Faculty of MedicineUniversity of IcelandReykjavikIceland.
Division of Gastroenterology and HepatologyDepartment of Internal MedicineThe National University Hospital of IcelandReykjavikIceland.
Hepatol Commun. 2022 Aug;6(8):1895-1909. doi: 10.1002/hep4.1959. Epub 2022 May 21.
Nitrofurantoin, minocycline, methyldopa and infliximab, have been found to induce autoimmune-like hepatitis (DI-AILH). Evidence for other drugs and herbal and dietary supplements (HDS) is unclear. The aims of the study were to establish criteria to define and review the published evidence of suspected DI-AILH. Search was undertaken in Pubmed using search terms "drug-induced liver injury," "autoimmune hepatitis," and "drug-induced autoimmune hepatitis." DI-AILH was defined as (1) drug as a potential trigger of liver injury with autoimmune features and histological findings compatible with AIH; (2) no or incomplete recovery or worsening of liver tests after discontinuation of the drug; (3) corticosteroids requirement or spontaneous recovery; (4) follow-up without immunosuppression (IS) and no relapse of AIH at least 6 months after discontinuation of IS; and (5) drugs potentially inducing AILH with a chronic course. Cases fulfilling the first four criteria were considered probable DI-AILH with three possible DI-AILH. A total of 186 case reports were identified for conventional drugs (n = 148; females 79%; latency 2.6 months) and HDS (n = 38; females 50%). The most commonly reported agents of DI-AILH were interferons (n = 37), statins (n = 24), methylprednisolone (MPS) (n = 16), adalimumab (n = 10), imatinib (n = 8), and diclofenac (n = 7). Tinospora cordifolia and Khat were the only HDS with probable DI-AILH cases. No relapses of AIH were observed when IS was stopped after interferons, imatinib, diclofenac, and methylprednisolone. Conclusion: Beyond well-recognized nitrofurantoin, methyldopa, hydralazine, minocycline, and infliximab as causes of DI-AILH, interferons, imatinib, adalimumab, and MPS were the best-documented agents leading to probable DI-AILH. Khat and Tinospora cordifolia were the only HDS found to be able to induce DI-AILH. Long-term immunosuppression appears to be rarely required in patients with DI-AILH due to these drugs.
硝基呋喃妥因、米诺环素、甲基多巴和英夫利昔单抗已被发现可诱导自身免疫样肝炎（DI-AILH）。其他药物、草药和膳食补充剂（HDS）的证据尚不清楚。本研究的目的是建立定义和审查疑似 DI-AILH 已发表证据的标准。在 Pubmed 中使用“药物性肝损伤”、“自身免疫性肝炎”和“药物性自身免疫性肝炎”等术语进行了搜索。DI-AILH 的定义为：（1）药物作为肝损伤的潜在触发因素，具有自身免疫特征和与 AIH 相符的组织学发现；（2）停药后肝功能检查无改善或恶化；（3）需要皮质类固醇或自发性恢复；（4）无免疫抑制（IS）随访，且在停用 IS 至少 6 个月后无 AIH 复发；（5）具有慢性病程的潜在诱导 AILH 的药物。符合前四项标准的病例被认为是可能的 DI-AILH，有三个可能的 DI-AILH。共确定了 186 例常规药物（n=148；女性 79%；潜伏期 2.6 个月）和 HDS（n=38；女性 50%）的病例报告。最常报道的 DI-AILH 药物包括干扰素（n=37）、他汀类药物（n=24）、甲泼尼龙（MPS）（n=16）、阿达木单抗（n=10）、伊马替尼（n=8）和双氯芬酸（n=7）。金果榄和阿拉伯茶是唯一有明确的 DI-AILH 病例的 HDS。干扰素、伊马替尼、双氯芬酸和甲泼尼龙停药后停止 IS 时，未观察到 AIH 复发。结论：除了公认的硝基呋喃妥因、甲基多巴、肼屈嗪、米诺环素和英夫利昔单抗作为 DI-AILH 的原因外，干扰素、伊马替尼、阿达木单抗和 MPS 是导致可能的 DI-AILH 的记录最完善的药物。阿拉伯茶和金果榄是唯一被发现能够诱导 DI-AILH 的 HDS。由于这些药物，DI-AILH 患者很少需要长期免疫抑制。
