not been fully studied in patients with AH. Thus, our aim was: (i) to determine plasma values of IL-18, IL-18 BP, gammaIFN, and tumor necrosis factor alpha (TNF)-alpha in patients hospitalized for biopsy-proven AH; (ii) to correlate these cytokines with the severity of AH, as assessed by Maddrey's discriminant function (DF), the degree of liver failure using the Child-Pugh score and blood neutrophils; (iii) to compare cytokines values in survivors and non-survivors.
Cytokines were measured using specific immunoassays within 7 days of admission. The diagnosis of AH was based on histology in all cases. We studied 43 cirrhotic patients with a Maddrey's DF>/=32 (severe AH), 29 patients with a score <32 (non-severe AH), 12 patients with abstinent alcoholic cirrhosis, and 10 healthy subjects.
IL-18 and TNFalpha were increased in severe AH as compared with healthy subjects. Plasma IL-18 BP was elevated in patients with severe and non-severe AH as compared with healthy subjects. gammaIFN did not differ between groups. In patients with severe and non-severe AH, IL-18, IL-18 BP, TNFalpha, but not gammaIFN, were positively correlated to DF and Child-Pugh score. Neither IL-18 nor IL-18 BP correlated to TNFalpha. Patients who died (n=10) during the hospitalization had higher IL-18 BP and TNFalpha at admission as compared with survivors (322 [172-504] vs 222 [109-441] ng/ml; 7.5 [2.2-17.3] vs 3 [0.6-20] pg/ml, P<0.01, respectively).
In cirrhotic patients with AH, IL-18, IL-18 BP, and TNFalpha correlate to the hepatitis severity and to the degree of liver failure. High IL-18 BP and TNFalpha at hospital admission in non-survivors suggest it may be of prognostic value.
酒精性肝炎（AH）与炎症和免疫反应失调有关。白细胞介素-18（IL-18），被描述为γ干扰素（γIFN）诱导因子，及其天然拮抗剂白细胞介素-18结合蛋白（IL-18 BP），在AH患者中尚未得到充分研究。因此，我们的目的是：（i）确定经活检证实为AH的住院患者血浆中IL-18、IL-18 BP、γIFN和肿瘤坏死因子α（TNF）-α的值；（ii）将这些细胞因子与AH的严重程度相关联，通过Maddrey判别函数（DF）、使用Child-Pugh评分评估的肝衰竭程度和血液中性粒细胞进行评估；（iii）比较幸存者和非幸存者的细胞因子值。
在入院7天内使用特异性免疫测定法测量细胞因子。所有病例中AH的诊断均基于组织学。我们研究了43例Maddrey DF≥32（重度AH）的肝硬化患者、29例评分<32（非重度AH）的患者、12例戒酒性肝硬化患者和10名健康受试者。
与健康受试者相比，重度AH患者的IL-18和TNFα升高。与健康受试者相比，重度和非重度AH患者的血浆IL-18 BP升高。各组之间γIFN无差异。在重度和非重度AH患者中，IL-18、IL-18 BP、TNFα，但不包括γIFN，与DF和Child-Pugh评分呈正相关。IL-18和IL-18 BP均与TNFα无相关性。住院期间死亡的患者（n = 10）入院时的IL-18 BP和TNFα高于幸存者（分别为322 [172 - 504] vs 222 [109 - 441] ng/ml；7.5 [2.2 - 17.3] vs 3 [0.6 - 20] pg/ml，P < 0.01）。
在患有AH的肝硬化患者中，IL-18、IL-18 BP和TNFα与肝炎严重程度和肝衰竭程度相关。非幸存者入院时高IL-18 BP和TNFα表明其可能具有预后价值。
