Bessone Fernando, Hernandez Nelia, Medina-Caliz Inmaculada, García-Cortés Miren, Schinoni María I, Mendizabal Manuel, Chiodi Daniela, Nunes Vinicius, Ridruejo Ezequiel, Pazos Ximena, Santos Genario, Fassio Eduardo, Parana Raymundo, Reggiardo Virginia, Tanno Hugo, Sanchez Adriana, Tanno Federico, Montes Pedro, Tagle Martin, Arrese Marco, Brahm Javier, Girala Marcos, Lizarzabal M Isabel, Carrera Enrique, Zerega Alina, Bianchi Carla, Reyes Laura, Arnedillo Daina, Cordone Antonella, Gualano Gisela, Jaureguizahar Fernanda, Rifrani Gabriel, Robles-Díaz Mercedes, Ortega-Alonso Aida, Pinazo-Bandera José M, Stephens Camilla, Sanabria-Cabrera Judith, Bonilla-Toyos Elvira, Niu Hao, Alvarez-Alvarez Ismael, Lucena M Isabel, Andrade Raul J
Hospital Provincial del Centenario, Facultad de Medicina, Universidad Nacional de Rosario, Rosario, Argentina.
Hospital de Clínicas, Universidad de la República, Montevideo, Uruguay.
Clin Gastroenterol Hepatol. 2025 Jan;23(1):89-102. doi: 10.1016/j.cgh.2024.06.030. Epub 2024 Jul 9.
BACKGROUND & AIMS: Latin America is a region of great interest for studying the clinical presentation of idiosyncratic drug-induced liver injury (DILI). A comprehensive analysis of patients enrolled into the LATINDILI Network over a decade is presented.
Demographics, clinical presentation, histological findings and outcome of prospectively recruited DILI cases in the LATINDILI Network were analyzed. Suspected culprit drugs were classified according to the Anatomical Therapeutic Chemical classification. Causality was assessed using the Roussel Uclaf Causality Assessment Method (RUCAM) scale.
Overall, 468 idiosyncratic DILI cases were analyzed (62% women; mean age, 49 years). Hepatocellular injury predominated (62%); jaundice was present in 60% of patients, and 42% were hospitalized. Of the cases, 4.1% had a fatal outcome, and 24 patients (12%) developed chronic DILI. The most common drug classes were systemic anti-infectives (31%), musculoskeletal agents (12%), antineoplastic and immunomodulating agents (11%), and herbal and dietary supplements (9%). Notably, none of the patients with DILI due to antibacterials or immunosuppressants had a fatal outcome. In fact, Hy's law showed to have drug-specific predictive value, with anti-tuberculosis drugs, nimesulide, and herbal and dietary supplements associated with the worst outcome, whereas DILI caused by amoxicillin-clavulanate, nitrofurantoin, and diclofenac, which fulfilled Hy's law, did not have a fatal outcome.
Features of DILI in Latin America are comparable to other prospective registries. However, the pattern of drugs responsible for DILI differs. An increasing incidence of herbal and dietary supplements, with high mortality rate, and likewise, nimesulide and nitrofurantoin, was noted. Thus, public health policies should raise awareness of the potential adverse effects of these compounds.
拉丁美洲是研究特异质性药物性肝损伤(DILI)临床表现的一个极具研究价值的地区。本文对拉丁美洲药物性肝损伤网络(LATINDILI Network)十年来招募的患者进行了全面分析。
分析了LATINDILI网络中前瞻性招募的DILI病例的人口统计学特征、临床表现、组织学检查结果及预后。根据解剖学治疗学化学分类对可疑致病药物进行分类。使用乌普萨拉监测中心因果关系评估方法(RUCAM)量表评估因果关系。
总体而言,共分析了468例特异质性DILI病例(62%为女性;平均年龄49岁)。肝细胞损伤最为常见(62%);60%的患者出现黄疸,42%的患者住院治疗。其中,4.1%的病例预后不良,24例患者(12%)发展为慢性DILI。最常见的药物类别为全身用抗感染药(31%)、肌肉骨骼用药(12%)、抗肿瘤和免疫调节药(11%)以及草药和膳食补充剂(9%)。值得注意的是,因抗菌药物或免疫抑制剂导致DILI的患者均无不良预后。事实上,海氏法则显示出药物特异性预测价值,抗结核药物、尼美舒利以及草药和膳食补充剂与最差的预后相关,而符合海氏法则的阿莫西林-克拉维酸、呋喃妥因和双氯芬酸所致DILI并无不良预后。
拉丁美洲DILI的特征与其他前瞻性登记研究相似。然而,导致DILI的药物模式有所不同。草药和膳食补充剂的发病率呈上升趋势,且死亡率较高,同样,尼美舒利和呋喃妥因也是如此。因此,公共卫生政策应提高对这些化合物潜在不良反应的认识。