1例免疫检查点抑制剂致药物肝损伤患者开展抗结核治疗的药学实践

Pharmaceutical Practice of Anti-Tuberculosis Treatment in One Patient with Drug-Induced Liver Injury Caused by Immune Checkpoint Inhibitors

目的:分析免疫检查点抑制剂致药物肝损伤(drug-induced liver injury,DILI)患者开展抗结核治疗的药学监护过程,为临床合并DILI患者的抗结核治疗提供参考。方法:一食管下段鳞癌术后患者在开展第二疗程化学治疗期间谷丙转氨酶(385.47 U/L)、碱性磷酸酶(456.59 U/L)和总胆红素(156.17μmol/L)水平异常升高,表现为混合型重度肝损伤;其间,患者又出现咳嗽、咳痰和发热(39℃)等症状,并且痰涂片检出抗酸杆菌(+++),结合胸部CT检查结果,考虑为双肺继发性肺结核,临床药物建议启动抗结核治疗。结果:患者出现肝损伤后,临床药师考虑为化疗药物所致(帕博利珠单抗的RUCAM评分为6分,紫杉醇和卡铂分别为5分和4分),但并未停用,而是在异甘草酸镁基础上加用丁二磺酸腺甘蛋氨酸、多烯磷脂酰胆碱、甲泼尼龙进行保肝治疗,然而肝损伤指标仍在加重,遂停用了所有有潜在肝损伤风险的药物;随后在开展抗结核治疗时,考虑到当前患者肝损伤的情况,医生采纳了临床药师的建议,先选用乙胺丁醇、左氧氟沙星、链霉素等肝损伤风险小药物;其间患者肝损伤指标持续改善,遂又加用异烟肼,并将链霉素改为了利奈唑胺;1个月后,患者肝功能正常。结论:面对患者需要在发生重度混合型DILI情况下开展抗结核治疗,临床药师利用自己专业知识,结合相关文献报道,协助医生成功地在治疗患者DILI的同时开展了抗结核治疗,保障了患者的生命健康。

Objective:To analyze the pharmaceutical care process of anti-tuberculosis treatment for the patient with drug-induced liver injury(DILI)caused by immune checkpoint inhibitors,and provide reference for clinical antituberculosis treatment of patients with DILI.Methods:One patient with lower esophageal squamous cell carcinoma after surgery showed abnormally elevated levels of alanine aminotransferase(385.47 U/L),alkaline phosphatase(456.59 U/L)and total bilirubin(156.17μmol/L)during the second course of chemotherapy,with the manifestation of mixed type severe liver injury;during the period,the patient developed symptoms such as cough,expectoration,and fever(39°C),and acid-fast bacilli(+++)were detected in the sputum smear.Combined with the chest CT examination results,the patient was considered to have secondary pulmonary tuberculosis in both lungs.It was recommended to initiate antituberculosis treatment with drugs.Results:After the patient developed liver injury,the clinical pharmacist considered that it was caused by chemotherapy drugs(the RUCAM scores of pembrolizumab,paclitaxel and carboplatin were 6,5,and 4 respectively),but the drugs were not discontinued.The patient received hepatoprotective treatment with adenoglycine butanesulfonate,polyene phosphatidylcholine,and methylprednisolone on the basis of magnesium isoglycyrrhizinate,however,the liver injury indicators continued to worsen,so all drugs with potential risks of liver injury were discontinued;subsequently,when carrying out anti-tuberculosis treatment,taking into account the patient's current liver injury,the doctor adopted the clinical pharmacist's suggestion and used drugs with a low risk of liver injury such as ethambutol,levofloxacin,and streptomycin;during this period,the patient's liver injury indicators kept improving;and then isoniazid was added and streptomycin was changed to linezolid;one month later,the patient's liver function returned to normal.Conclusion:When patients with severe mixed DILI need to carry out anti-tuberculosis treatment,clinical pharmacists should assist doctors in successfully treating patients with DILI and carrying out anti-tuberculosis treatment based on their professional knowledge and relevant literature reports,to ensure the life health of patients.