From the Journals

Despite HCV cure, liver cancer-associated genetic changes persist



A new study showed that liver tissue from hepatitis C virus (HCV)–infected humans with and without sustained virologic response found epigenetic and gene expression alterations associated with the risk for hepatocellular carcinoma (HCC), according to Nourdine Hamdane, PHD, of the Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France, and colleagues.

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The researchers analyzed liver tissue from 6 noninfected control patients, 18 patients with chronic HCV infection, 21 patients with cured chronic HCV, 4 patients with hepatitis B virus (HBV) infection, and 7 patients with nonalcoholic steatohepatitis (NASH), as well as 8 paired HCC samples with HCV-induced liver disease (Gastroenterology 2019;156:2313–29).

They found that several altered pathways related to carcinogenesis persisted after cure, including TNF-alpha signaling, inflammatory response, G2M checkpoint, epithelial–mesenchymal transition, and phosphoinositide 3-kinase, Akt, and mammalian target of rapamycin.

They also observed lower levels of H3K27ac mapping to genes related to oxidative phosphorylation pathways, providing evidence supporting a functional role for H3K27ac changes in establishing gene expression patterns that persist after cure and contribute to carcinogenesis, according to the authors.

“Our study exposes a previously undiscovered paradigm showing that chronic HCV infection induces H3K27ac modifications that are associated with HCC risk and that persist after HCV cure,” the authors wrote. “[This study] provides a unique opportunity to uncover novel biomarkers for HCC risk, that is, from plasma through the detection of epigenetic changes of histones bound to circulating DNA complexes. Furthermore, by uncovering virus-induced epigenetic changes as therapeutic targets, our findings offer novel perspectives for HCC prevention – a key unmet medical need,” the researchers concluded.

The authors declared that they had no conflicts.

SOURCE: Hamdane N, et al. 2019; Gastroenterology 156:2313–29.

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