SAT-182-Full length deep sequencing of South African hepatitis B virus isolates reveals increased viral diversity and X-gene deletions in hepatocellular carcinoma patients

Hepatocellular carcinoma (HCC) is one of the most frequent and fatal human cancers worldwide and its development and prognosis are intimately associated with chronic infection with hepatitis B virus (HBV). The identification of genetic mutations and molecular mechanisms that mediate HBV-induced tumorigenesis therefore holds promise for the development of potential biomarkers and targets for HCC prevention and therapy. The presence of HBV pre-S gene deletions in the blood and the expression of pre-S deleted proteins in the liver tissues of patients with chronic hepatitis B and HBV-related HCC have emerged as valuable biomarkers for higher incidence rates of HCC development and a higher risk of HCC recurrence after curative surgical resection, respectively. Moreover, pre-S deleted proteins are regarded as important oncoproteins that activate multiple signaling pathways to induce DNA damage and promote growth and proliferation in hepatocytes, leading to HCC development. The signaling molecules dysregulated by pre-S deleted proteins have also been validated as potential targets for the prevention of HCC development. In this review, we summarize the clinical and molecular implications of HBV pre-S gene deletions and pre-S deleted proteins in HCC development and recurrence and highlight their potential applications in HCC prevention and therapy.

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Deep Sequencing Analysis of Hepatitis B Virus Quasispecies Characteristics in the Pre-S Region Prior to Development of Hepatocellular Carcinoma

Journal of Hepatology ◽

10.1016/s0168-8278(16)00524-9 ◽

2016 ◽

Vol 64 (2) ◽

pp. S357

Author(s):

D.K.H. Wong ◽

A.-Y. Zhang ◽

C.-L. Lai ◽

F.-Y. Huang ◽

W.-K. Seto ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Deep Sequencing ◽

Sequencing Analysis ◽

B Virus ◽

Deep Sequencing Analysis

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Comparison of the Characteristics of Hepatitis B Virus Whole Genomes Derived From Patients With Hepatocellular Carcinoma and Chronic Hepatitis B Infection

10.21203/rs.3.rs-41025/v1 ◽

2020 ◽

Author(s):

Shuang Zhang ◽

Feng Wang ◽

He Liu ◽

Qiudong Su ◽

Feng Qiu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Public Health Problem ◽

Full Length ◽

Serum Samples ◽

Hbv Genotypes ◽

B Virus

Abstract Background: Hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV) infection is a serious public health problem in China. The aims of the present study was to report HCC prevalence in China and characterize the whole gene sequences of HBV derived from patients diagnosed with HCC as well as those with chronic hepatitis B (CHB) infections.Methods: Patients in the HCC group and the CHB group were recruited from national HBV surveillance sites, which were matched by age, gender, and region. All serum samples were tested for serological markers. Polymerase chain reaction (PCR) was used to amplify the HBV complete genome sequences. Then the analysis of the full-length HBV genomes was performed with bioinformatics and statistical software.Results: Serum samples were collected from 51 patients with HBV-related HCC and 76 patients with CHB. All patients were from six provinces (Guangxi, Hebei, Henan, Hunan, Qinghai, and Shanghai) in China. Sequencing and analysis of the full-length HBV genomes revealed the presence of four genotypes (B, C, CD, and I). The distribution of HBV genotypes and the positivity rate of the hepatitis B e antigen differed between the two groups. A total of 148 substitution sites deemed statistically significant were identified between the HCC and CHB groups. In addition, three mutational sites associated with HCC, (F22I/L/P in the pre-S2 region, P33S/T and S144A/T/V in the X region) were identified. Deletions to the pre-S and X regions were found in both HCC and CHB patients. However, deletions to the X region were more common in the HCC group than the CHB group.Conclusions: In this study the hotspot mutations associated with high risk of HCC mostly occurred in the sequences and some substitutions (C1470A/T, T1803A/G, and C1804T) that have not been previously reported. It was implicated that aa33 and aa144 substitution in X region may be new predictive markers for HCC. The results of our study would provide important basic information for HCC prevention.

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