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Plasma Sphingoid Base Profiles of Patients Diagnosed with Intrinsic or Idiosyncratic Drug-induced Liver Injury

Gai, Zhibo; Samodelov, Sophia L.; Alecu, Irina; Hornemann, Thorsten; Grove, Jane I.; Aithal, Guruprasad P.; Visentin, Michele; Kullak-Ublick, Gerd A


Zhibo Gai

Sophia L. Samodelov

Irina Alecu

Thorsten Hornemann

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Assistant Professor

Michele Visentin

Gerd A Kullak-Ublick


Sphingolipids are exceptionally diverse, comprising hundreds of unique species. The bulk of circulating sphingolipids are synthesized in the liver, thereby plasma sphingolipid profiles represent reliable surrogates of hepatic sphingolipid metabolism and content. As changes in plasma sphingolipid content have been associated to exposure to drugs inducing hepatotoxicity both in vitro and in rodents, in the present study the translatability of the preclinical data was assessed by analyzing the plasma of patients with suspected drug-induced liver injury (DILI) and control subjects. DILI patients, whether intrinsic or idiosyncratic cases, had no alterations in total sphingoid base levels and profile composition compared to controls, whereby cardiovascular disease (CVD) was a confounding factor. Upon exclusion of CVD individuals, elevation of 1-deoxysphingosine (1-deoxySO) in the DILI group emerged. Notably, 1-deoxySO values did not correlate with ALT values. While 1-deoxySO was elevated in all DILI cases, only intrinsic DILI cases concomitantly displayed reduction of select shorter chain sphingoid bases. Significant perturbation of the sphingolipid metabolism observed in this small exploratory clinical study is discussed and put into context, in the consideration that sphingolipids might contribute to the onset and progression of DILI, and that circulating sphingoid bases may function as mechanistic markers to study DILI pathophysiology.


Gai, Z., Samodelov, S. L., Alecu, I., Hornemann, T., Grove, J. I., Aithal, G. P., …Kullak-Ublick, G. A. (2023). Plasma Sphingoid Base Profiles of Patients Diagnosed with Intrinsic or Idiosyncratic Drug-induced Liver Injury. International Journal of Molecular Sciences, 24(3), Article 3013.

Journal Article Type Article
Acceptance Date Jan 30, 2023
Online Publication Date Feb 3, 2023
Publication Date Feb 1, 2023
Deposit Date Feb 3, 2023
Publicly Available Date Feb 15, 2023
Journal International Journal of Molecular Sciences
Print ISSN 1661-6596
Electronic ISSN 1422-0067
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 24
Issue 3
Article Number 3013
Keywords acetaminophen; deoxysphingolipids; drug-induced liver injury; DILI; paracetamol; sphingolipids
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