{
  "abstract": "Anti-hypertensive (anti-HTN) drugs are widely prescribed, but the features of associated drug-induced liver injury (DILI) are poorly defined. A total of 2207 patients enrolled in the Drug-Induced Liver Injury Network (DILIN) from 2003 to 2024 were adjudicated as definite, highly likely, or probable DILI. Of these, 44 cases were attributed to anti-HTN drugs. These were compared with non-anti-HTN DILI cases and population controls. Human Leukocyte Antigen (HLA) sequencing was performed, and allele frequencies were analyzed using Fisher's Exact Test. Among the 44 anti-HTN DILI cases, 14 were caused by ACE inhibitors/ARBs, 13 by methyldopa, 11 by hydralazine, and 3 each by beta-blockers and calcium-channel blockers. Methyldopa DILI presented with hepatocellular injury in young women (prescribed mainly for pregnancy-related HTN). Non-methyldopa cases were 60% hepatocellular, 28% cholestatic, and 9% mixed. Severe outcomes included two liver transplants and two deaths (lisinopril and hydralazine). HLA-B∗35:01 was markedly enriched (50% vs. 13% in controls; OR 6.0; P = 1 × 10⁻⁸) and was linked to shorter latency (50 vs. 109 days; P = 0.02) but not severity. HLA-B∗35:01 was overrepresented across all drug classes, including 66% of methyldopa cases, 27% of hydralazine cases, and 42% of ACE/ARB cases. DILI from anti-HTN medications is very rare but strongly associated with HLA-B∗35:01, especially for methyldopa. Carriers display a shorter latency, potentially indicating an accelerated adaptive immune response, that warrants further exploration.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Gastrointestinal and Liver Diseases, Research Center for Liver Diseases, Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA.",
    "Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.",
    "Section on Gastroenterology and Hepatology, Department of Medicine, Wake Forest University School of Medicine and Advocate Health Wake Forest Baptist, Winston-Salem, NC 27101, USA.",
    "Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC 27710, USA.",
    "Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892, USA.",
    "Department of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY 10065, USA.",
    "Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine and Indiana University Health, Indianapolis, IN 46202, USA.",
    "Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.",
    "Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610, USA.",
    "Duke Clinical Research Institute, Durham, NC 27710, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Lily Dara"
    },
    {
      "affs": [
        1
      ],
      "name": "Paola Nicoletti"
    },
    {
      "affs": [
        2
      ],
      "name": "Chaudry Nasir Majeed"
    },
    {
      "affs": [
        3
      ],
      "name": "Andrew Dellinger"
    },
    {
      "affs": [
        4
      ],
      "name": "David E Kleiner"
    },
    {
      "affs": [
        0
      ],
      "name": "Mahmoud G Mohamed"
    },
    {
      "affs": [
        5
      ],
      "name": "Tatyana Kushner"
    },
    {
      "affs": [
        6
      ],
      "name": "Raj Vuppalanchi"
    },
    {
      "affs": [
        7
      ],
      "name": "Elizabeth J Phillips"
    },
    {
      "affs": [
        8
      ],
      "name": "David A Ostrov"
    },
    {
      "affs": [
        1
      ],
      "name": "Mohammed Umair Masood"
    },
    {
      "affs": [
        9
      ],
      "name": "Huiman Barnhart"
    },
    {
      "affs": [
        9
      ],
      "name": "Jiezhun Gu"
    },
    {
      "affs": [
        2
      ],
      "name": "Herbert L Bonkovsky"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fy8afdze7mk1h.bib",
  "cited_by": 0,
  "doi": "10.1016/j.apsb.2026.06.003",
  "fulltext_url": "https://europepmc.org/articles/PMC13712353",
  "id": "fy8afdze7mk1h",
  "issns": [
    "2211-3835",
    "2211-3843"
  ],
  "landing_url": "https://europepmc.org/article/MED/42948728",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "3004|Drug-Induced Hepatotoxicity and Protection"
    ]
  ],
  "openalex": "W7164207001",
  "pdf_url": "https://europepmc.org/articles/PMC13712353?pdf=render",
  "pmcid": "PMC13712353",
  "pmid": "42948728",
  "published": "2026-06-10",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/fy8afdze7mk1h.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:36Z",
      "native_id": "MED:42948728",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42948728"
    },
    {
      "first_seen": "2026-10-31T12:22:57Z",
      "native_id": "PMC13712353",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.apsb.2026.06.003"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:3004|Drug-Induced Hepatotoxicity and Protection",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Antihypertensive drug-induced liver injury is rare, but strongly associated with HLA-B∗35:01.",
  "title_text": "Antihypertensive drug-induced liver injury is rare, but strongly associated with HLA-B∗35:01.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:22:57Z",
  "url": "https://research.draconitic.com/paper/fy8afdze7mk1h",
  "venue": "Acta pharmaceutica Sinica. B",
  "versions": []
}