Liquid biopsy shows promise for monitoring, detecting liver disease

Last Updated: 2018-09-24

By Anne Harding

NEW YORK (Reuters Health) - Diseased liver cells can be detected in the peripheral blood, and those from patients with hepatocellular carcinoma (HCC) have a different gene expression profile than those from patients with chronic liver disease (CLD) but no cancer, according to new findings in Gastroenterology.

The authors also found that patients with CLD and more severe fibrosis had significantly more hepatic circulating epithelial cells (CECs) in their blood. "We're identifying cells that haven't been identified before," Dr. Irun Bhan of Massachusetts General Hospital (MGH) Cancer Center in Boston, the study's first author, told Reuters Health by phone. "Perhaps in the future they could even be used as biomarkers for these diseases."

Analysis of CECs collected in so-called liquid biopsies offers the possibility of non-invasive cancer detection, Dr. Bhan, Dr. David T. Ting of the MGH Cancer Center and their colleagues note in their September 14 report in Gastroenterology.

The authors previously reported on a cell-sorting device they developed, the iChip, which they combined with an RNA signature to enrich and detect HCC CECs in blood. MGH Cancer Center and Johnson & Johnson founded Torpedo Diagnostics to commercialize the technology platform.

In the new study, Dr. Bhan and colleagues tested the device for detecting hepatic CECs in 10 healthy volunteers, 39 with chronic liver disease (CLD) but no HCC, 54 with HCC, and 10 HCC patients who had undergone curative treatment and had no evidence of disease, using immunofluorescence to identify cells expressing glyptican-3 and the epithelial marker cytokeratin.

With a threshold of 5 cells per 10 mL of whole blood, the authors found hepatic CECs in 79% of CLD patients, 81% of HCC patients, 90% of the cured HCC patients, and 5% of healthy donors.

Patients with CLD and advanced fibrosis had a median of 5.1 cells/mL, compared to 0.7 cells/mL for those with CLD but without advanced fibrosis.

The authors also developed a classifier using gene expression profiling to distinguish between CLD and HCC. Testing in 64 CLD patients and 52 HCC patients showed preliminary sensitivity of 85% at 95% specificity.

"Biologically there's a lot that's left to be understood about these cells," Dr. Bhan said. "There's a lot of research opportunities to further phenotypically describe these cells in the context of different liver diseases."

For example, he noted, fatty liver has become a major health problem in the US, and a non-invasive test is needed to identify and stratify at-risk patients and monitor the effectiveness of potential treatments. "Our hope is that in the future this could be one of those tests."

SOURCE: http://bit.ly/2xB92v3

Gastroenterology 2018.

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