Hepatic Clearance of Cell-Free DNA: Possible Impact on Early Metastasis Diagnosis

Circulating DNA in the bloodstream has been studied since the 1940s, leading to its identification as a possible early marker for the presence of a primary tumor. Recently, it has been more successfully employed in liquid biopsies to determine the early presence of a metastatic tumor arising after chemotherapy, radiotherapy, and surgery. The appearance of such circulating tumor DNA permits the identification of the metastatic tumor before it is detected by either palpation or radiological analysis. Nevertheless, the liquid biopsy may possibly be affected by the removal of circulating tumor DNA via the kidneys and spleen as it is released. Furthermore, the liver removal of cell-free DNA has not yet been considered to be involved in this process. Here, we review the literature on the removal of free single- and double-stranded DNA and nucleosomal, vesicular, and exosomal DNA via the liver and examine its possible impact on circulating DNA levels. The removal of all forms of DNA by the liver, together with that removed by the kidneys and spleen, may delay the timing of positive results from liquid biopsies.