Department of Medicine, All India Institute of Medical Sciences, New Delhi, India.
Indian J Med Res. 2010 Jul;132:81-6.
BACKGROUND & OBJECTIVES: Antituberculosis (anti-TB) drug induced hepatotoxicity (DIH) is the most common side effect leading to interruption of therapy. Wide variations have been found in the reported incidence of hepatotoxicity during short-course chemotherapy. Several risk factors for hepatotoxicity have been suggested in previous studies. We undertook a prospective case-control study to assess the role of these putative risk factors in the development of DIH in patients receiving anti-TB treatment.
One hundred and seventy five consecutive cases with a diagnosis of anti-TB DIH were compared with 428 consecutive controls who took anti-TB drugs for the full duration of chemotherapy without clinical or biochemical evidence of hepatitis. Cases positive for markers of acute viral hepatitis were carefully excluded. Cases and controls were compared with respect to age, sex, site of tuberculosis, radiological extent of disease on chest radiograph, body mass index (BMI), mid-arm circumference (MAC) and liver function at baseline which included serum bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), serum total protein and serum albumin.
Univariate logistic regression revealed that the risk of developing DIH was greater in older patients. Significantly greater percentage of cases had extrapulmonary tuberculosis (TB) (P<0.01). Also, a significantly higher percentage of cases had moderate to far advanced disease severity on chest radiograph (P<0.01). On multivariate logistic regression, the adjusted odds were significant (P<0.01) for age>35 yr, MAC<20 cm and hypoalbuminaemia (albumin<3.5 g/dl).
INTERPRETATION & CONCLUSIONS: Older age, poor nutritional status including baseline hypoalbuminaemia were independent predictors of occurrence of anti-TB DIH. Clinicians should be vigilant for occurrence of hepatotoxicity in this high risk group.
抗结核（anti-TB）药物性肝损伤（DIH）是导致治疗中断的最常见的副作用。在短程化疗期间，肝毒性的报告发生率存在很大差异。先前的研究提出了一些肝毒性的危险因素。我们进行了一项前瞻性病例对照研究，以评估这些假定的危险因素在接受抗结核治疗的患者中发展为 DIH 的作用。
将 175 例连续诊断为抗结核 DIH 的病例与 428 例连续接受抗结核药物治疗但无临床或生化证据表明有肝炎的对照进行比较。仔细排除了急性病毒性肝炎标志物阳性的病例。对病例和对照组的年龄、性别、结核部位、胸部 X 线疾病的放射学范围、体重指数（BMI）、上臂中部周长（MAC）以及基线时的肝功能（包括血清胆红素、天门冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、碱性磷酸酶（ALP）、血清总蛋白和血清白蛋白）进行比较。
单变量逻辑回归显示，年龄较大的患者发生 DIH 的风险更高。病例组中患有肺外结核（TB）的比例显著更高（P<0.01）。此外，病例组中有更多的患者在胸部 X 线上表现为中度至严重疾病（P<0.01）。在多变量逻辑回归中，年龄>35 岁、MAC<20cm 和低白蛋白血症（白蛋白<3.5g/dl）的调整比值均有显著意义（P<0.01）。
年龄较大、包括基线时低白蛋白血症在内的营养状况较差是发生抗结核 DIH 的独立预测因素。临床医生应警惕该高危人群发生肝毒性。
