Exploration of the clinical characteristics and potential mechanisms of liver injury induced by proton pump inhibitors.

Background and aims: Data related to clinical characteristics and potential mechanisms of proton pump inhibitors (PPIs)-related liver injury are sparse, thus the purpose of this study is to summarize the clinical features and molecular mechanisms of PPIs-induced liver injury.

Methods: We collected case report on liver injury induced by PPIs in English and Chinese for retrospective analysis. Clinical and pathological data and outcomes were obtained and analyzed. Network pharmacology and molecular docking techniques were employed to examine the mechanism.

Result: Twenty-three patients with PPIs-induced liver injury were enrolled. PPIs-induced liver injury is a rare adverse reaction, ranging from asymptomatic elevated transaminases to fulminant liver failure. Omeprazole was the drug with the highest number of associated reports. The most common symptom was fatigue. The most common liver injury pattern was hepatocellular injury. A total of 13 intersection targets of PPIs and liver injury were screened, and the top 10 targets were included, and the PI3K-Akt signaling pathway was significantly enriched. The results of molecular docking implied that the PPIs could combine well with key targets.

Conclusion: Patients receiving long-term treatment with PPIs should consider monitoring liver function. PPIs exhibit considerable capacity in liver injury via especially the PI3K-Akt signaling pathway.