Ann Lab Med.  2019 Jan;39(1):67-75. 10.3343/alm.2019.39.1.67.

Performance of Hepatitis B Core-Related Antigen Versus Hepatitis B Surface Antigen and Hepatitis B Virus DNA in Predicting HBeAg-positive and HBeAg-negative Chronic Hepatitis

• Zhang ZQ
• Wang YB
• Lu W
• Liu DP
• Shi BS
• Zhang XN
• Huang D
• Li XF
• Zhou XL
• Ding RR

• KMID: 2420273
• DOI: http://doi.org/10.3343/alm.2019.39.1.67

Abstract

BACKGROUND
We examined changes in hepatitis B core-related antigen (HBcrAg) during the four sequential phases of chronic hepatitis B virus (HBV) infection: hepatitis B e antigen (HBeAg)-positive chronic infection (EPCI) and hepatitis (EPCH), followed by HBeAg-negative chronic infection (ENCI) and hepatitis (ENCH). We compared the performance of serum HBcrAg, hepatitis B surface antigen (HBsAg), and HBV DNA in predicting EPCH and ENCH.
METHODS
We enrolled 492 consecutive patients: 49 with EPCI, 243 with EPCH, 101 with ENCI, and 99 with ENCH. HBcrAg was detected by chemiluminescent enzyme immunoassays. HBsAg and HBeAg were detected by chemiluminescent microparticle immunoassays. HBV DNA was detected by real-time PCR. Predictive performance of HBcrAg, HBsAg, and HBV DNA was evaluated using ROC curves.
RESULTS
Areas under ROC curves (AUCs) of HBcrAg, HBsAg, and HBV DNA for predicting EPCH were 0.738, 0.812, and 0.717, respectively; optimal cutoffs were ≤1.43×105 kU/mL, ≤1.89×104 IU/mL, and ≤3.97×107 IU/mL, with sensitivities and specificities of 66.3% and 77.6%, 65.0% and 93.9%, and 60.5% and 79.6%, respectively. AUCs of HBcrAg, HBsAg, and HBV DNA for predicting ENCH were 0.887, 0.581, and 0.978, respectively; optimal cutoffs were >26.8 kU/mL, >2.29×102 IU/mL, and >8.75×103 IU/mL, with sensitivities and specificities of 72.7% and 95.1%, 86.9% and 39.6%, and 89.9% and 92.1%, respectively.
CONCLUSIONS
HBsAg and HBV DNA were the best predictors of EPCH and ENCH, respectively. HBcrAg is an important surrogate marker for predicting EPCH and ENCH.

Keyword

Hepatitis B core-related antigen; Hepatitis B surface antigen; Hepatitis B virus DNA; Chronic hepatitis B; Performance

MeSH Terms

Area Under Curve
Biomarkers
DNA
Hepatitis B e Antigens
Hepatitis B Surface Antigens*
Hepatitis B virus*
Hepatitis B*
Hepatitis B, Chronic
Hepatitis*
Hepatitis, Chronic*
Humans
Immunoassay
Immunoenzyme Techniques
Real-Time Polymerase Chain Reaction
ROC Curve
Biomarkers
DNA
Hepatitis B Surface Antigens
Hepatitis B e Antigens

Figure

• 

  Fig. 1 Distribution of serum virological markers in the four phases of chronic HBV infection. (A) HBcrAg. (B) HBsAg. (C) HBeAg. (D) HBV DNA. The middle horizontal red line represents the median; the upper and lower horizontal red lines represent the quartiles.Abbreviations: HBcrAg, hepatitis B core-related antigen; HBsAg, hepatitis B surface antigen; HBeAg, hepatitis B e antigen; HBV DNA, hepatitis B virus DNA; HBV, hepatitis B virus; EPCI, HBeAg-positive chronic infection; EPCH, HBeAg-positive chronic hepatitis; ENCI, HBeAg-negative chronic infection; ENCH, HBeAg-negative chronic hepatitis.

• 

  Fig. 2 ROC curves and AUCs of serum virological markers for predicting EPCH and ENCH. (A) ROC curves for predicting EPCH. (B) ROC curves for predicting ENCH. (C) AUCs for predicting EPCH. (D) AUCs for predicting ENCH.*Z=2.072; P=0.0383; †Z=3.115; P=0.0018; ‡Z=7.168; P<0.0001; §Z=4.128; P<0.0001; ∥Z=9.837; P<0.0001.Abbreviations: HBcrAg, hepatitis B core-related antigen; HBsAg, hepatitis B surface antigen; HBeAg, hepatitis B e antigen; HBV DNA, hepatitis B virus DNA; AUC, area under ROC curve; SE, standard error; 95%CI, 95% confidence interval; EPCH, HBeAg-positive chronic hepatitis; ENCH, HBeAg-negative chronic hepatitis.

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