Plasma cell-free DNA methylation: a liquid biomarker of hepatic fibrosis

We recently reported dynamic epigenetic markers of fibrosis detectable in patients' plasma that may have utility in non-invasive diagnosis and staging of fibrosis in patients with chronic liver disease.1 Specifically, we uncovered DNA methylation markers at the human PPAR promoter detectable in circulating cell-free DNA (ccfDNA) that display differential methylation densities. Remarkably, PPAR hypermethylation correlated with progression to cirrhosis in alcoholic liver disease (ALD) and with specific stages of liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Furthermore, ccfDNA signatures were traced back to the molecular pathology in fibrotic liver tissue, providing a biomarker of the underlying pathological process and defining hepatocytes as the source of hypermethylated DNA found in plasma.1

The original study posed several important outstanding questions: (1) Can ccfDNA methylation be used as a biomarker of fibrosis in liver diseases of other aetiologies? (2) Does the presence of hepatocellular carcinoma (HCC) alter the biomarker...

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