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Clinical and Liver Biochemistry Phenotypes, and Outcome in 133 Patients with Anti-seizure Drug-Induced Liver Injury
Harshad Devarbhavi1, Aarthi Sridhar2, Sunu Sara Kurien3
1Department of Gastroenterology and Hepatology, St. John's Medical College Hospital, Bangalore, India. harshad.devarbhavi@gmail.com.
Aims And Objective:
Anti-seizure drugs that cause idiosyncratic drug-induced liver injury (DILI) are an important cause of morbidity and mortality in individuals exposed to these drugs. The clinical and demographic characteristics, the liver injury pattern, the outcome, and the agents responsible for hepatotoxicity have not been thoroughly studied. We investigated the aforementioned characteristics in a large cohort of DILI registry patients.
Methods:
Patients with anti-seizure DILI were studied from a large single-center DILI registry between 1998 and 2021. DILI was defined by international working group criteria with at least a probable relation with RUCAM. Immunoallergic features and organ-specific contribution to outcome were investigated.
Results:
Anti-seizure drugs accounted for 133 patients (12.5%) among 1067 patients with idiosyncratic DILI. Compared to other agents, patients with anti-seizure DILI were younger (31 vs 41 years; p = 0.31), were more often females (52% vs 46%; p = 0.19) and had a lower frequency of jaundice (41% vs 59%, p = 0.001), MELD score (14.5 vs 16.5; p = 0.02) and mortality (9.8% vs 15.7%, p = 0.03). Anti-seizure DILI exhibited a greater frequency of hypersensitivity skin rashes (75% vs 22%, p < 0.001), including DRESS (51% vs 13%, p < 0.001) and SJS/TEN (19% vs1%, p < 0.001). A total of 18 different anti-seizure agents were responsible for DILI, largely contributed by carbamazepine (n = 36), phenytoin (n = 71), phenobarbitone (n = 8) and valproate (n = 14) which accounted for 89% of cases and 85% of 13 deaths.
Conclusions:
Anti-seizure DILI are caused predominantly by first generation drugs. Newer agents account for < 10% of cases. Hypersensitivity reaction is the most common phenotypic presentation. Both severity and mortality are lower with anti-seizure DILI.
Insights
Anti-seizure drug-induced liver injury (DILI) is often linked to hypersensitivity reactions and primarily caused by older medications. While less severe than other DILI causes, it still warrants careful monitoring in patients.
Area of Science:
- Hepatology
- Clinical Pharmacology
- Immunology
Background:
- Idiosyncratic drug-induced liver injury (DILI) from anti-seizure medications poses significant health risks.
- Comprehensive studies on the clinical and demographic profiles, injury patterns, and outcomes of anti-seizure DILI are limited.
Purpose of the Study:
- To investigate the clinical and demographic characteristics of patients experiencing anti-seizure DILI.
- To analyze the specific liver injury patterns, outcomes, and causative agents in a large DILI registry cohort.
Main Methods:
- A retrospective analysis of patients diagnosed with anti-seizure DILI between 1998 and 2021 from a single-center DILI registry.
- DILI diagnosis adherence to international working group criteria with RUCAM assessment; investigation of immunoallergic features and organ involvement.
Main Results:
- Anti-seizure drugs caused 12.5% of idiosyncratic DILI cases (133/1067 patients).
- Patients with anti-seizure DILI were younger, predominantly female, and showed lower rates of jaundice, MELD scores, and mortality compared to other DILI causes.
- Hypersensitivity reactions, including DRESS and SJS/TEN, were more frequent in anti-seizure DILI. Carbamazepine and phenytoin were the leading causative agents.
Conclusions:
- First-generation anti-seizure drugs are the primary culprits of DILI, with newer agents implicated in less than 10% of cases.
- Hypersensitivity reactions are the hallmark presentation of anti-seizure DILI.
- Anti-seizure DILI generally presents with lower severity and mortality rates compared to DILI from other drug classes.
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