Liquid Liver Biopsy for Disease Diagnosis and Prognosis

Liver diseases are a major burden worldwide, the scope of which is expected to further grow in the upcoming years. Clinically relevant liver dysfunction-related blood markers such as alanine aminotransferase and aspartate aminotrans-ferase have limited accuracy. Nowadays, liver biopsy remains the gold standard for several liver-related pathologies, pos-ing a risk of complication due to its invasive nature. Liquid biopsy is a minimally invasive approach, which has shown substantial potential in the diagnosis, prognosis, and moni-toring of liver diseases by detecting disease-associated par-ticles such as proteins and RNA molecules in biological fluids. Histones are the core components of the nucleosomes, regu-lating essential cellular processes, including gene expression and DNA repair. Following cell death or activation of immune cells, histones are released in the extracellular space and can be detected in circulation. Histones are stable in circula-tion, have a long half-life, and retain their post-translational modifications. Here, we provide an overview of the current research on histone-mediated liquid biopsy methods for liver diseases, with a focus on the most common detection meth-ods.