MicroRNA Biomarkers in Drug-Induced Liver Injury

Drug-induced liver injury (DILI) represents a major challenge in clinical practice and drug development, owing to its unpredictable onset and potential severity. MicroRNAs (miRNAs) have emerged as sensitive and tissue-specific biomarkers that circulate stably in blood and reflect hepatocellular damage. These small non-coding RNAs regulate gene expression in hepatocytes and are released into the bloodstream upon injury, often packaged within exosomes. Profiling circulating miRNAs offers a minimally invasive approach to detect early liver injury, distinguish DILI from other hepatic or renal insults and monitor recovery. Their high specificity, dynamic range and capacity to reveal underlying pathogenic mechanisms position miRNA biomarkers as promising tools for personalised risk assessment, real-time monitoring of drug safety and guiding therapeutic interventions.

Research from Nature Portfolio

A foundational study employed comprehensive plasma miRNA profiling in patients with acetaminophen overdose to identify a 16-miRNA classifier that discriminates acute liver injury from non-toxic controls. Key miRNAs such as miR-122-5p, miR-885-5p and miR-382-5p demonstrated greater sensitivity than alanine aminotransferase at hospital presentation and remained unaffected by concomitant kidney injury. This work established circulating miRNAs as robust, early indicators of hepatotoxicity and set a benchmark for subsequent biomarker development.

MicroRNA Biomarkers in Drug-Induced Liver Injury publication trend

The graph below shows the total number of articles in microrna biomarkers in drug-induced liver injury across all publications each year (not limited to Nature Index journals).

Technical terms

microRNA (miRNA): Small non-coding RNA molecules (~18–25 nucleotides) that regulate gene expression post-transcriptionally.

Drug-induced liver injury (DILI): Hepatic damage caused by pharmaceuticals or herbal compounds, ranging from mild enzyme elevation to acute liver failure.

Exosome: Extracellular vesicle (30–150 nm) released by cells, carrying proteins, lipids and nucleic acids, including miRNAs.

Hepatocyte: Principal liver cell type responsible for metabolism, detoxification and protein synthesis.

Alanine aminotransferase (ALT): Enzyme released into blood upon hepatocyte injury, routinely used as a clinical marker of liver damage.

References

1. miR‐106b‐5p protects against drug‐induced liver injury by targeting vimentin to stimulate liver regeneration. MedComm (2024).
2. Comprehensive microRNA profiling in acetaminophen toxicity identifies novel circulating biomarkers for human liver and kidney injury. Scientific Reports (2015).
3. A Panel of Serum MicroRNAs as Specific Biomarkers for Diagnosis of Compound- and Herb-Induced Liver Injury in Rats. PLOS ONE (2012).
4. Serum microRNA signatures as "liquid biopsies" for interrogating hepatotoxic mechanisms and liver pathogenesis in human. PLOS ONE (2017).