Atorvastatin-Associated Liver Injury: Outcome After Statin Rechallenge

IF 2.5 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology Pub Date : 2026-02-15 DOI:10.1111/fcp.70073

Blandine Bertin, Valentine Lacotte, Jean-Luc Cracowski, Anais Gaiffe, Jérôme Dumortier, Thierry Vial

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Abstract

Background

Statin-induced liver injury is frequent and usually not severe. The aim of the present study was to describe the safety of statin rechallenge after atorvastatin-induced liver injury because it is poorly documented.

Methods

Cases of liver injury involving atorvastatin were selected from the French pharmacovigilance database. Inclusion criteria were a documented atorvastatin or any other statin reintroduction and an available follow-up of at least 2 weeks to define negative rechallenge.

Results

Twenty-six cases of atorvastatin liver injury with further statin reintroduction met our criteria. Median time to onset (TTO) of the first episode was 27 days (IQR: 4–43), with a cholestatic pattern in 11 (42.3%) cases, cytolytic in nine (34.6%), and mixed in six (23.1%); severity ranked Grade 2 in 11 (42.3%). Atorvastatin rechallenge was positive in 12 of 16 patients with the same dose (11 of 13) or a reduced dose (1 of 3), and the TTO was shorter (median 11 days). Rechallenge with an alternative statin was performed in 10 patients, of whom two experienced recurrence with rosuvastatin and simvastatin. No recurrence was observed after rechallenge of rosuvastatin in five, pravastatin in two, and simvastatin in one.

Conclusion

Our study evidenced frequent recurrence of drug-induced liver injury after atorvastatin rechallenge, whereas subsequent administration of a hydrophilic statin was well tolerated. By combining our data and published cases, we suggest that rosuvastatin or pravastatin carries the lowest risk of recurrence. Study limitations include a focus solely on atorvastatin, a retrospective design, and potential underreporting to the pharmacovigilance system.

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阿托伐他汀相关肝损伤：他汀再挑战后的结果

背景：他汀类药物引起的肝损伤是常见的，通常不严重。本研究的目的是描述阿托伐他汀诱导的肝损伤后他汀再灌注的安全性，因为这方面的文献很少。方法：从法国药物警戒数据库中选择涉及阿托伐他汀的肝损伤病例。纳入标准是有记录的阿托伐他汀或任何其他他汀类药物重新引入，以及至少2周的随访以确定阴性再挑战。结果：26例阿托伐他汀肝损伤患者符合我们的标准。首次发作的中位发病时间（TTO）为27天（IQR: 4-43），其中11例（42.3%）为胆汁淤积型，9例（34.6%）为细胞溶解型，6例（23.1%）为混合型；严重程度在11人中排名第2级（42.3%）。相同剂量（11 / 13）或减少剂量（1 / 3）的16例患者中有12例阿托伐他汀再挑战呈阳性，并且TTO较短（中位11天）。10例患者再次接受他汀类药物替代治疗，其中2例接受瑞舒伐他汀和辛伐他汀治疗复发。再次服用瑞舒伐他汀5例，普伐他汀2例，辛伐他汀1例，未见复发。结论：我们的研究证明，阿托伐他汀再灌注后药物性肝损伤经常复发，而随后给予亲水他汀类药物耐受性良好。通过结合我们的数据和已发表的病例，我们认为瑞舒伐他汀或普伐他汀具有最低的复发风险。研究的局限性包括仅关注阿托伐他汀，回顾性设计，以及对药物警戒系统的潜在漏报。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Fundamental & Clinical Pharmacology 医学-药学

CiteScore

5.30

自引率

6.90%

发文量

111

审稿时长

6-12 weeks

期刊介绍： Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.