Browsing by Subject "DRESS"

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    Clinical characteristics of antiepileptic-induced liver injury in patients from the DILIN prospective study
    (Elsevier, 2022) Chalasani, Naga; Bonkovsky, Herbert L.; Stine, Jonathan G.; Gu, Jiezhun; Barnhart, Huiman; Jacobsen, Elin; Björnsson, Einar; Fontana, Robert J.; Kleiner, David E.; Hoofnagle, Jay H.; Drug-Induced Liver Injury Network (DILIN) Study Investigators; Medicine, School of Medicine
    Background & aims: Antiepileptic drugs (AEDs) are a common cause of drug-induced liver injury (DILI). Over the last few decades, several newer AEDs were approved for marketing in the United States, and they are increasingly prescribed for indications other than seizures. Contemporaneous data related to trends and characteristics of AED-related liver injury are sparse. Methods: We report the trends, characteristics, and outcomes of patients with AED-related DILI enrolled into the DILIN Prospective Study between 2004 and 2020. Results: Among 1,711 participants with definite, highly likely, or probable DILI, 66 (3.9%) had AED-related DILI (lamotrigine [n = 18], phenytoin [n = 16], carbamazepine [n = 11], valproate [n = 10], gabapentin [n = 4], and others [n = 7]). The frequency of AED-related liver injury significantly decreased during the study period (from 8.5% of cases during 2004-2007 to 2.6% during 2015-2020, p = 0.01). AEDs other than phenytoin were commonly prescribed for non-seizure indications. Compared to non-AEDs, patients with AED-related liver injury were younger (mean age 38.5 vs. 50.1 years-old, p <0.001) and more likely African American (27% vs. 12%, p = 0.008). DRESS was common with liver injury caused by lamotrigine, phenytoin, and carbamazepine, but not valproate or gabapentin. Liver injury severity was moderate to severe in the majority: 5 died, and 3 underwent orthotopic liver transplantation (OLT). No patient with lamotrigine-related DILI, including 13 with hepatocellular jaundice, died or needed OLT, while 3 out of 16 patients (19%) with phenytoin-related DILI either died or required OLT. Conclusion: The frequency of AED-related liver injury significantly decreased over the last 2 decades in our experience. AED-related liver injury has several distinctive features, including a preponderance in African American patients and those with immunoallergic skin reactions, with outcomes depending on the type of AED involved. Lay summary: Medications used to treat epilepsy may sometimes cause severe liver injury. However, several new medications have been approved over the last 2 decades and they may not be as toxic to the liver as older antiepileptic medications (AEDs). This study shows that overall liver injury due to AEDs is decreasing, likely due to decreasing use of older AEDs. Liver injury due to AEDs appears to be more common in African Americans and is commonly associated with allergic skin reactions.
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    Leflunomide-induced liver injury: Differences in characteristics and outcomes in Indian and US registries
    (Wiley, 2022-06) Devarbhavi, Harshad; Ghabril, Marwan; Barnhart, Huiman; Patil, Mallikarjun; Raj, Sujata; Gu, Jiezhun; Chalasani, Naga; Bonkovsky, Herbert L.; Medicine, School of Medicine
    Background: 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. Methods: 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. Results: 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 Conclusion: 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.