https://doi.org/10.1016/j.apsb.2026.06.003
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.
Keywords: Hepatotoxicity, DILI, Genetics, Hypertension, Methyldopa, Hydralazine, Lisinopril, Single nucleotide polymorphism
Graphical Abstract: available at
https://ars.els-cdn.com/content/image/1-s2.0-S2211383526003345-ga1_lrg.jpg
HLA-B∗35:01 is associated with susceptibility to anti-hypertensive DILI, particularly hepatocellular injury, and is linked to an accelerated immune response with shorter latency.
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The Journal of the
Institute of Materia Medica, the Chinese Academy of Medical Sciences and the
Chinese Pharmaceutical Association.
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CiteScore: 24.4
Impact Factor: 14.6 (Top 8 journal in the category of Pharmacology and pharmacy)
JIF without self-citation: 14.0
ISSN 2211-3835
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Lily Dara, Paola Nicoletti, Chaudry Nasir Majeed, Andrew Dellinger, David E. Kleiner, Mahmoud G. Mohamed, Tatyana Kushner, Raj Vuppalanchi, Elizabeth J Phillips, David A. Ostrov, Mohammed Umair Masood, Huiman Barnhart, Jiezhun Gu, Herbert L. Bonkovsky, Antihypertensive drug-induced liver injury is rare, but strongly associated with HLA-B*35:01, Acta Pharmaceutica Sinica B, Volume 16, Issue 10, 2026, Pages 6676–6685, ISSN 2211-3835,
https://doi.org/10.1016/j.apsb.2026.06.003