The intracellular HBV DNAs as novel and sensitive biomarkers for the clinical diagnosis of occult HBV infection in HBeAg negative hepatocellular carcinoma in China.

Hui Wang,Shu-Qun Cheng,Chun-Fang Gao,Meng Fang,Qiang Ji,Dongdi Li,Xing Gu,Feng Shen

doi:10.1371/journal.pone.0107162

Abstract

This study aimed to investigate the virological status in liver (both tumor and adjacent non-tumor tissue), the clinical features and the contribution of occult HBV infection (OBI) to postoperative prognosis in HBeAg-negative(−) hepatocellular carcinoma (HCC) patients in China. Using quantitative TaqMan fluorescent real-time PCR assays, HBV covalently closed circular DNA (cccDNA) and total DNA (tDNA) were both quantified in 11 (HBsAg(−)) and 57 (HBsAg-positive(+)) pairs of tumor tissue (TT) and adjacent non-tumor tissue (ANTT) obtained from HBeAg(−) HCC patients who received no antiviral treatment and were negative for anti-HCV before surgical treatment. Of 11 HBsAg(−) patients, 36% were with HBsAb(+) HBeAb(+) HBcAb(+). However, only 9% of the HBsAg(−) patients were HBsAb(−) HBeAb(+) HBcAb(+), which accounted for the majority (93%) in the HBsAg(+) group. TT and ANTT HBV tDNAs in 11 HCC patients with HBsAg (−) and HBeAg (−) were all detectable. HBV cccDNA and tDNA were all lower in the HBsAg(−) group than those in the HBsAg(+) group. By Kaplan-Meier analysis, patients with OBI were associated with a lower risk of cirrhosis and better overall survival (OS). The intracellular HBV DNAs, such as HBV cccDNA and tDNA are valuable biological markers for the diagnosis of occult HBV infection in HCC patients. This would assist the clinical implementation of a more personalized therapy for viral re-activation control and improve the survival rate of OBI patients.

Highlights

Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide [1,2]
Several previous studies have reported the existence of hepatitis B virus (HBV) DNA in liver tissues of HBs antigen (HBsAg)-negative patients [10,11,12,13] and the occult HBV infection (OBI) significantly correlated with cirrhosis in chronic hepatitis C virus (HCV) carriers [14,15,16]
The long-lasting persistence of HBV genomes in the liver is termed OBI [17]

Summary

Introduction

Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide [1,2]. OBI can occur in individuals with anti-HBs and/or anti-HBc antibodies and in those who are negative for HBV markers [5,6]. The seronegativity in these OBI patients may be caused by naturally occurring mutants of HBV, which alters either the immunoreactivity of various HBV proteins or the quantity of serum HBsAg [7]. OBI is a worldwide diffused entity, evidence showed that this condition might be potentially oncogenetic [5,17] In those HCC patients with HBsAg and HBeAg negative, the virologic status and the clinical features of OBI are still not thoroughly studied

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Conclusion