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Total Hepatitis B Core Antigen Antibody, a Quantitative Non-Invasive Marker of Hepatitis B Virus Induced Liver Disease.

Yuan Q, Song LW, Cavallone D, Moriconi F, Cherubini B, Colombatto P, Oliveri F, Coco BA, Ricco G, Bonino F, Shih JW, Xia NS, Brunetto MR - PLoS ONE (2015)

Bottom Line: Overall total-anti-HBc and IgM-anti-HBc correlated significantly (p<0.001, r=0.417).Total-anti-HBc declined significantly in CHB patients with response to Peg-IFN (p<0.001) and in NUC-treated patients (p<0.001); the lowest levels (median 2.68, range 2.12-3.08 Log10 IU/ml) were found in long-term responders who cleared HBsAg subsequently.Total-anti-HBc qualifies as a useful marker of HBV-induced-liver-disease that might help to discriminate major phases of chronic HBV infection and to predict sustained response to antivirals.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China.

ABSTRACT
Non invasive immunologic markers of virus-induced liver disease are unmet needs. We tested the clinical significance of quantitative total and IgM-anti-HBc in well characterized chronic-HBsAg-carriers. Sera (212) were obtained from 111 HBsAg-carriers followed-up for 52 months (28-216) during different phases of chronic-HBV-genotype-D-infection: 10 HBeAg-positive, 25 inactive-carriers (HBV-DNA≤2000IU/ml, ALT<30U/L), 66 HBeAg-negative-CHB-patients and 10 with HDV-super-infection. In 35 patients treated with Peg-IFN±nucleos(t)ide-analogues (NUCs) sera were obtained at baseline, end-of-therapy and week-24-off-therapy and in 22 treated with NUCs (for 60 months, 42-134m) at baseline and end-of-follow-up. HBsAg and IgM-anti-HBc were measured by Architect-assays (Abbott, USA); total-anti-HBc by double-antigen-sandwich-immune-assay (Wantai, China); HBV-DNA by COBAS-TaqMan (Roche, Germany). Total-anti-HBc were detectable in all sera with lower levels in HBsAg-carriers without CHB (immune-tolerant, inactive and HDV-superinfected, median 3.26, range 2.26-4.49 Log10 IU/ml) versus untreated-CHB (median 4.68, range 2.76-5.54 Log10 IU/ml), p<0.0001. IgM-anti-HBc positive using the chronic-hepatitis-cut-off" (0.130-S/CO) were positive in 102 of 212 sera (48.1%). Overall total-anti-HBc and IgM-anti-HBc correlated significantly (p<0.001, r=0.417). Total-anti-HBc declined significantly in CHB patients with response to Peg-IFN (p<0.001) and in NUC-treated patients (p<0.001); the lowest levels (median 2.68, range 2.12-3.08 Log10 IU/ml) were found in long-term responders who cleared HBsAg subsequently. During spontaneous and therapy-induced fluctuations of CHB (remissions and reactivations) total- and IgM-anti-HBc correlated with ALT (p<0.001, r=0.351 and p=0.008, r=0.185 respectively). Total-anti-HBc qualifies as a useful marker of HBV-induced-liver-disease that might help to discriminate major phases of chronic HBV infection and to predict sustained response to antivirals.

No MeSH data available.


Related in: MedlinePlus

Receiver operating characteristic (ROC) curve analyses.Total-anti-HBc (full line) and anti-HBc-IgM (dotted line). A. AUROCs of total-anti-HBc and IgM-anti-HBc to identify IC from CHB were 0.947 (95% CI 0.86–0.97, p<0.0001) and 0.915 (95% CI 0.91–0.99, p<0.0001) respectively. B. AUROCs of total-anti-HBc and IgM-anti-HBc to identify HBeAg-negative-CHB with SVR from untreated HBeAg-negative-CHB were 0.928 (95% CI 0.89–0.97, p<0.0001) and 0.871 (95% CI 0.81–0.93, p<0.0001). The discriminative capacity of the 2 assays was comparable, even if total-anti-HBc performed better than IgM-anti-HBc (p = 0.212 and p = 0.062 for ROC analysis a and b respectively). We identified 2 cut-off-values for total-anti-HBc: the former (12489IU/ml) to distinguish IC from HBeAg-negative-CHB with 81.8%-sensitivity, 94.4%-specificity, 76.1%-PPV, 96.4%-NPVs and 87.3%-DA, the latter (10804IU/ml) to distinguish HBeAg-negative-CHB with SVR from untreated patients with 83.3%-sensitivity, 88.6%-specificity,84.9%-PPV, 87.3%-NPV and 86.0%-DA.
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pone.0130209.g002: Receiver operating characteristic (ROC) curve analyses.Total-anti-HBc (full line) and anti-HBc-IgM (dotted line). A. AUROCs of total-anti-HBc and IgM-anti-HBc to identify IC from CHB were 0.947 (95% CI 0.86–0.97, p<0.0001) and 0.915 (95% CI 0.91–0.99, p<0.0001) respectively. B. AUROCs of total-anti-HBc and IgM-anti-HBc to identify HBeAg-negative-CHB with SVR from untreated HBeAg-negative-CHB were 0.928 (95% CI 0.89–0.97, p<0.0001) and 0.871 (95% CI 0.81–0.93, p<0.0001). The discriminative capacity of the 2 assays was comparable, even if total-anti-HBc performed better than IgM-anti-HBc (p = 0.212 and p = 0.062 for ROC analysis a and b respectively). We identified 2 cut-off-values for total-anti-HBc: the former (12489IU/ml) to distinguish IC from HBeAg-negative-CHB with 81.8%-sensitivity, 94.4%-specificity, 76.1%-PPV, 96.4%-NPVs and 87.3%-DA, the latter (10804IU/ml) to distinguish HBeAg-negative-CHB with SVR from untreated patients with 83.3%-sensitivity, 88.6%-specificity,84.9%-PPV, 87.3%-NPV and 86.0%-DA.

Mentions: Overall total-anti-HBc and IgM-anti-HBc correlated significantly (p<0.001, r = 0.417) and both total-anti-HBc and IgM-anti-HBc correlated with ALT p<0.001, r = 0.351 and p = 0.008, r = 0.185 respectively. Using total-anti-HBc and IgM-anti-HBc as binary classifiers we ran two ROC curves separating: A) Inactive carriers (IC) from chronic-hepatitis-B (CHB) patients (Fig 2a: AUROC of 0.947 (95% CI 0.86–0.97, p<0.0001) for total-anti-HBc and 0.915 (95% CI 0.91–0.99, p<0.0001) for IgM-anti-HBc; B) Treated HBeAg-negative-CHB with SVR from untreated HBeAg-negative-CHB (Fig 2b: AUROCs of 0.947 (95% CI 0.86–0.97, p<0.0001) for total-anti-HBc and 0.915 (95% CI 0.91–0.99, p<0.0001) for IgM-anti-HBc.


Total Hepatitis B Core Antigen Antibody, a Quantitative Non-Invasive Marker of Hepatitis B Virus Induced Liver Disease.

Yuan Q, Song LW, Cavallone D, Moriconi F, Cherubini B, Colombatto P, Oliveri F, Coco BA, Ricco G, Bonino F, Shih JW, Xia NS, Brunetto MR - PLoS ONE (2015)

Receiver operating characteristic (ROC) curve analyses.Total-anti-HBc (full line) and anti-HBc-IgM (dotted line). A. AUROCs of total-anti-HBc and IgM-anti-HBc to identify IC from CHB were 0.947 (95% CI 0.86–0.97, p<0.0001) and 0.915 (95% CI 0.91–0.99, p<0.0001) respectively. B. AUROCs of total-anti-HBc and IgM-anti-HBc to identify HBeAg-negative-CHB with SVR from untreated HBeAg-negative-CHB were 0.928 (95% CI 0.89–0.97, p<0.0001) and 0.871 (95% CI 0.81–0.93, p<0.0001). The discriminative capacity of the 2 assays was comparable, even if total-anti-HBc performed better than IgM-anti-HBc (p = 0.212 and p = 0.062 for ROC analysis a and b respectively). We identified 2 cut-off-values for total-anti-HBc: the former (12489IU/ml) to distinguish IC from HBeAg-negative-CHB with 81.8%-sensitivity, 94.4%-specificity, 76.1%-PPV, 96.4%-NPVs and 87.3%-DA, the latter (10804IU/ml) to distinguish HBeAg-negative-CHB with SVR from untreated patients with 83.3%-sensitivity, 88.6%-specificity,84.9%-PPV, 87.3%-NPV and 86.0%-DA.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482637&req=5

pone.0130209.g002: Receiver operating characteristic (ROC) curve analyses.Total-anti-HBc (full line) and anti-HBc-IgM (dotted line). A. AUROCs of total-anti-HBc and IgM-anti-HBc to identify IC from CHB were 0.947 (95% CI 0.86–0.97, p<0.0001) and 0.915 (95% CI 0.91–0.99, p<0.0001) respectively. B. AUROCs of total-anti-HBc and IgM-anti-HBc to identify HBeAg-negative-CHB with SVR from untreated HBeAg-negative-CHB were 0.928 (95% CI 0.89–0.97, p<0.0001) and 0.871 (95% CI 0.81–0.93, p<0.0001). The discriminative capacity of the 2 assays was comparable, even if total-anti-HBc performed better than IgM-anti-HBc (p = 0.212 and p = 0.062 for ROC analysis a and b respectively). We identified 2 cut-off-values for total-anti-HBc: the former (12489IU/ml) to distinguish IC from HBeAg-negative-CHB with 81.8%-sensitivity, 94.4%-specificity, 76.1%-PPV, 96.4%-NPVs and 87.3%-DA, the latter (10804IU/ml) to distinguish HBeAg-negative-CHB with SVR from untreated patients with 83.3%-sensitivity, 88.6%-specificity,84.9%-PPV, 87.3%-NPV and 86.0%-DA.
Mentions: Overall total-anti-HBc and IgM-anti-HBc correlated significantly (p<0.001, r = 0.417) and both total-anti-HBc and IgM-anti-HBc correlated with ALT p<0.001, r = 0.351 and p = 0.008, r = 0.185 respectively. Using total-anti-HBc and IgM-anti-HBc as binary classifiers we ran two ROC curves separating: A) Inactive carriers (IC) from chronic-hepatitis-B (CHB) patients (Fig 2a: AUROC of 0.947 (95% CI 0.86–0.97, p<0.0001) for total-anti-HBc and 0.915 (95% CI 0.91–0.99, p<0.0001) for IgM-anti-HBc; B) Treated HBeAg-negative-CHB with SVR from untreated HBeAg-negative-CHB (Fig 2b: AUROCs of 0.947 (95% CI 0.86–0.97, p<0.0001) for total-anti-HBc and 0.915 (95% CI 0.91–0.99, p<0.0001) for IgM-anti-HBc.

Bottom Line: Overall total-anti-HBc and IgM-anti-HBc correlated significantly (p<0.001, r=0.417).Total-anti-HBc declined significantly in CHB patients with response to Peg-IFN (p<0.001) and in NUC-treated patients (p<0.001); the lowest levels (median 2.68, range 2.12-3.08 Log10 IU/ml) were found in long-term responders who cleared HBsAg subsequently.Total-anti-HBc qualifies as a useful marker of HBV-induced-liver-disease that might help to discriminate major phases of chronic HBV infection and to predict sustained response to antivirals.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China.

ABSTRACT
Non invasive immunologic markers of virus-induced liver disease are unmet needs. We tested the clinical significance of quantitative total and IgM-anti-HBc in well characterized chronic-HBsAg-carriers. Sera (212) were obtained from 111 HBsAg-carriers followed-up for 52 months (28-216) during different phases of chronic-HBV-genotype-D-infection: 10 HBeAg-positive, 25 inactive-carriers (HBV-DNA≤2000IU/ml, ALT<30U/L), 66 HBeAg-negative-CHB-patients and 10 with HDV-super-infection. In 35 patients treated with Peg-IFN±nucleos(t)ide-analogues (NUCs) sera were obtained at baseline, end-of-therapy and week-24-off-therapy and in 22 treated with NUCs (for 60 months, 42-134m) at baseline and end-of-follow-up. HBsAg and IgM-anti-HBc were measured by Architect-assays (Abbott, USA); total-anti-HBc by double-antigen-sandwich-immune-assay (Wantai, China); HBV-DNA by COBAS-TaqMan (Roche, Germany). Total-anti-HBc were detectable in all sera with lower levels in HBsAg-carriers without CHB (immune-tolerant, inactive and HDV-superinfected, median 3.26, range 2.26-4.49 Log10 IU/ml) versus untreated-CHB (median 4.68, range 2.76-5.54 Log10 IU/ml), p<0.0001. IgM-anti-HBc positive using the chronic-hepatitis-cut-off" (0.130-S/CO) were positive in 102 of 212 sera (48.1%). Overall total-anti-HBc and IgM-anti-HBc correlated significantly (p<0.001, r=0.417). Total-anti-HBc declined significantly in CHB patients with response to Peg-IFN (p<0.001) and in NUC-treated patients (p<0.001); the lowest levels (median 2.68, range 2.12-3.08 Log10 IU/ml) were found in long-term responders who cleared HBsAg subsequently. During spontaneous and therapy-induced fluctuations of CHB (remissions and reactivations) total- and IgM-anti-HBc correlated with ALT (p<0.001, r=0.351 and p=0.008, r=0.185 respectively). Total-anti-HBc qualifies as a useful marker of HBV-induced-liver-disease that might help to discriminate major phases of chronic HBV infection and to predict sustained response to antivirals.

No MeSH data available.


Related in: MedlinePlus