Abstract
Despite breakthroughs in antiviral therapies, chronic viral hepatitis B and C are still the major causes of liver fibrosis and hepatocellular carcinoma (HCC). Importantly, even in patients with controlled infection or viral cure, the cancer risk cannot be fully eliminated, highlighting a persisting oncogenic pressure imposed by epigenetic imprinting and advanced liver disease. Reliable and minimally invasive biomarkers for early fibrosis and for residual HCC risk in HCV-cured patients are urgently needed. Chronic infection with HBV and/or HCV dysregulates oncogenic and profibrogenic signaling within the host, also displayed in the secretion of soluble factors to the blood. The study of virus-dysregulated signaling pathways may, therefore, contribute to the identification of reliable minimally invasive biomarkers for the detection of patients at early-stage liver disease potentially complementing existing noninvasive methods in clinics. With a focus on virus-induced signaling events, this review provides an overview of candidate blood biomarkers for liver disease and HCC risk associated with chronic viral hepatitis and epigenetic viral footprints.
Highlights
In Europe, it is estimated that 10–15% of hepatocellular carcinoma (HCC) are caused by hepatitis B virus (HBV) infection, while 70% are caused by hepatitis C virus (HCV) infection, HCV being the major risk factor for HCC development [10]
Both viruses contribute to liver fibrosis and HCC risk by multiple factors involving a dysregulation of host signal transduction through viral proteins, miRNAs, virus-induced growth factor and cytokine expression or antiviral responses that cumulate in a pro-fibrotic and pro-oncogenic environment in the liver [11,12,13,14,15,16,17]
With a focus on virus-induced signaling events, this review provides an overview of the candidate blood biomarkers of fibrotic liver disease and HCC risk associated with chronic viral hepatitis
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. An estimated 180 million people live with hepatitis B virus (HBV) and 75 million with hepatitis C virus (HCV), and for most, testing and treatment remain beyond reach [9] Both viruses share similar as well as distinct mechanisms contributing to liver disease and cancer. In Europe, it is estimated that 10–15% of HCCs are caused by HBV infection, while 70% are caused by HCV infection, HCV being the major risk factor for HCC development [10] Both viruses contribute to liver fibrosis and HCC risk by multiple factors involving a dysregulation of host signal transduction through viral proteins, miRNAs, virus-induced growth factor and cytokine expression or antiviral responses that cumulate in a pro-fibrotic and pro-oncogenic environment in the liver [11,12,13,14,15,16,17]. With a focus on virus-induced signaling events, this review provides an overview of the candidate blood biomarkers of fibrotic liver disease and HCC risk associated with chronic viral hepatitis
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