DILIN registry: HLA-B*35:01 found in 50% of 44 antihypertensive liver injury cases vs 13% in controls
Among 2207 DILIN cases, 44 were tied to antihypertensives. Carriers of the allele developed liver injury after a median of 50 days versus 109 days in non-carriers.
Researchers working with the US Drug-Induced Liver Injury Network (DILIN) analysed 2207 patients enrolled between 2003 and 2024 whose liver injury was adjudicated as definite, highly likely or probable. According to a paper in Acta Pharmaceutica Sinica B, 44 of these cases were attributed to antihypertensive drugs, about 2% of the registry 
doi.orgActa Pharmaceutica Sinica Bdoi.orgOpen source ↗. The cases were compared with non-antihypertensive DILI cases and with population controls doi.orgActa Pharmaceutica Sinica Bdoi.orgOpen source ↗. HLA sequencing was performed, and allele frequencies were analysed with Fisher's exact test doi.orgActa Pharmaceutica Sinica Bdoi.orgOpen source ↗.
Drug classes and clinical course
Of the 44 cases, 14 were caused by ACE inhibitors or angiotensin receptor blockers, 13 by methyldopa, 11 by hydralazine, and three each by beta-blockers and calcium-channel blockers doi.orgActa Pharmaceutica Sinica Bdoi.orgOpen source ↗. Methyldopa-related injury was hepatocellular and occurred in young women, to whom the drug was prescribed mainly for pregnancy-related hypertension doi.orgActa Pharmaceutica Sinica Bdoi.orgOpen source ↗.
Among the cases not related to methyldopa, 60% were hepatocellular, 28% cholestatic and 9% mixed doi.orgActa Pharmaceutica Sinica Bdoi.orgOpen source ↗. Severe outcomes included two liver transplants and two deaths, associated with lisinopril and hydralazine doi.orgActa Pharmaceutica Sinica Bdoi.orgOpen source ↗.
Association with HLA-B*35:01
The allele HLA-B*35:01 was found in 50% of antihypertensive cases against 13% in controls (odds ratio 6.0; P = 1×10⁻⁸) doi.orgActa Pharmaceutica Sinica Bdoi.orgOpen source ↗. It was overrepresented across all drug classes: in 66% of methyldopa cases, 27% of hydralazine cases and 42% of ACE inhibitor/ARB cases doi.orgActa Pharmaceutica Sinica Bdoi.orgOpen source ↗.
Carriers developed injury sooner after the start of treatment: latency was 50 days versus 109 days in non-carriers (P = 0.02) doi.orgActa Pharmaceutica Sinica Bdoi.orgOpen source ↗. Carriage was not linked to the severity of injury doi.orgActa Pharmaceutica Sinica Bdoi.orgOpen source ↗.
The authors note that the shorter latency may indicate an accelerated adaptive immune response and say this warrants further exploration doi.orgActa Pharmaceutica Sinica Bdoi.orgOpen source ↗. They also point out that the small number of cases limits the conclusions, and that further work is needed to establish the clinical value of the marker and the underlying mechanisms.
