Khan Adeel Ahmad, Ata Fateen, Aziz Afia, Elamin Hana, Shahzad Aamir, Yousaf Zohaib, Donato Anthony
Department of Endocrinology, Hamad Medical Corporation, 3050, Doha, Qatar.
Department of Internal Medicine, Hamad Medical Corporation, 3050, Doha, Qatar.
J Endocr Soc. 2023 Oct 27;8(1):bvad133. doi: 10.1210/jendso/bvad133. eCollection 2023 Dec 1.
Antithyroid drugs (ATDs) are the cornerstone of hyperthyroidism management. Hepatotoxicity due to ATDs can range from mild transaminase elevation to liver transplantation requirement and mortality.
The primary objective of the systematic review was to assess the clinical characteristics and outcomes of patients with drug induced liver injury (DILI) due to ATDs.
We conducted a systematic review of PUBMED, SCOPUS, and EMBASE on characteristics and outcomes of adults (>18 years) with DILI due to ATDs. We defined DILI as bilirubin ≥2.5 mg/dL or international normalized ratio >1.5 with any rise in alanine aminotransferase (ALT), aminotransferase (AST), or alkaline phosphatase (ALP), or an elevation of ALT or AST >5 times or ALP >2 times the upper limit of normal without jaundice/coagulopathy.
The review included 100 articles describing 271 patients; 148 (70.8%) were female (N = 209). Mean age was 42.9 ± 17.2 years. Graves' disease was the most common indication for ATDs. Carbimazole/methimazole (CBM/MMI) was the most common offending agent (55.7%). DILI pattern was hepatocellular in 41.8%, cholestatic in 41.3%, and mixed in 16.9%. Outcomes included death in 11.8%, liver transplantation in 6.4%, partial improvement in 2.2%, and complete resolution in 79.6% with a median time (IQR) to resolution of 45 (20-90) days. Patients in the propylthiouracil (PTU) group had higher initial bilirubin, initial AST, initial ALT, peak ALT, peak AST, severe and fatal DILI, liver transplantation, and mortality than CBM/MMI. Rechallenge of antithyroid medication was infrequently reported (n = 16) but was successful in 75%.
DILI due to ATDs can present with different patterns and should prompt immediate drug discontinuation. Referral to a hepatologist should be considered if severe as transplantation is sometimes required. PTU-induced DILI may have worse outcomes than CBM/MMI.
抗甲状腺药物（ATD）是甲亢治疗的基石。ATD所致肝毒性的范围可从轻度转氨酶升高到需要肝移植甚至死亡。
本系统评价的主要目的是评估因ATD导致药物性肝损伤（DILI）患者的临床特征及转归。
我们对PUBMED、SCOPUS和EMBASE进行了系统评价，以了解成年（>18岁）ATD所致DILI患者的特征及转归。我们将DILI定义为胆红素≥2.5mg/dL或国际标准化比值>1.5，同时丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）或碱性磷酸酶（ALP）有任何升高，或在无黄疸/凝血障碍情况下ALT或AST升高>正常上限5倍或ALP升高>正常上限2倍。
该评价纳入了100篇描述271例患者的文章；148例（70.8%）为女性（N = 209）。平均年龄为42.9±17.2岁。格雷夫斯病是使用ATD最常见的适应证。卡比马唑/甲巯咪唑（CBM/MMI）是最常见的致病药物（55.7%）。DILI类型肝细胞型占41.8%，胆汁淤积型占41.3%，混合型占16.9%。转归包括11.8%死亡，6.4%接受肝移植，2.2%部分改善，79.6%完全缓解，缓解的中位时间（IQR）为45（20 - 90）天。丙硫氧嘧啶（PTU）组患者的初始胆红素、初始AST、初始ALT、峰值ALT、峰值AST、严重及致命性DILI、肝移植及死亡率均高于CBM/MMI组。再次使用抗甲状腺药物的报道较少（n = 16），但成功率为75%。
ATD所致DILI可呈现不同类型，应立即停药。如果病情严重，由于有时需要进行肝移植，应考虑转诊至肝病专家处。PTU所致DILI的转归可能比CBM/MMI更差。
