Health & body · 2022
How did liver injury linked to differ between patients in Indian and US registries?
In this 17-patient review of leflunomide/teriflunomide-related liver injury, the Indian cohort had more women, severe skin reactions in every case versus none in the US cohort, and a shorter median time to injury: 49 versus 166 days. Mortality was also higher in the Indian cohort; six Indian patients died, while one US patient received a liver transplant.
Details
Leflunomide is a disease-modifying antirheumatic drug that has been associated with elevated serum aminotransferases. This study described the clinical features, laboratory findings and outcomes of 17 patients with leflunomide/teriflunomide hepatotoxicity from two large drug-induced liver injury (DILI) registries.
The researchers reviewed consecutive, adjudicated DILI cases related to leflunomide (16 patients) or teriflunomide (1 patient), drawing on a single centre in Bangalore, India, and the multicentre US Drug-Induced Liver Injury Network (DILIN).
Of 1070 patients in the Indian registry, 9 (0.8%) met the criteria for leflunomide- or teriflunomide-related DILI; of 1400 DILIN patients, 8 (0.5%) met those criteria. Women accounted for 89% of the Indian cases. All Indian cases involved a severe cutaneous adverse reaction (SCAR), and the median time from drug exposure to liver injury was 49 days. In DILIN, 37.5% of cases were female, none exhibited SCAR, and the median time to injury was 166 days.
Hepatocellular injury, a pattern involving injury to liver cells, accounted for 70% of cases. It was more common in women than men (92% versus 20%) and was associated with a younger mean age (41 versus 59 years), a higher peak international normalized ratio (INR, a blood-clotting measure; 2.3 versus 1.2), and higher mortality (58% versus 0%).
Six patients from India died, including 2 of the 3 patients with myocarditis. One patient from the USA received a liver transplant.
The authors concluded that leflunomide-induced liver injury is predominantly hepatocellular. Compared with US DILIN patients, the Indian cohort had a predominance of women, and leflunomide hepatotoxicity was more likely to be accompanied by SCAR, a shorter time to injury and higher mortality. The differences between Indian and US subjects in skin involvement, immunoallergic features and outcomes suggest that genetic or environmental factors are important in the development of liver injury.
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