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Updated: Mar 13, 2026
Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
Published on: January 31, 2022
Exploration of Biomarkers for Amoxicillin/Clavulanate-Induced Liver Injury: Multi-Omics Approaches
1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
Abstract:
To explore potential biomarkers for amoxicillin/clavulanate-induced liver injury (AC-DILI), we conducted a clinical trial in 32 healthy subjects based on multi-omics approaches. Every subject was administered amoxicillin/clavulanate for 14 days. The liver-specific microRNA-122 (miR-122) level increased prior to and correlated well with the observed alanine aminotransferase (ALT) level increase. This result indicates its potential as a sensitive early marker for AC-DILI. We also identified urinary metabolites, such as azelaic acid and 7-methylxanthine, with levels that significantly differed among the groups classified by ALT elevation level on day 8 after drug administration (P < 0.05). Lymphocyte proliferation in response to the drug was also observed. These findings demonstrate sequential changes in the process of AC-DILI, including metabolic changes, increased miR-122 level, increased liver enzyme activity, and enhanced lymphocyte proliferation after drug administration. In conclusion, this study provides potential biomarkers for AC-DILI based on currently known mechanisms using comprehensive multi-omics approaches.
Insights
Researchers identified potential early biomarkers for amoxicillin/clavulanate-induced liver injury (AC-DILI). MicroRNA-122 and specific urinary metabolites show promise for detecting AC-DILI, aiding in early diagnosis and management.
Area of Science:
- Hepatology
- Pharmacology
- Biomarker Discovery
Background:
- Amoxicillin/clavulanate is a common antibiotic associated with drug-induced liver injury (DILI).
- Early and accurate detection of DILI is crucial for patient management and preventing severe outcomes.
- Current diagnostic methods for DILI may lack sensitivity for early-stage detection.
Purpose of the Study:
- To identify novel biomarkers for amoxicillin/clavulanate-induced liver injury (AC-DILI).
- To investigate the utility of microRNA-122 and urinary metabolites as early indicators of AC-DILI.
- To explore the sequential biological changes associated with AC-DILI.
Main Methods:
- A clinical trial involving 32 healthy subjects administered amoxicillin/clavulanate for 14 days.
- Multi-omics approaches including analysis of microRNA and urinary metabolites.
- Monitoring of liver enzymes (ALT) and lymphocyte proliferation.
Main Results:
- Liver-specific microRNA-122 (miR-122) levels increased and correlated with alanine aminotransferase (ALT) elevations, suggesting it as a sensitive early marker.
- Urinary metabolites, including azelaic acid and 7-methylxanthine, showed significant differences based on ALT elevation.
- Observed sequential changes: metabolic alterations, increased miR-122, elevated liver enzymes, and enhanced lymphocyte proliferation.
Conclusions:
- MicroRNA-122 and specific urinary metabolites are potential sensitive biomarkers for early detection of AC-DILI.
- Multi-omics approaches provide comprehensive insights into the mechanisms of AC-DILI.
- These findings can aid in the development of improved diagnostic strategies for antibiotic-induced liver injury.
