Banasch M, Knyhala K, Kollar S, Serova K, Potthoff A, Schlottmann R, Schmidt W E, Brockmeyer N H, Goetze O
Department of Internal Medicine, St Josef-Hospital, University of Bochum, Bochum, Germany.
Eur J Med Res. 2008 Sep 22;13(9):401-8.
An increasing proportion of deaths among human immunodeficiency virus (HIV)-infected persons are due to hepatic complications. Hepatitis coinfection, antiretroviral treatment and co-occurrence of metabolic risk factors contribute to hepatic mitochondrial damage manifesting in hepatic steatosis and steatohepatitis. The aim was to assess disease- and treatment-related predictors on hepatic mitochondrial dysfunction in HIV infection by means of a new (13)C-methionine breath test (MeBT).
148 HIV positive individuals with and without antiretroviral treatment (ART) [44 therapy-naives; 89 patients on combination ART and 15 patients on structured treatment interruption (STI)] and 20 HIV-negative controls were studied prospectively by MeBT.
A decay of (13)C-methionine metabolism, expressed as cumulated percentage dose recovered over 1.5h (cPDR(1.5h)), in the subgroups of treatment-naives and patients on STI compared to controls was detected (cPDR(1.5h): 3.4 +/- 1.3% and 4.0 +/- 2.4% vs. 6.3 +/- 1.2%; p<0.01). Multivariate analyses including metabolic, treatment- and disease-related variables showed that antiretroviral treatment with stavudine, didanosine or zalcitabine and treatment-naivety were best predictors of a reduced MeBT result (cPDR(1.5h)) (beta = -0.56 and -0.50, p<0.05). CD4 count had only a minor association (beta = 0.15, p<0.05). No other variable including disease and treatment duration was associated with MeBT outcome. These factors explained 39% of the variance of MeBT results (p<0.05).
Therapy naivety and treatment with d-drugs were the best predictors of poor MeBT outcome. MeBT may be proposed as a feasible, noninvasive diagnostic instrument for clinical assessment of hepatic mitochondrial function and early detection of drug-induced mitochondriotoxity in chronic HIV infection.
人类免疫缺陷病毒（HIV）感染者中，因肝脏并发症导致的死亡比例日益增加。合并感染肝炎、抗逆转录病毒治疗以及代谢风险因素的共同存在，会导致肝脏线粒体损伤，表现为肝脂肪变性和脂肪性肝炎。本研究旨在通过新型的（13）C-蛋氨酸呼气试验（MeBT）评估HIV感染中与疾病和治疗相关的因素对肝脏线粒体功能障碍的预测作用。
对148例接受或未接受抗逆转录病毒治疗（ART）的HIV阳性个体[44例初治患者；89例接受联合ART治疗的患者以及15例接受结构化治疗中断（STI）的患者]和20例HIV阴性对照者进行了MeBT前瞻性研究。
与对照组相比，初治患者组和接受STI治疗的患者组中，（13）C-蛋氨酸代谢衰减，以1.5小时内累积回收剂量百分比（cPDR(1.5h)）表示（cPDR(1.5h)：3.4±1.3%和4.0±2.4% vs. 6.3±1.2%；p<0.01）。包括代谢、治疗和疾病相关变量的多因素分析显示，使用司他夫定、去羟肌苷或扎西他滨进行抗逆转录病毒治疗以及初治状态是MeBT结果（cPDR(1.5h)）降低的最佳预测因素（β=-0.56和-0.50，p<0.05）。CD4细胞计数仅有轻微关联（β=0.15，p<0.05）。包括疾病和治疗持续时间在内的其他变量与MeBT结果均无关联。这些因素解释了MeBT结果39%的变异（p<0.05）。
初治状态和使用d类药物治疗是MeBT结果不佳的最佳预测因素。MeBT可作为一种可行的、非侵入性诊断工具，用于临床评估慢性HIV感染中的肝脏线粒体功能以及早期检测药物诱导的线粒体毒性。
