抗肿瘤坏死因子-α单克隆抗体疗法治疗严重酒精性肝炎

Anti-tumor necrosis factor-alpha monoclonal antibody therapy in severe alcoholic hepatitis.

作者信息

Tilg Herbert, Jalan Rajiv, Kaser Arthur, Davies Nathan A, Offner Felix A, Hodges Stephen J, Ludwiczek Othmar, Shawcross Deborah, Zoller Heinz, Alisa Akeel, Mookerjee Rajeshwar P, Graziadei Ivo, Datz Christian, Trauner Michael, Schuppan Detlef, Obrist Peter, Vogel Wolfgang, Williams Roger

机构信息

Department of Medicine, Division of Gastroenterology and Hepatology, University Hospital Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.

出版信息

J Hepatol. 2003 Apr;38(4):419-25. doi: 10.1016/s0168-8278(02)00442-7.

DOI:10.1016/s0168-8278(02)00442-7

PMID:12663232

Abstract

BACKGROUND/AIMS: Severe alcoholic hepatitis (AH) is associated with high mortality. Tumor necrosis factor-alpha (TNFalpha) has been demonstrated to play an important role in its pathophysiology.

METHODS

Twelve patients with biopsy-confirmed AH and a Maddrey discriminant factor >32 were treated with a single infusion of the anti-TNF monoclonal antibody Infliximab at a dose of 5mg/kg body weight. Serial measurements were made for various cytokines using specific enzyme-linked immunoassays (ELISA). In four patients, liver biopsy samples were available pretreatment and on day+28 of therapy.

RESULTS

Ten of the 12 patients are alive at a median of 15 (12-20) months. Two patients died within 30 days from septicemia. Serum bilirubin levels, Maddrey score, neutrophil count and C-reactive protein fell significantly within the first month. There was an early, though not significant, decrease in plasma levels of proinflammatory cytokines (interleukins (IL)-1beta, IL-6, IL-8, interferon-gamma), whereas plasma levels of TNFalpha remained near the sensitivity limit of the assay throughout the treatment course. While TNFalpha mRNA expression in the liver did not change, expression of IL-8, a cytokine regulated mainly by TNFalpha, was almost absent on day+28.

CONCLUSIONS

Our data suggest that randomized controlled trials of anti-TNF antibody in severe AH are warranted.

摘要

背景/目的：严重酒精性肝炎（AH）与高死亡率相关。肿瘤坏死因子-α（TNFα）已被证明在其病理生理学中起重要作用。

方法

12例经活检确诊为AH且Maddrey判别因子>32的患者接受单次静脉输注抗TNF单克隆抗体英夫利昔单抗治疗，剂量为5mg/kg体重。使用特异性酶联免疫吸附测定（ELISA）对多种细胞因子进行系列检测。4例患者在治疗前及治疗第28天可获得肝活检样本。

结果

12例患者中有10例存活，中位生存期为15（12 - 20）个月。2例患者在30天内死于败血症。血清胆红素水平、Maddrey评分、中性粒细胞计数和C反应蛋白在第一个月内显著下降。促炎细胞因子（白细胞介素（IL）-1β、IL-6、IL-8、干扰素-γ）的血浆水平早期虽无显著下降，但在整个治疗过程中，TNFα的血浆水平一直接近检测的灵敏度极限。虽然肝脏中TNFαmRNA表达未改变，但主要由TNFα调节的细胞因子IL-8在治疗第28天几乎未表达。