Leflunomide-induced liver injury: Differences in characteristics and outcomes in Indian and US registries.
Leflunomide-induced liver injury: Differences in characteristics and outcomes in Indian and US registries.
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来氟米特诱发的肝损伤：印度和美国登记处的特征和结果差异。
DOI：
10.1111/liv.15189
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发表时间：
2022-06
影响因子：
6.7
通讯作者：
Bonkovsky, Herbert L.
中科院分区：
文献类型：
--
作者：
Devarbhavi, Harshad;Ghabril, Marwan;Barnhart, Huiman;Patil, Mallikarjun;Raj, Sujata;Gu, Jiezhun;Chalasani, Naga;Bonkovsky, Herbert L.
Leflunomide, a disease-modifying anti-rheumatic drug, has been associated with elevations of serum aminotransferases. Herein, we describe the clinical, laboratory features, and outcomes of 17 patients with leflunomide/teriflunomide hepatotoxicity from two large drug-induced liver injury (DILI) registries. Consecutive, adjudicated cases of leflunomide (n=16)-or teriflunomide (n=1)-related DILI from a single center in Bangalore, India and the multicenter US Drug-Induced Liver Injury Network (DILIN) were reviewed. Nine (0.8%) of the 1070 Indian patients and 8 (0.5%) of the 1400 DILIN patients fulfilled criteria for DILI due to leflunomide- or teriflunomide. 89% of the Indian cases were women and all were associated with severe cutaneous adverse reaction (SCAR) and a median drug latency of 49 days, whereas 37.5% of the DILIN cases were female, none exhibited SCAR, and the median drug latency was 166 days. Hepatocellular injury (70%) was more common in women than men (92% vs. 20%) and was associated with younger mean age (41 vs. 59 years), higher peak INR (2.3 vs. 1.2), and higher mortality (58% vs. 0%). Mortality was observed in 6 patients from India (2 of the three with myocarditis) and 1 received liver transplantation from the USA Leflunomide-induced liver injury is predominantly hepatocellular. Leflunomide hepatotoxicity is more likely accompanied by SCAR, a short latency, and a higher mortality in the Indian cohort, with a predominance of females, compared to US DILIN patients. The differences in skin involvement, immunoallergic features, and outcomes among subjects from India vs. the US suggest that genetic or environmental factors are important in the pathogenesis of liver injury. Leflunomide an immunomodulatory drug, widely used in medicine. Although liver injury is known to be associated with leflunomide use, the characteristics of liver injury are surprisingly lacking. Our study across two large registries, the drug-induced liver injury network from USA and another one from India, illustrate the spectrum of liver injury which is often severe with characteristic differences: all patients in the Indian registry exhibited immunoallergic hypersensitivity phenotype with liver injury playing no or contributory role in mortality while none presented with immunoallergic phenotype in the US series with all surviving except one that needed a liver transplantation. The disparate presentations and outcome point to the role of genetic and environmental factors in disease dynamics.
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影响因子：
158.5
作者：
Sabatine, Marc S.;Poh, Kian-Keong;Baggish, Aaron
通讯作者：
Baggish, Aaron
影响因子：
11.5
作者：
Prakash, A;Jarvis, B
通讯作者：
Jarvis, B
影响因子：
37.8
作者：
Kociol, Robb D.;Cooper, Leslie T.;Vardeny, Orly
通讯作者：
Vardeny, Orly
影响因子：
4.2
作者：
Fontana RJ;Watkins PB;Bonkovsky HL;Chalasani N;Davern T;Serrano J;Rochon J;DILIN Study Group
通讯作者：
DILIN Study Group
影响因子：
1.1
作者：
Perez, Pedro;Sze, Wilson;Miller, Joshua
通讯作者：
Miller, Joshua