Pettersson Jonas, Hindorf Ulf, Persson Paula, Bengtsson Thomas, Malmqvist Ulf, Werkström Viktoria, Ekelund Mats
AstraZeneca R&D Lund, Lund, Sweden.
Br J Clin Pharmacol. 2008 Feb;65(2):253-9. doi: 10.1111/j.1365-2125.2007.03001.x. Epub 2007 Aug 31.
The occurrence of idiosyncratic drug hepatotoxicity is a major problem in all phases of clinical drug development and the leading cause of postmarketing warnings and withdrawals. Physical exercise can result in transient elevations of liver function tests. There is no consensus in the literature on which forms of exercise may cause changes in liver function tests and to what extent.
Weightlifting results in profound increases in liver function tests in healthy men used to moderate physical activity, not including weightlifting. Liver function tests are significantly increased for at least 7 days after weightlifting. It is important to impose relevant restrictions on heavy muscular exercise prior to and during clinical studies.
To investigate the effect of intensive muscular exercise (weightlifting) on clinical chemistry parameters reflecting liver function in healthy men.
Fifteen healthy men, used to moderate physical activity not including weightlifting, performed an 1 h long weightlifting programme. Blood was sampled for clinical chemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LD), gamma-glutamyl transferase (gamma GT), alkaline phosphatase (ALP), bilirubin, creatine kinase (CK) and myoglobin] at repeated intervals during 7 days postexercise and at a follow-up examination 10-12 days postexercise.
Five out of eight studied clinical chemistry parameters (AST, ALT, LD, CK and myoglobin) increased significantly after exercise (P < 0.01) and remained increased for at least 7 days postexercise. Bilirubin, gamma GT and ALP remained within the normal range.
The liver function parameters, AST and ALT, were significantly increased for at least 7 days after the exercise. In addition, LD and, in particular, CK and myoglobin showed highly elevated levels. These findings highlight the importance of imposing restrictions on weightlifting prior to and during clinical studies. Intensive muscular exercise, e.g. weightlifting, should also be considered as a cause of asymptomatic elevations of liver function tests in daily clinical practice.
特异质性药物肝毒性的发生是临床药物研发各阶段的一个主要问题，也是上市后发出警告和撤市的主要原因。体育锻炼可导致肝功能检查结果短暂升高。对于哪些形式的运动会引起肝功能检查结果变化以及变化程度如何，文献中尚无共识。
对于习惯适度体育活动（不包括举重）的健康男性，举重会导致肝功能检查结果大幅升高。举重后至少7天内，肝功能检查结果会显著升高。在临床研究之前和期间，对高强度肌肉运动施加相关限制很重要。
研究高强度肌肉运动（举重）对健康男性反映肝功能的临床化学参数的影响。
15名习惯适度体育活动（不包括举重）的健康男性进行了1小时的举重项目。在运动后7天内的不同时间点以及运动后10 - 12天的随访检查时，采集血液样本检测临床化学参数[天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、乳酸脱氢酶（LD）、γ-谷氨酰转移酶（γGT）、碱性磷酸酶（ALP）、胆红素、肌酸激酶（CK）和肌红蛋白]。
所研究的八项临床化学参数中的五项（AST、ALT、LD、CK和肌红蛋白）在运动后显著升高（P < 0.01），并且在运动后至少7天内一直保持升高。胆红素、γGT和ALP仍在正常范围内。
运动后至少7天内，肝功能参数AST和ALT显著升高。此外，LD，尤其是CK和肌红蛋白水平大幅升高。这些发现凸显了在临床研究之前和期间对举重施加限制的重要性。在日常临床实践中，高强度肌肉运动，如举重，也应被视为肝功能检查结果无症状升高的一个原因。
