Department of Respiratory Medicine, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, People's Republic of China.
Department of Respiratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian, People's Republic of China.
Int Immunopharmacol. 2020 Jun;83:106537. doi: 10.1016/j.intimp.2020.106537. Epub 2020 May 1.
Immune checkpoint inhibitors (ICIs) have been identified as validated medications in non-small cell lung cancer (NSCLC). However, they are often associated with immune-related adverse events (irAEs) including liver dysfunction. Therefore, we conducted a systematic review of the literature and performed a meta-analysis to ascertain overall incidence and risk of immune mediated liver dysfunction in NSCLC patients.
PubMed, the Cochrane Library, Embase and ClinicalTrials.gov (http://clinicaltrials.gov/) were searched from inception to December 2019. Studies regarding all grade (1-5), high grade (3-5) hepatitis and ALT or AST elevation were included.
A total of 11 clinical trials including 7086 patients were selected for further assessment. The overall incidence of ALT elevation, AST elevation and hepatitis for the application of ICIs was 6.18%, 4.99% and 1.09%, respectively. Compared with chemotherapy group, treatment with ICIs had a significantly higher risk of all grade (RR: 7.27, p = 0.001) and high grade (RR: 6.70, p = 0.003) hepatitis. When ICIs combined with chemotherapy, the relative risk of all grade hepatitis was higher than monotherapy group (RR: 7.89, p = 0.044 vs RR: 6.94, p = 0.008).
The application of ICIs could result in a higher incidence and relative risk of all grade immune-induced liver dysfunction. Moreover, immunotherapy combined with chemotherapy may also increase relative risk of all grade hepatic AEs when compared with monotherapy. Prompt recognition and proper administration is required for clinicians to prevent potentially hepatic deterioration.
免疫检查点抑制剂（ICI）已被确定为非小细胞肺癌（NSCLC）的有效药物。然而，它们常伴有免疫相关不良反应（irAEs），包括肝功能障碍。因此，我们进行了系统的文献回顾，并进行了荟萃分析，以确定 NSCLC 患者免疫介导的肝功能障碍的总发生率和风险。
从建库到 2019 年 12 月，我们在 PubMed、Cochrane 图书馆、Embase 和 ClinicalTrials.gov（http://clinicaltrials.gov/）上进行了检索。纳入所有等级（1-5 级）、高等级（3-5 级）肝炎和 ALT 或 AST 升高的研究。
共纳入 11 项临床试验，包括 7086 例患者进行进一步评估。ICI 应用的 ALT 升高、AST 升高和肝炎的总发生率分别为 6.18%、4.99%和 1.09%。与化疗组相比，ICI 治疗有更高的所有等级（RR：7.27，p=0.001）和高等级（RR：6.70，p=0.003）肝炎的风险。ICI 联合化疗时，所有等级肝炎的相对风险高于单药组（RR：7.89，p=0.044 比 RR：6.94，p=0.008）。
ICI 的应用可能导致更高的发生率和所有等级免疫诱导的肝功能障碍的相对风险。此外，与单药治疗相比，免疫治疗联合化疗可能也会增加所有等级肝不良事件的相对风险。临床医生需要及时识别并正确处理，以防止潜在的肝功能恶化。
