Cell-free DNA methylation as liquid biopsy for the assessment of fibrosis in patients with nonalcoholic steatohepatitis: a gap between innovation and implementation

Abstract

The presence of cfDNA in the circulating compartment was demonstrated three decades ago , leading to the emergence of liquid biopsy.However, the implementation of cfDNA methylation as a non-invasive molecular tool for the diagnosis of fibrosis imposes tremendous analytical and technical challenges because cfDNA is not only highly fragmented (~170?500 bp) but also circulates at very low concentrations (1.8?44 ng/mL). The fact that exploration of DNA methylation signatures requires a previous step of DNA bisulfitation or other complex and protracted techniques, such as 5mC-containing DNA immunoprecipitation and sequencing, imposes further obstacles to the adoption of this method. Available evidence suggests that a considerable gap between innovation and implementation still exists, preventing definitive affirmation that plasma DNA methylation signatures reflect the molecular pathology associated with fibrotic liver disease. Nonetheless, this is a promising horizon toward which further research efforts should be directed.