Systematic Review: Ibuprofen-induced Liver Injury

Miguel E. Zoubek; María Isabel Lucena; Raúl J. Andrade; Camilla Stephens


Aliment Pharmacol Ther. 2020;51(6):603-611. 

In This Article


A systematic literature review was conducted in accordance with the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) guidelines, in order to identify all preexisting studies on ibuprofen-induced liver injury to date.

Systematic Database Search

Systematic electronic searches of PubMed, Cochrane and Web of Science were performed to obtain case reports and case series of ibuprofen-induced liver injury published up to December 2018. The searches were conducted using the terms "hepatotoxicity", "drug-induced liver injury" and "ibuprofen". An elevated number of ibuprofen-induced hepatotoxicity events related to the term "vanishing bile duct syndrome" was also observed. Thus, this term was included in a new search. Only articles published in English were considered. No other restrictions were applied.

Eligibility Criteria

After removing duplicates, titles and abstracts were screened independently for eligibility by two reviewers (MEZ and CS). Any disagreements were resolved by discussion between the two reviewers. Full articles corresponding to the selected abstracts and/or titles were obtained and assessed against eligibility criteria. Only cases where ibuprofen was judged as the single culprit drug causing a liver reaction were considered for our analysis. References cited by the selected articles were also reviewed to identify other potentially eligible studies not captured in the initial electronic database search.

Data Collection

Demographic, clinical, histological, laboratory and outcome information corresponding to exposure to ibuprofen resulting in hepatotoxicity was retrieved from the articles and analysed. The pattern of liver injury was classified based on R value calculations from the first available blood test after DILI recognition.[38] For those cases without complete analytical information at DILI recognition, histological findings from liver biopsies were carefully reviewed. Presentations considered as hypersensitivity features included fever, rash, eosinophilia and lymphopenia.