{"id":2923,"date":"2026-08-22T15:50:43","date_gmt":"2026-08-22T14:50:43","guid":{"rendered":"https:\/\/seamlessbio.de\/?page_id=2923"},"modified":"2026-08-23T00:52:37","modified_gmt":"2026-08-22T23:52:37","slug":"what-is-dili-drug-induced-liver-injury","status":"publish","type":"page","link":"https:\/\/seamlessbio.de\/de\/what-is-dili-drug-induced-liver-injury\/","title":{"rendered":"What is DILI (Drug-Induced Liver Injury)?"},"content":{"rendered":"
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Quick Definition<\/p>\n

What is DILI (Drug-Induced Liver Injury)?:<\/strong> Drug-induced liver injury (DILI) is hepatotoxicity caused by a pharmaceutical drug or herbal supplement. It is the most common cause of acute liver failure in Western countries and the leading cause of drug withdrawal from the market post-approval. DILI ranges from asymptomatic liver enzyme elevation to fulminant hepatic failure.<\/p>\n<\/div>\n\n

How does BSEP inhibition cause DILI?<\/h2>\n

BSEP (ABCB11) is the primary transporter responsible for secreting bile salts from hepatocytes into bile. Drugs that inhibit BSEP cause bile salt accumulation inside hepatocytes. At toxic concentrations, bile salts disrupt mitochondrial membrane potential, generate reactive oxygen species, activate the intrinsic apoptosis pathway, and cause direct membrane lysis. The clinical result is cholestatic hepatitis \u2014 a pattern characterised by disproportionate alkaline phosphatase and GGT elevation relative to transaminases.<\/p>\n\n

Examples of BSEP inhibition-mediated DILI<\/h2>\n

Troglitazone (withdrawn 2000), bosentan (black box warning), cyclosporin A (clinical monitoring required), and rifampicin all cause cholestatic DILI through BSEP inhibition. In vitro BSEP IC50 values for these drugs correlate with their clinical hepatotoxicity risk \u2014 validating the vesicular transport assay as a predictive preclinical tool.<\/p>\n\n

How is DILI risk assessed preclinically?<\/h2>\n

BSEP inhibition is assessed using the inside-out membrane vesicle assay with taurocholic acid as probe substrate. The IC50 is compared to estimated unbound hepatic drug concentration. Additional DILI risk signals come from: MRP2 inhibition, mitochondrial membrane potential disruption (JC-1 assay), reactive metabolite formation (GSH trapping), and covalent protein binding.<\/p>\n\n

Key Facts<\/h2>\n