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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

Kinetics of ALT and HBV markers between between remission and reactivation phases of CHB.A. untreated HBeAg-negative CHB patients at spontaneous disease remissions and flare-ups (5 cases): total-anti-HBc mean 4.23, median 4.56, and mean 4.88, median 4.93-Log10IU/ml, p = 0.054; IgM-anti-HBc mean 0.24, median 0.25, and mean 1.35, median 1.0S/CO, p = 0.054; HBV-DNA mean 3.78, median 3.76, and mean 5.86, median 5.89-Log10IU/ml, p = 0.058; HBsAg mean 3.18, median 3.4, and mean 3.21, median 3.52-Log10IU/ml, p = 0.91and ALT mean 23, median 23, and mean 244.6, median 201UI/L, p = 0.046. B. CHB patients treated with PEG-IFN (REL) at the time of temporary disease remission during therapy and hepatitis reactivation after relapse (9 cases): total-anti-HBc mean 4.04, median 4.01, and mean 4.79, median-4.93-Log10IU/ml, p = 0.002; IgM-anti-HBc mean 0.39, median 0.14, and mean 1.16, median 0.81S/CO, p = 0.03; HBV-DNA mean 3.34, median 1.74, and mean 7.18, median 7.27-Log10IU/ml, p = 0.004; HBsAg mean 3.61, median 3.54, and mean 3.55, median 3.65-Log10IU/ml, p = 0.73 and ALT mean 43, median 29, and mean 413, median 311 UI/L, p = 0.007.
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pone.0130209.g004: Kinetics of ALT and HBV markers between between remission and reactivation phases of CHB.A. untreated HBeAg-negative CHB patients at spontaneous disease remissions and flare-ups (5 cases): total-anti-HBc mean 4.23, median 4.56, and mean 4.88, median 4.93-Log10IU/ml, p = 0.054; IgM-anti-HBc mean 0.24, median 0.25, and mean 1.35, median 1.0S/CO, p = 0.054; HBV-DNA mean 3.78, median 3.76, and mean 5.86, median 5.89-Log10IU/ml, p = 0.058; HBsAg mean 3.18, median 3.4, and mean 3.21, median 3.52-Log10IU/ml, p = 0.91and ALT mean 23, median 23, and mean 244.6, median 201UI/L, p = 0.046. B. CHB patients treated with PEG-IFN (REL) at the time of temporary disease remission during therapy and hepatitis reactivation after relapse (9 cases): total-anti-HBc mean 4.04, median 4.01, and mean 4.79, median-4.93-Log10IU/ml, p = 0.002; IgM-anti-HBc mean 0.39, median 0.14, and mean 1.16, median 0.81S/CO, p = 0.03; HBV-DNA mean 3.34, median 1.74, and mean 7.18, median 7.27-Log10IU/ml, p = 0.004; HBsAg mean 3.61, median 3.54, and mean 3.55, median 3.65-Log10IU/ml, p = 0.73 and ALT mean 43, median 29, and mean 413, median 311 UI/L, p = 0.007.

Mentions: Finally we studied the dynamic variations of ALT and HBV markers in 18 paired sera from 9 REL after Peg-IFN at the time of their on-treatment disease remission and hepatitis-B-relapse after treatment discontinuation and in 10 paired sera from 5 untreated HBeAg-negative-CHB patients with spontaneous remissions and reactivations. In Peg-IFN-REL all biomarkers showed statistically significant variations, but HBsAg, whereas in untreated patients only ALT variations were statistically significant whereas for total-anti-HBc, IgM anti-HBc and HBV-DNA there was a trend to significance (Fig 4).


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)

Kinetics of ALT and HBV markers between between remission and reactivation phases of CHB.A. untreated HBeAg-negative CHB patients at spontaneous disease remissions and flare-ups (5 cases): total-anti-HBc mean 4.23, median 4.56, and mean 4.88, median 4.93-Log10IU/ml, p = 0.054; IgM-anti-HBc mean 0.24, median 0.25, and mean 1.35, median 1.0S/CO, p = 0.054; HBV-DNA mean 3.78, median 3.76, and mean 5.86, median 5.89-Log10IU/ml, p = 0.058; HBsAg mean 3.18, median 3.4, and mean 3.21, median 3.52-Log10IU/ml, p = 0.91and ALT mean 23, median 23, and mean 244.6, median 201UI/L, p = 0.046. B. CHB patients treated with PEG-IFN (REL) at the time of temporary disease remission during therapy and hepatitis reactivation after relapse (9 cases): total-anti-HBc mean 4.04, median 4.01, and mean 4.79, median-4.93-Log10IU/ml, p = 0.002; IgM-anti-HBc mean 0.39, median 0.14, and mean 1.16, median 0.81S/CO, p = 0.03; HBV-DNA mean 3.34, median 1.74, and mean 7.18, median 7.27-Log10IU/ml, p = 0.004; HBsAg mean 3.61, median 3.54, and mean 3.55, median 3.65-Log10IU/ml, p = 0.73 and ALT mean 43, median 29, and mean 413, median 311 UI/L, p = 0.007.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0130209.g004: Kinetics of ALT and HBV markers between between remission and reactivation phases of CHB.A. untreated HBeAg-negative CHB patients at spontaneous disease remissions and flare-ups (5 cases): total-anti-HBc mean 4.23, median 4.56, and mean 4.88, median 4.93-Log10IU/ml, p = 0.054; IgM-anti-HBc mean 0.24, median 0.25, and mean 1.35, median 1.0S/CO, p = 0.054; HBV-DNA mean 3.78, median 3.76, and mean 5.86, median 5.89-Log10IU/ml, p = 0.058; HBsAg mean 3.18, median 3.4, and mean 3.21, median 3.52-Log10IU/ml, p = 0.91and ALT mean 23, median 23, and mean 244.6, median 201UI/L, p = 0.046. B. CHB patients treated with PEG-IFN (REL) at the time of temporary disease remission during therapy and hepatitis reactivation after relapse (9 cases): total-anti-HBc mean 4.04, median 4.01, and mean 4.79, median-4.93-Log10IU/ml, p = 0.002; IgM-anti-HBc mean 0.39, median 0.14, and mean 1.16, median 0.81S/CO, p = 0.03; HBV-DNA mean 3.34, median 1.74, and mean 7.18, median 7.27-Log10IU/ml, p = 0.004; HBsAg mean 3.61, median 3.54, and mean 3.55, median 3.65-Log10IU/ml, p = 0.73 and ALT mean 43, median 29, and mean 413, median 311 UI/L, p = 0.007.
Mentions: Finally we studied the dynamic variations of ALT and HBV markers in 18 paired sera from 9 REL after Peg-IFN at the time of their on-treatment disease remission and hepatitis-B-relapse after treatment discontinuation and in 10 paired sera from 5 untreated HBeAg-negative-CHB patients with spontaneous remissions and reactivations. In Peg-IFN-REL all biomarkers showed statistically significant variations, but HBsAg, whereas in untreated patients only ALT variations were statistically significant whereas for total-anti-HBc, IgM anti-HBc and HBV-DNA there was a trend to significance (Fig 4).

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