Sharma Surendra K, Balamurugan Arumugam, Saha Pradip Kumar, Pandey Ravindra M, Mehra Narinder K
Department of Medicine, All India Institute of Medical Sciences, New Delhi, India.
Am J Respir Crit Care Med. 2002 Oct 1;166(7):916-9. doi: 10.1164/rccm.2108091.
Though several risk factors for the development of hepatotoxicity due to antituberculosis drugs have been suggested, involvement of genetic factors is not fully established. We have studied the major histocompatibility complex (MHC) class II alleles and clinical risk factors for the development of hepatotoxicity in 346 North Indian patients with tuberculosis undergoing antituberculosis treatment. Of these, 56 patients developed drug-induced hepatotoxicity (DIH group), whereas the remaining 290 patients did not (non-DIH group). The DIH group was comparatively older, had lower pretreatment serum albumin, and a higher frequency of moderately/far advanced disease radiographically than the latter. Further, patients with high alcohol intake had threefold higher odds of developing hepatotoxicity. In multivariate logistic regression analysis, older age (odds ratio [OR] 1.2), moderately/far advanced disease (OR 2.0), serum albumin < 3.5 g/dl (OR 2.3), absence of HLA-DQA10102 (OR 4.0), and presence of HLA-DQB10201 (OR 1.9) were independent risk factors for DIH. Our results suggest that the risk of hepatotoxicity from antituberculosis drugs is influenced by clinical and genetic factors.
尽管已经提出了几种抗结核药物导致肝毒性的危险因素，但遗传因素的作用尚未完全明确。我们研究了346名接受抗结核治疗的北印度结核病患者中主要组织相容性复合体（MHC）II类等位基因与肝毒性发生的临床危险因素。其中，56名患者发生了药物性肝毒性（DIH组），而其余290名患者未发生（非DIH组）。与后者相比，DIH组年龄相对较大，治疗前血清白蛋白较低，影像学上中度/晚期疾病的发生率较高。此外，高酒精摄入量的患者发生肝毒性的几率高出三倍。在多因素逻辑回归分析中，年龄较大（比值比[OR] 1.2）、中度/晚期疾病（OR 2.0）、血清白蛋白<3.5 g/dl（OR 2.3）、缺乏HLA-DQA10102（OR 4.0）以及存在HLA-DQB1020
