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血浆置换治疗达可替尼引起的严重肝内胆汁淤积症:一例报告。

Plasma exchange treats severe intrahepatic cholestasis caused by dacomitinib: A case report.

机构信息

Department of Hepatology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.

出版信息

Medicine (Baltimore). 2022 Jul 8;101(27):e29629. doi: 10.1097/MD.0000000000029629.

Abstract

RATIONALE

Dacomitinib-induced liver injury is often manifested by mild elevations of transaminases and bilirubin, and severe intrahepatic cholestasis caused by dacomitinib for simultaneous taking orally cytochrome P450 2D6 (CYP2D6) competitive substrates has been rarely reported.

PATIENT CONCERNS

The patient was a 69-year-old woman with non-small cell lung cancer (NSCLC) who was prescribed oral dacomitinib for a month; she was given oral loratadine due to "allergic rhinitis" and metoprolol extended action tablets due to "tachycardia" separately for a few days during the course of dacomitinib treatment. The patient developed liver damage, increased fatigue, yellow urine, and pruritus, with significantly elevated serum levels of bilirubin and glutamyltranspetidase.

DIAGNOSIS

Intrahepatic cholestasis, drug-induced liver injury, and NSCLC.

INTERVENTIONS

After admission, the patient was prescribed adenosylmethionine, acetylcysteine, ursodeoxycholic acid capsule, methylprednisolone and fenofibrate for a month, with progressive elevation of liver biochemical parameters. Through drug enzyme gene assays in the liver tissue after percutaneous liver biopsy, we found both CYP2D6*10/*10 and ATP-binding cassette subfamily B member 1 GG variants (rs1045642) positive. After the poor response to the conventional medication, the patient underwent plasma exchange.

OUTCOMES

The patient was discharged after her liver parameters improved; the parameters remained normal at several follow-up visits, and she renewed the NSCLC regimens without dacomitinib after being evaluated by oncologists.

LESSONS

Dacomitinib can induce severe intrahepatic cholestasis. It is considered that patients with intermediate metabolic CYP2D6 are susceptible to drug-induced liver injury caused by dacomitinib; plasma exchange may be an effective treatment.

摘要

背景

达可替尼引起的肝损伤常表现为转氨酶和胆红素轻度升高,同时口服细胞色素 P450 2D6(CYP2D6)竞争性底物引起严重的肝内胆汁淤积症则鲜有报道。

病例介绍

患者为 69 岁女性,患有非小细胞肺癌(NSCLC),接受达可替尼治疗 1 个月;在达可替尼治疗过程中,因“过敏性鼻炎”分别服用了口服氯雷他定,因“心动过速”服用了琥珀酸美托洛尔缓释片数天,后出现肝损伤,出现疲劳加重、尿色发黄和瘙痒,胆红素和谷氨酰转肽酶显著升高。

诊断

肝内胆汁淤积症、药物性肝损伤和 NSCLC。

干预措施

入院后,患者接受了腺苷蛋氨酸、乙酰半胱氨酸、熊去氧胆酸胶囊、甲泼尼龙和非诺贝特治疗 1 个月,肝生化参数逐渐升高。通过经皮肝活检肝组织中的药物酶基因检测,发现 CYP2D6*10/*10 和三磷酸腺苷结合盒亚家族 B 成员 1 GG 变异体(rs1045642)均为阳性。常规药物治疗反应不佳后,患者接受了血浆置换。

结果

患者肝参数改善后出院;在几次随访中,肝参数保持正常,经肿瘤专家评估后,她在不使用达可替尼的情况下,更新了 NSCLC 治疗方案。

结论

达可替尼可引起严重的肝内胆汁淤积症。考虑到中间代谢 CYP2D6 的患者易发生达可替尼引起的药物性肝损伤;血浆置换可能是一种有效的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b37/9259143/384ace6ee45f/medi-101-e29629-g001.jpg

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