HBcrAg predicts hepatocellular carcinoma development: An analysis using time-dependent receiver operating characteristics

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• 作者：Toshifumi Tada¹ ; ^{tadat0627@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Takashi Kumada¹ ; Hidenori Toyoda¹ ; Seiki Kiriyama¹ ; Makoto Tanikawa¹ ; Yasuhiro Hisanaga¹ ; Akira Kanamori¹ ; Shusuke Kitabatake¹ ; Tsuyoki Yama¹ ; Junko Tanaka²
• 关键词：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
• 刊名：Journal of Hepatology
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：65
• 期：1
• 页码：48-56
• 全文大小：910 K

文摘

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.