Kumar Ramesh, Kumar Abhishek, Patel Rishabh, Prakash Sabbu Surya, Kumar Sudhir, Surya Himanshu, Marrapu Sudheer
Department of Gastroenterology, All India Institute of Medical Sciences, 4T Floor, OPD Block, Patna, 801 507, India.
Indian J Gastroenterol. 2025 Feb;44(1):35-46. doi: 10.1007/s12664-024-01643-w. Epub 2024 Sep 3.
Antituberculosis drug-induced liver injury (ATDILI) is a significant problem of tuberculosis treatment. This systematic review and meta‑analysis aimed at evaluating the incidence and risk factors of ATDILI in adult patients with tuberculosis in India.
Five electronic databases were searched comprehensively for studies on Indian adult patients with tuberculosis investigating the incidence and/or risk factors of ATDILI. The relevant data was pooled in a random or fixed-effect model to calculate the pooled incidence with a 95% confidence interval (CI), standardized mean difference (MD) or odds ratio (OR).
Following the screening of 3221 records, 43 studies with 12,041 tuberculosis patients were finally included. Based on the random effect model, the pooled incidence of ATDILI was 12.6% (95% CI, 9.9-15.3%, p < 0.001, I = 95.1%). The pooled incidence was higher in patients with daily treatment regimen compared to the thrice weekly regimen (16.5% vs. 3.5%). The concurrent hepatitis B or C infection, alcohol consumption and underlying chronic liver disease were associated with high incidence of ATDILI. The pooled incidence of acute liver failure (ALF) among ATDILI patients was 6.78% (95% CI 3.9-9.5%). Female gender (OR 1.24), older age (MD 0.26), lean body mass index (OR 3.8), hypoalbuminemia (OR 3.09), N-acetyltransferase slow acetylator genotypes (OR 2.3) and glutathione S-transferases M null mutation (OR 1.6) were found to be associated with an increased risk of ATDILI. The pooled mortality rate of ATDILI patients was 1.72% (95% CI 0.4-3.0%) overall and 71.8% (95% CI 49.3-94.2%) in case of ALF.
Overall, 12.6% patients of tuberculosis in India developed ATDILI when combination of first-line antituberculosis drugs was used. An average of 7% of ATDILI patients progressed to ALF which had a high mortality rate. Older age, female, poor nutritional status and some genetic polymorphisms were identified as significant risk factors.
抗结核药物性肝损伤（ATDILI）是结核病治疗中的一个重大问题。本系统评价和荟萃分析旨在评估印度成年结核病患者中ATDILI的发生率及危险因素。
全面检索五个电子数据库，查找关于印度成年结核病患者ATDILI发生率和/或危险因素的研究。将相关数据合并到随机或固定效应模型中，以计算合并发生率及95%置信区间（CI）、标准化均数差（MD）或比值比（OR）。
在筛选的3221条记录中，最终纳入了43项研究，共12041例结核病患者。基于随机效应模型，ATDILI的合并发生率为12.6%（95%CI，9.9 - 15.3%，p < 0.001，I = 95.1%）。与每周三次治疗方案相比，每日治疗方案患者的合并发生率更高（16.5%对3.5%）。合并乙肝或丙肝感染、饮酒及潜在慢性肝病与ATDILI的高发生率相关。ATDILI患者中急性肝衰竭（ALF）的合并发生率为6.78%（95%CI 3.9 - 9.5%）。女性（OR 1.24）、年龄较大（MD 0.26）、低体重指数（OR 3.8）、低白蛋白血症（OR 3.09）、N - 乙酰转移酶慢乙酰化基因型（OR 2.3）和谷胱甘肽S - 转移酶M基因缺失突变（OR 1.6）被发现与ATDILI风险增加相关。ATDILI患者的总体合并死亡率为1.72%（95%CI 0.4 - 3.0%），ALF患者的死亡率为71.8%（95%CI 49.3 - 94.2%）。
总体而言，在印度，使用一线抗结核药物联合治疗时，12.6%的结核病患者发生了ATDILI。平均7%的ATDILI患者进展为ALF，且死亡率很高。年龄较大、女性、营养状况差及一些基因多态性被确定为重要危险因素。
