Abstract

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the fourth leading cause of cancer-related death. The most common risk factor for developing HCC is chronic infection with hepatitis B virus (HBV). Early stages of HBV-related HCC (HBV-HCC) are generally asymptomatic. Moreover, while serum alpha-fetoprotein (AFP) and abdominal ultrasound are widely used to screen for HCC, they have poor sensitivity. Thus, HBV-HCC is frequently diagnosed at an advanced stage, in which there are limited treatment options and high mortality rates. Serum biomarkers with high sensitivity and specificity are crucial for earlier diagnosis of HCC and improving survival rates. As viral–host interactions are key determinants of pathogenesis, viral biomarkers may add greater diagnostic power for HCC than host biomarkers alone. In this review, we summarize recent research on using virus-derived biomarkers for predicting HCC occurrence and recurrence; including circulating viral DNA, RNA transcripts, and viral proteins. Combining these viral biomarkers with AFP and abdominal ultrasound could improve sensitivity and specificity of early diagnosis, increasing the survival of patients with HBV-HCC. In the future, as the mechanisms that drive HBV-HCC to become clearer, new biomarkers may be identified which can further improve early diagnosis of HBV-HCC.

Highlights

  • Chronic infection with the Hepatitis B virus (HBV) is the predominant risk factor for primary liver cancer, hepatocellular carcinoma (HCC; Bosch et al, 2004; Kew, 2010; Ozakyol, 2017)

  • nucleo(s/t)ide analogs (NAs) suppress viral replication (Ghany and Liang, 2007) but do not target HBV covalently closed circular DNA. cccDNA is the template for HBV replication and expression of viral proteins, so its persistence plays a crucial role in chronic infection, inflammation, and cancer formation

  • HBV DNA was not different between HCC and non-HCC HBV DNA is higher in HCC group (AUROC = 0.62) AUROC = 0.7 HBV DNA was not different between HCC and non-HCC Risk of HCC is significantly higher in low-level viremia (

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Summary

Introduction

Chronic infection with the Hepatitis B virus (HBV) is the predominant risk factor for primary liver cancer, hepatocellular carcinoma (HCC; Bosch et al, 2004; Kew, 2010; Ozakyol, 2017). Performance as a Predictor of HCC HCC occurrence In NA-naïve patients, two studies in Taiwan have inferred that elevated serum HBV DNA level can be a useful biomarker for monitoring HCC independent of HBeAg and liver cirrhosis (Chen et al, 2006, 2011).

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