Atorvastatin-associated liver injury: a structured narrative review of reporting signals, clinical phenotypes, and hepatic safety, 2023–2026
Abstract
BackgroundAtorvastatin is widely prescribed, yet its hepatic safety remains debated: randomized trials and biopsy-proven cohorts indicate acceptable safety, whereas pharmacovigilance data and case reports describe injury ranging from asymptomatic transaminase elevation to acute liver failure.MethodsPubMed was searched for records combining atorvastatin terms with liver-injury concepts, published 1 July 2023 to 31 July 2026; records were screened in duplicate and assigned to one of four outcome domains—biochemical liver test abnormality, suspected drug-induced liver injury (DILI), clinically significant or severe DILI, and acute liver failure—and were not combined across domains. This is a structured narrative review, not a systematic review: only PubMed was searched and comprehensive retrieval is not claimed.ResultsOf 119 records, 57 were included in the synthesis: 31 directly addressed atorvastatin and liver injury and 26 addressed statin hepatic safety or statin use in chronic liver disease. Among 7,779 statin-associated drug-induced liver injury (DILI) cases in FAERS (2004–2023), atorvastatin accounted for 53.48%, with a reporting odds ratio of 3.09. In 1 211 reported Chinese cases of statin-associated liver injury, the odds of severe injury were 1.77-fold higher with atorvastatin than with rosuvastatin, and 2.08-fold higher with combination therapy than with statin monotherapy. Phenotypes included hepatocellular, cholestatic and mixed injury, drug-induced autoimmune hepatitis (DIAIH) and hyperacute liver failure, usually within 2–3 months. Rechallenge reproduced injury in 12 of 16 cases, with median latency shortened from 27 to 11 days, whereas switching to a hydrophilic statin was usually tolerated. Mechanisms involve mitochondrial dysfunction, oxidative stress, CYP3A-mediated metabolic activation, bile-acid transporter inhibition and pharmacogenomic variation. Conversely, in MASLD and cirrhosis, atorvastatin did not worsen liver injury and reduced liver-related events.ConclusionSevere atorvastatin-associated liver injury is rare but recognizable. Structured monitoring, causality assessment and injury phenotyping are essential, same-drug rechallenge should be avoided, and hydrophilic statins preferred. Statin therapy should not be withheld in chronic liver disease.
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BibTeX
@article{zhang2026atorvastatinassociated,
title = {{Atorvastatin-associated liver injury: a structured narrative review of reporting signals, clinical phenotypes, and hepatic safety, 2023–2026}},
author = {Hao Zhang and PanLi Zhao and Hua Huang and YuQi Zeng},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.2003438},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.2003438},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Atorvastatin-associated liver injury: a structured narrative review of reporting signals, clinical phenotypes, and hepatic safety, 2023–2026
AU - Hao Zhang
AU - PanLi Zhao
AU - Hua Huang
AU - YuQi Zeng
PY - 2026
DA - 2026/10/30
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.2003438
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.2003438
AB - BackgroundAtorvastatin is widely prescribed, yet its hepatic safety remains debated: randomized trials and biopsy-proven cohorts indicate acceptable safety, whereas pharmacovigilance data and case reports describe injury ranging from asymptomatic transaminase elevation to acute liver failure.MethodsPubMed was searched for records combining atorvastatin terms with liver-injury concepts, published 1 July 2023 to 31 July 2026; records were screened in duplicate and assigned to one of four outcome domains—biochemical liver test abnormality, suspected drug-induced liver injury (DILI), clinically significant or severe DILI, and acute liver failure—and were not combined across domains. This is a structured narrative review, not a systematic review: only PubMed was searched and comprehensive retrieval is not claimed.ResultsOf 119 records, 57 were included in the synthesis: 31 directly addressed atorvastatin and liver injury and 26 addressed statin hepatic safety or statin use in chronic liver disease. Among 7,779 statin-associated drug-induced liver injury (DILI) cases in FAERS (2004–2023), atorvastatin accounted for 53.48%, with a reporting odds ratio of 3.09. In 1 211 reported Chinese cases of statin-associated liver injury, the odds of severe injury were 1.77-fold higher with atorvastatin than with rosuvastatin, and 2.08-fold higher with combination therapy than with statin monotherapy. Phenotypes included hepatocellular, cholestatic and mixed injury, drug-induced autoimmune hepatitis (DIAIH) and hyperacute liver failure, usually within 2–3 months. Rechallenge reproduced injury in 12 of 16 cases, with median latency shortened from 27 to 11 days, whereas switching to a hydrophilic statin was usually tolerated. Mechanisms involve mitochondrial dysfunction, oxidative stress, CYP3A-mediated metabolic activation, bile-acid transporter inhibition and pharmacogenomic variation. Conversely, in MASLD and cirrhosis, atorvastatin did not worsen liver injury and reduced liver-related events.ConclusionSevere atorvastatin-associated liver injury is rare but recognizable. Structured monitoring, causality assessment and injury phenotyping are essential, same-drug rechallenge should be avoided, and hydrophilic statins preferred. Statin therapy should not be withheld in chronic liver disease.
SN - 1663-9812
ER -