Table 1.
Characteristics of HBsAg Carriers.
Fig 1.
Serum levels of total-anti-HBc (a) and anti-HBc-IgM (b) in 4 groups: a) inactive HBsAg-carriers; b) untreated HBeAg-negative-CHB patients, baseline; c) HBeAg-negative-CHB patients with SVR to Peg-IFN±NUC (EOF); d) NUC-treated patients (EOF). The distribution of total-anti-HBc levels falls within the dynamic range of quantification of the assay in all the patients. On the contrary, this holds true for 52% only of the sera, even using the lower CHB cut-off of 0.130 S/CO.
Fig 2.
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.
Fig 3.
Kinetics of HBV markers in patients treated with Peg-IFN.
Kinetics of median values of HBV markers between baseline (BL), end of therapy (EOT) and end of follow-up (EOF) in 35 patients treated with Peg-IFN: 6 NR, 10 REL and 19 SVR. Patients who did not respond to IFN (NR and REL) were subsequently switched to NUC. P values: a) HBsAg: BL vs EOT 0.27 for NR, 0.50 for REL and <0.001 for SVR; b) HBV-DNA: BL vs EOT 0.59 for NR, 0.014 for REL and <0.001 for SVR; c) Anti-HBc-IgM: BL vs EOT 0.24 for NR, 0.01 for REL and 0.17 for SVR; d) Total Anti-HBc: BL vs EOT 0.39 for NR, <0.001 for REL and <0.001 for SVR.
Fig 4.
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.