Døssing M, Wilcke J T, Askgaard D S, Nybo B
Medical Department P, Bispebjerg Hospital, Copenhagen, Denmark.
Tuber Lung Dis. 1996 Aug;77(4):335-40. doi: 10.1016/s0962-8479(96)90098-2.
Bispebjerg Hospital, Department of Pulmonary Medicine, tuberculosis referral center for the Municipality of Copenhagen.
To evaluate routine procedure for the management of liver injury during antituberculosis treatment.
From 1983-1993, 765 patients for whom we could trace 752 files (98%) were treated at our ward with standard Danish treatment for tuberculosis. From 1983-1986 they received a three-drug (9-month) regimen and from 1986-1993 a four-drug (6-month) regimen consisting of isoniazid, rifampicin, ethambutol + pyrazinamide. Data from a retrospective chart review.
An increase in aspartate aminotransferase (AST) of more than twice the upper limit of normal (ULN) was recorded in 127 patients (16%). 66 had elevated AST before treatment; most of these were men with a daily alcohol consumption in excess of 60 g. In the remaining 61 patients (8%) AST increased during antituberculosis treatment. 30 of these patients were excessive alcohol consumers, and seven had alcoholic liver cirrhosis. Despite an increase in AST of median 6 x ULN (range 2-25 x ULN), it was possible to continue treatment in 31 (15 excessive alcohol consumers) or reintroduce it fully in 14 (12 excessive alcohol consumers). Only 16 patients (2%), including 11 women with no daily alcohol consumption, needed a modified regimen. These patients were older (P < 0.05), seven were jaundiced, and one had alcoholic liver cirrhosis. Hepatotoxicity was confirmed by challenge with pyrazinamide (n = 7), isoniazid (n = 6) and combined isoniazid/rifampicin (n = 1). No deaths were caused by hepatotoxicity.
In spite of an increase in AST levels to approximately 6 x ULN during antituberculosis treatment, the drugs can be continued or reintroduced in full in most cases. Risk factors of hepatotoxicity included old age, female sex and extensive tuberculosis, and not alcohol consumption. Overall, hepatotoxicity during antituberculosis treatment can be monitored and managed easily.
比斯佩比约格医院，肺科，哥本哈根市结核病转诊中心。
评估抗结核治疗期间肝损伤管理的常规程序。
1983年至1993年，我们病房对765例患者采用丹麦标准抗结核治疗，其中752例患者的病历可追溯（98%）。1983年至1986年，他们接受三联（9个月）治疗方案，1986年至1993年接受四联（6个月）治疗方案，包括异烟肼、利福平、乙胺丁醇和吡嗪酰胺。数据来自回顾性病历审查。
127例患者（16%）的天门冬氨酸氨基转移酶（AST）升高超过正常上限（ULN）的两倍。66例患者治疗前AST升高；其中大多数为每日饮酒量超过60克的男性。其余61例患者（8%）在抗结核治疗期间AST升高。这些患者中有30例饮酒过量，7例患有酒精性肝硬化。尽管AST中位数升高至6倍ULN（范围为2至25倍ULN），但仍有31例（15例饮酒过量者）能够继续治疗，14例（12例饮酒过量者）能够完全重新开始治疗。只有16例患者（2%），包括11例无每日饮酒习惯的女性，需要调整治疗方案。这些患者年龄较大（P<0.05），7例黄疸，1例患有酒精性肝硬化。通过吡嗪酰胺激发试验（n=7）、异烟肼激发试验（n=6）和异烟肼/利福平联合激发试验（n=1）证实了肝毒性。无肝毒性导致死亡。
尽管抗结核治疗期间AST水平升高至约6倍ULN，但大多数情况下仍可继续或完全重新使用这些药物。肝毒性的危险因素包括老年、女性和广泛的结核病，而非饮酒。总体而言，抗结核治疗期间的肝毒性易于监测和管理。
