Genetic variant tied to liver injury from blood pressure drugs

This new article publication from Acta Pharmaceutica Sinica B discusses the clinical features and genetic associations of rare liver injury caused by antihypertensive medications.

Antihypertensive medications are widely prescribed, but the clinical features and genetic susceptibility underlying the liver injury they occasionally cause remain poorly understood. The authors of this article examined 2,207 high-confidence cases of drug-induced liver injury (DILI) enrolled in the U.S. Drug-Induced Liver Injury Network between 2003 and 2024. Of these, 44 cases were attributed to antihypertensive drugs, representing 2% of the registry's DILI cases.

These included 14 cases associated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, 13 with methyldopa, 11 with hydralazine, and three each with beta-blockers and calcium-channel blockers. Clinical presentations varied by drug. Methyldopa-related injury occurred in young women and consistently involved liver-cell damage, while other agents produced a range of injury patterns. Although uncommon, severe injury occurred, with two patients requiring liver transplantation.

Genetic analysis identified the human leukocyte antigen variant HLA-B*35:01 in half of the antihypertensive-related cases, compared with 11% of patients whose liver injury was attributed to other agents (odds ratio 6.0; 95% confidence interval 3.4-10.6; P = 1 × 10⁻⁸). The association was particularly strong for methyldopa. Carriers developed liver injury sooner after starting treatment than non-carriers, with reported onset times of 50 versus 109 days, but carriage was not associated with injury severity. The findings suggest a possible role for an accelerated adaptive immune response and identify HLA-B*35:01 as a potential marker of susceptibility. The small number of cases limits the conclusions, and further research is needed to establish the marker's clinical value and clarify the underlying mechanisms.