Drug-Induced Liver Injury During Treatment With Tocilizumab: A Case Report of an Atypical Pattern Lesion.

IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Louis-Edmond Barbaro, Nouha Ben Othman, Delphine Viard, Fanny Rocher, Elliot Ewig, Raja Mroue, Claire Amigues, Alexandre O Gérard
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Abstract

Tocilizumab is an interleukin-6 (IL-6) receptor antagonist indicated for various rheumatologic conditions. While hepatotoxicity is a recognized adverse effect, it predominantly manifests as hepatocellular injury. We report a rare case of drug-induced liver injury (DILI) presenting with a cholestatic pattern and cholangitis features in a 75-year-old patient treated for giant cell arteritis. Following the third tocilizumab infusion, the patient developed jaundice and abdominal pain. Laboratory investigations revealed a cholestatic pattern of liver injury (ALT/ALP (R) ratio ≤ 2) with marked cholestasis. Imaging findings raised suspicion for cholangitis. After ruling out infectious, autoimmune, and metabolic aetiologies, a liver biopsy confirmed neutrophilic cholangitis and marked intrahepatic and sinusoidal cholestasis. Drug discontinuation, along with ursodeoxycholic acid treatment, led to clinical and biochemical resolution. This case is notable as tocilizumab-induced liver injury rarely presents with cholangitic features. The pathophysiology may involve the disruption of IL-6 signaling, which plays a pivotal role in maintaining biliary epithelial integrity. Clinicians should be vigilant for this atypical cholestatic presentation to ensure prompt drug withdrawal.

托珠单抗治疗期间药物性肝损伤:一例非典型病变报告。
Tocilizumab是一种白细胞介素-6 (IL-6)受体拮抗剂,适用于各种风湿病。虽然肝毒性是公认的不良反应,但主要表现为肝细胞损伤。我们报告一个罕见的病例药物性肝损伤(DILI)表现为胆汁淤积模式和胆管炎特征在一个75岁的病人治疗巨细胞动脉炎。在第三次托珠单抗输注后,患者出现黄疸和腹痛。实验室检查显示肝损伤呈胆汁淤积型(ALT/ALP (R)比值≤2),伴有明显的胆汁淤积。影像学表现提示胆管炎的怀疑。在排除了感染性、自身免疫性和代谢性病因后,肝活检证实中性粒细胞胆管炎和明显的肝内和窦内胆汁淤积。停药,以及熊去氧胆酸治疗,导致临床和生化解决。该病例值得注意,因为托珠单抗引起的肝损伤很少表现为胆管病变。病理生理可能涉及IL-6信号的破坏,IL-6信号在维持胆道上皮完整性中起关键作用。临床医生应警惕这种不典型的胆汁淤积表现,以确保及时停药。
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来源期刊
Pharmacology Research & Perspectives
Pharmacology Research & Perspectives Pharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics
CiteScore
5.30
自引率
3.80%
发文量
120
审稿时长
20 weeks
期刊介绍: PR&P is jointly published by the American Society for Pharmacology and Experimental Therapeutics (ASPET), the British Pharmacological Society (BPS), and Wiley. PR&P is a bi-monthly open access journal that publishes a range of article types, including: target validation (preclinical papers that show a hypothesis is incorrect or papers on drugs that have failed in early clinical development); drug discovery reviews (strategy, hypotheses, and data resulting in a successful therapeutic drug); frontiers in translational medicine (drug and target validation for an unmet therapeutic need); pharmacological hypotheses (reviews that are oriented to inform a novel hypothesis); and replication studies (work that refutes key findings [failed replication] and work that validates key findings). PR&P publishes papers submitted directly to the journal and those referred from the journals of ASPET and the BPS
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