肝癌的发展前乙型肝炎病毒剪接增

StephenW

Hepatitis B virus splicing is enhanced prior to development of hepatocellular carcinoma

    Julianne Bayliss a, Corresponding author contact information, E-mail the corresponding author,
    Lucy Lim a, b,
    Alexander J.V. Thompson a, c,
    Paul Desmond c,
    Peter Angus b,
    Stephen Locarnini a,
    Peter A Revill a

    a Division of Molecular Research and Development, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria 3051, Australia
    b Department of Gastroenterology, Austin Hospital, Heidelberg, Victoria 3084, Australia
    c Department of Gastroenterology, St Vincent’s Hospital, Fitzroy 3065, Victoria, Australia

Abstract
Background & aims

The hepatitis B virus (HBV) genome encodes specific sequence elements which promote splicing of viral DNA. It has been previously suggested that spliced HBV (spHBV) variants promote viral replication and protein production, leading to hepatocellular carcinoma (HCC). In this study we have analysed changes in spHBV over time; providing the first longitudinal analysis of spHBV in relation to the development of HCC.
Methods

Serial serum samples were collected from 165 patients with chronic HBV monoinfection, including 58 patients who later developed HCC. Real time PCR was used to amplify and quantify wt and sp DNA loads.
Results

spHBV was detected in over 80% of patients with chronic HBV infection. Median serum spHBV levels were significantly higher in HCC patients than HCC-free control patients (p< 0.001). Univariate analysis revealed a strong correlation between time to HCC diagnosis and spHBV DNA levels (τ= 0.203; p= 0.016). Asian HBV genotype (p= 0.025) and increased viral load (p< 0.001) were also significantly associated with increased spHBV DNA levels. Multiple regression analysis revealed time to diagnosis of HCC, Asian HBV genotypes and viral load to be associated with increased spHBV DNA (model p< 0.001; R2= 0.189).
Conclusions

HBV splicing is a common event during chronic infection and increases prior to diagnosis of HCC. Measurement of HBV splicing may prove a valuable adjunct to be used in the identification of chronically infected patients who are at increased risk of developing HCC.

StephenW

B型肝炎病毒（HBV）的基因组编码促进剪接的病毒DNA的特定序列中的元素。它先前已建议，拼接的HBV（spHBV）变种促进病毒的复制和蛋白质的生产，导致肝细胞癌（HCC）。在本研究中，我们已经分析了随着时间的推移变化spHBV提供所述第一纵向分析spHBV的发展为肝细胞癌有关。
方法

串行血清样品分别采自慢性HBV单一感染165例，包括58例患者，后来开发的肝癌。采用实时PCR扩增和定量重量和SP DNA载量。
结果

spHBV在80％以上的患者与慢性乙肝病毒感染检测。中位数血清spHBV水平显着高于肝癌患者肝癌的对照组患者（P <0.001）。单因素分析显示很强的相关性之间的时间来肝癌诊断和spHBV的DNA水平（τ= 0.203，P = 0.016）。亚洲HBV基因型（P = 0.025）和病毒载量的增加（P <0.001）与的增加spHBV DNA水平也显着相关。多元回归分析显示，亚洲的时间来诊断肝癌，HBV基因型和病毒载量与：增加spHBV DNA（型号为P <0.001，R2 = 0.189）相关。
结论

HBV拼接是一种常见的发生在慢性感染，并增加前诊断为肝癌。 HBV拼接测量可能被证明有价值的辅助可用于识别慢性感染的患者发展为HCC的风险增加。