HBcrAg预测肝癌发展：使用时间依赖性受试者工作特征分析

StephenW

HBcrAg predicts hepatocellular carcinoma development: An analysis using time-dependent receiver operating characteristics
Toshifumi Tadacorrespondenceemail
, Takashi Kumada
, Hidenori Toyoda
, Seiki Kiriyama
, Makoto Tanikawa
, Yasuhiro Hisanaga
, Akira Kanamori
, Shusuke Kitabatake
, Tsuyoki Yama
, Junko Tanaka
Article has an altmetric score of 17
DOI: http://dx.doi.org/10.1016/j.jhep.2016.03.013 |

Background & Aims

Several hepatitis B virus (HBV) markers have been identified as factors associated with the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We clarified the predictive power of HBV markers for the development of HCC using receiver operating characteristic (ROC) analysis with a consideration of time dependence.
Methods

A total of 1031 CHB patients who were not treated with nucleos(t)ide analogue therapy were enrolled. Univariate, multivariate, and time-dependent ROC curves for HBV markers associated with the development of HCC were analyzed.
Results

Seventy-eight patients developed HCC during the follow-up period (median duration 10.7 years). Different levels or statuses of several HBV markers (HBV genotype, HBV DNA, HBV core-related antigen (HBcrAg), hepatitis B e antigen (HBeAg), and basal core promoter (BCP)), but not hepatitis B surface antigen, were significantly associated with the incidence of HCC by univariate analysis using the log-rank test. Cox proportional hazards models using the covariates of HBV genotype status, HBV DNA levels, HBcrAg levels, HBeAg status, and BCP status indicated that HBcrAg >2.9 log U/ml (hazard ratio (HR), 5.05; 95% confidence interval (CI), 2.40–10.63) and BCP mutation (HR, 28.85; 95% CI, 4.00–208.20) were independently associated with the incidence of HCC. Additionally, time-dependent ROC analysis showed that HBcrAg was superior to HBV DNA in terms of predictive power for HCC development throughout the follow-up period.
Conclusions

Elevation of HBcrAg levels in CHB patients is associated with the development of HCC. HBcrAg is an excellent predictor of HCC development.
Lay summary

Hepatitis B virus (HBV) core-related antigen (HBcrAg) is an excellent predictor of hepatocellular carcinoma (HCC) development in chronic hepatitis B patients without nucleos(t)ide analogue therapy. HBcrAg was superior to HBV DNA in terms of predictive power for HCC development by time-dependent receiver operating characteristic analysis.


Abbreviations:
CHB (chronic hepatitis B), HCC (hepatocellular carcinoma), HBsAg (hepatitis B surface antigen), HBV (hepatitis B virus), HBeAg (hepatitis B e antigen), BCP (basal core promoter), HBcrAg (hepatitis B virus core-related antigen), cccDNA (covalently closed circular DNA), NA (nucleos(t)ide analogue), ROC (receiver operating characteristic), AUC (area under the receiver operating characteristic curve), AFP (α-fetoprotein), CT (computed tomography), MRI (magnetic resonance imaging), HR (hazard ratio), CI (confidence interval), AST (aspartate aminotransferase), ALT (alanine aminotransferase), γ-GTP (gamma-glutamyl transpeptidase), ALP (alkaline phosphatase), IFN (interferon)
Keywords:
Hepatitis B, Hepatitis B virus core-related antigen, Hepatocellular carcinoma, Time-dependent receiver operating characteristic

StephenW

HBcrAg预测肝癌发展：使用时间依赖性受试者工作特征分析
敏文Tadacorrespondenceemail
，熊田隆
，丰田秀典
，精桐山
，诚谷川
中曾根久永
，金森晃
，周助Kitabatake
，Tsuyoki阎王
，田中顺子
文章中的17分altmetric
DOI：http://dx.doi.org/10.1016/j.jhep.2016.03.013 |

背景和目的

几个乙型肝炎病毒（HBV）标志物已被鉴定为肝癌的治疗慢性乙型肝炎（CHB）的开发（HCC）的相关的因素。我们阐明HBV标志物的预测能力，使用接收器与一个考虑的时间依赖性的操作特征（ROC）分析肝癌的发展。
方法

共有谁没有用核苷（酸）类似物IDE疗法治疗慢性乙型肝炎1031例患者。与肝癌的发展相关联的HBV标志物单因素，多变量，和时间依赖性ROC曲线进行分析。
结果

78例在随访期间（中位时间10.7年）开发的肝癌。不同级别或几种HBV标志物的状态（HBV基因型，HBV-DNA，HBV核心相关抗原（HBcrAg），乙型肝炎e抗原（HBeAg），和基底核心启动子（BCP）），但不乙肝表面抗原，均显著肝癌的通过使用对数秩检验单因素分析的发病相关联。采用HBV基因型状态，HBV DNA水平，HBcrAg水平，HBeAg状态和BCP状态协变量Cox比例风险模型表明，HBcrAg> 2.9日志单位/毫升（危险比（HR），5.05; 95％可信区间（CI） ，2.40-10.63）和BCP突变（HR，28.85; 95％CI，4.00-208.20）独立与肝癌的发生有关。此外，依赖于时间的ROC分析表明，在HBcrAg整个随访期间肝癌发展的预测能力方面明显优于HBV DNA。
结论

慢性乙型肝炎患者HBcrAg水平升高与肝癌的发生有关。 HBcrAg是HCC发展的一个很好的指标。
莱总结

乙型肝炎病毒（HBV）核心相关抗原（HBcrAg）是慢性乙型肝炎患者肝细胞癌（HCC）发展的一个很好的预测无核苷（酸）类似物IDE治疗。 HBcrAg优于HBV DNA通过时间依赖性受试者工作特征分析肝癌发展的预测能力方面。
缩写：
CHB（慢性乙型肝炎），肝癌（肝细胞癌），乙肝表面抗原（乙肝表面抗原），HBV（乙肝病毒），大三阳（乙肝e抗原），BCP（基础核心启动子），HBcrAg（乙肝病毒核心 - 相关抗原），cccDNA的（共价闭合环状DNA），NA（核苷（酸）的ide类似物），ROC（接收者操作特征），AUC（接收机操作特性曲线）下面积，AFP（α甲胎蛋白），CT（计算机断层摄影术），MRI（磁共振成像），HR（危险比），CI（置信区间），AST（天冬氨酸转氨酶），ALT（丙氨酸转氨酶），γ-GTP（γ-谷氨酰转），ALP（碱性磷酸酶）， IFN（干扰素）
关键词：
乙型肝炎，乙肝病毒核心相关抗原，肝细胞癌，与时间相关的接收器操作特性