TY - JOUR
T1 - Incremental value of HBcrAg to classify 1582 HBeAg-negative individuals in chronic infection without liver disease or hepatitis
AU - Brunetto, MR
AU - Carey, I
AU - Maasoumy, B
AU - Marcos-Fosch, C
AU - Boonstra, Andre
AU - Caviglia, GP
AU - Loglio, A
AU - Cavallone, D
AU - Scholtes, C
AU - Ricco, G
AU - Smedile, A
AU - Riveiro-Barciela, M
AU - van Bommel, F
AU - Baltissen - van der Eijk, Annemiek
AU - Zoulim, F
AU - Berg, Thomas
AU - Cornberg, M
AU - Lampertico, P
AU - Agarwal, K
AU - Buti, M
PY - 2021/3
Y1 - 2021/3
N2 - Background: An accurate, single-point differential diagnosis between HBeAg-negative infection (ENI) and chronic hepatitis B (CHB) is an unmet need. Aims: To assess the diagnostic value of the new hepatitis B core-related antigen (HBcrAg) assay. Methods: A retrospective anonymised data analysis was performed in a multicentre European (nine centres and six countries) cohort of 1582 consecutive HBsAg-positive/HBeAg-negative subjects classified according to EASL guidelines as: 550-CHB, 710-ENI and 322-GZ (grey-zone, HBV-DNA <20 000 IU/mL). Results: Mean age was 44 (±13.2 y), 59% were men; HBV genotypes were 15% A, 2% B, 2% C, 45% D, 9% E, 1% F and 26% unknown. Median HBV-DNA serum levels were 2.2 (1.5-2.7), 3.5 (3.2-3.8) and 5.6 (4.8-6.6) logIU/mL in ENI, GZ and CHB, P < 0.0001. HBsAg serum levels (HBsAgsl) were comparable in CHB and GZ, but lower in ENI (2.9 [2.1-3.6] logIU/mL), P < 0.0001. HBcrAg serum levels (HBcrAgsl) were <3 logU/mL in 90.7% (644/710) ENI, 75.2% (242/322) GZ and 4.7% (26/550) CHB (P < 0.0001). Median HBcrAgsl were 4.8 (3.9-5.7), 2.5 (2.0-2.9) and 2.0 (2.0-2.5) logU/mL in CHB, GZ and ENI, (P < 0.0001). ROC-AUCs for HBcrAg and HBsAg were 0.968 (95% CI, 0.958-0.977) and 0.732 (95% CI, 0.704-0.760) respectively. The optimal HBcrAgsl cut-off to distinguish CHB from ENI was 3.14 logU/mL (95% CI, 3.02-3.25, 91% SE, 93% SP and 92.4% DA). HBcrAgsl were associated with HBV genotypes (P < 0.001, one-way ANOVA) but using genotype-specific cut-offs, HBcrAg DA remained unchanged with overlapping 95% CI. Conclusion: The HBcrAg assay showed high diagnostic performance in the accurate single-point identification of patients with HBeAg-negative CHB, independently of HBV genotype. This should prompt future prospective studies to confirm its diagnostic role in clinical practice.
AB - Background: An accurate, single-point differential diagnosis between HBeAg-negative infection (ENI) and chronic hepatitis B (CHB) is an unmet need. Aims: To assess the diagnostic value of the new hepatitis B core-related antigen (HBcrAg) assay. Methods: A retrospective anonymised data analysis was performed in a multicentre European (nine centres and six countries) cohort of 1582 consecutive HBsAg-positive/HBeAg-negative subjects classified according to EASL guidelines as: 550-CHB, 710-ENI and 322-GZ (grey-zone, HBV-DNA <20 000 IU/mL). Results: Mean age was 44 (±13.2 y), 59% were men; HBV genotypes were 15% A, 2% B, 2% C, 45% D, 9% E, 1% F and 26% unknown. Median HBV-DNA serum levels were 2.2 (1.5-2.7), 3.5 (3.2-3.8) and 5.6 (4.8-6.6) logIU/mL in ENI, GZ and CHB, P < 0.0001. HBsAg serum levels (HBsAgsl) were comparable in CHB and GZ, but lower in ENI (2.9 [2.1-3.6] logIU/mL), P < 0.0001. HBcrAg serum levels (HBcrAgsl) were <3 logU/mL in 90.7% (644/710) ENI, 75.2% (242/322) GZ and 4.7% (26/550) CHB (P < 0.0001). Median HBcrAgsl were 4.8 (3.9-5.7), 2.5 (2.0-2.9) and 2.0 (2.0-2.5) logU/mL in CHB, GZ and ENI, (P < 0.0001). ROC-AUCs for HBcrAg and HBsAg were 0.968 (95% CI, 0.958-0.977) and 0.732 (95% CI, 0.704-0.760) respectively. The optimal HBcrAgsl cut-off to distinguish CHB from ENI was 3.14 logU/mL (95% CI, 3.02-3.25, 91% SE, 93% SP and 92.4% DA). HBcrAgsl were associated with HBV genotypes (P < 0.001, one-way ANOVA) but using genotype-specific cut-offs, HBcrAg DA remained unchanged with overlapping 95% CI. Conclusion: The HBcrAg assay showed high diagnostic performance in the accurate single-point identification of patients with HBeAg-negative CHB, independently of HBV genotype. This should prompt future prospective studies to confirm its diagnostic role in clinical practice.
UR - http://www.scopus.com/inward/record.url?scp=85099602287&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/apt.16258
DO - https://doi.org/10.1111/apt.16258
M3 - Article
VL - 53
SP - 733
EP - 744
JO - Alimentary Pharmacology and Therapeutics
JF - Alimentary Pharmacology and Therapeutics
SN - 0269-2813
IS - 6
ER -
