Table 1.
Characteristics of the studies included in the meta-analysis.
| Study | Country | Year | Patients (n) |
HBeAg (+/−) |
HBV Genotype |
Therapy | HBcrAg | HBsAg | HBV cccDNA |
r * p-Value |
r ** p-Value |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Wong DKA [27] |
China | 2007 | 54 | 17/37 | n.a. | No | 1180 (<1.0–9.0 × 105) kU/mL |
n.a. | 1.3 (<0.002–23.3) copies/cell |
r = 0.664 p < 0.001 |
n.a. |
| Suzuki F [28] |
Japan | 2009 | 44 | 16/28 | n.a. | No | 5.05 ± 1.62 Log U/mL e+: 6.53 ± 1.14 Log U/mL e−: 4.20 ± 1.18 Log U/mL |
n.a. n.a. n.a. |
4.46 ± 0.87 Log copies/mg e+: 4.88 ± 1.06 Log copies/mg e−: 4.23 ± 0.64 Log copies/mg |
n.a. r = 0.687 p = 0.003 r = 0.542 p = 0.003 |
n.a. n.a. n.a. |
| Hosaka T [29] |
Japan | 2010 | 55 A | 23/32 | C = 51 Other = 9 |
30 LAM 17 LAM + ADV 8 ETV |
5.0 (<3.0–> 6.8) Log U/mL |
n.a. | 4.2 (3.0–5.0) Log copies/µg B |
r = 0.479 p = 0.028 B |
n.a. |
| Chuaypen N [30] |
Thailand | 2016 | 46 | 46/0 | B = 5 C = 41 |
No | 8.1 (7.7–8.4) Log U/mL |
3.9 (3.7–4.1) Log IU/mL |
1.6 (1.2–1.9) copies/cEq |
r = 0.564 p = 0.001 |
r = 0.424 p = 0.020 |
| Wong DKA [31] |
China | 2017 | 138 | 77/61 | B = 40 C = 82 n.a. = 16 |
Baseline 1 year NAs 6–12 years NAs |
586 (1–1.1 × 107) kU/mL C |
3.3 (−1.3–5.9) Log IU/mL C |
1.1 (0.005–258) copies/cell C |
r = 0.70 p < 0.001 C |
r = 0.40 p < 0.001 C |
| Chen EQ [32] |
China | 2017 | 139 | 111/28 | B = 88 C = 51 |
No | 9.23 ± 2.86 Log U/mL |
4.15 ± 0.86 Log IU/mL |
7.33 ± 1.03 Log copies/106 cells |
r = 0.929 p < 0.001 |
r = 0.742 p < 0.001 |
| Chuaypen N [33] |
Thailand | 2018 | 121 D | 0/121 | B = 25 C = 96 |
No | R: 4.1 ± 1.3 Log U/mL NR: 4.4 ± 1.1 Log U/mL |
R: 3.2 ± 0.4 Log IU/mL NR: 3.6 ± 0.5 Log IU/mL |
R: 0.4 ± 0.9 Log copies/cEq NR: 0.4 ± 1.2 Log copies/cEq |
r = 0.393 p = 0.009 |
r = 0.040 p = 0.737 |
| Chen S [34] |
China | 2018 | 160 E | n.a. | n.a. | n.a. | 5.10 (1.96–8.50) Log U/mL |
250 (0.14–250) IU/mL |
n.a. |
r = 0.436 p < 0.001 F |
n.a. |
| Hasegawa K [35] |
Japan | 2018 | 126 G | n.a. | n.a. | Untreated, n = 57 (A) previous NAs, n = 69 (B) |
A: 3.0 (2.0–7.0) Log U/mL B: 4.1 (2.0–7.0) Log U/mL |
A: 1692.7 (0.05–91960.7) IU/mL B: 1050.0 (0.05–71583.0) IU/mL |
A: 3.0 (1.5–5.8) Log copies/µg B: 3.4 (1.7–4.8) Log copies/µg |
A: r = 0.67 p < 0.001 B: r = 0.38 p = 0.007 |
A: r = 0.59 p < 0.001 B: r = 0.32 p = 0.007 |
| Wang L [36] |
China | 2019 | 82 | 82/0 (A); 44/12 (B) |
n.a. | Baseline (A) 2 years NAs (B) |
A: 7.97 ± 0.96 Log U/mL B: 5.74 ± 1.10 Log U/mL |
A: 4.05 ± 0.64 Log IU/mL B: 3.32 ± 0.90 Log IU/mL |
A: 0.67 ± 0.74 Log copies/cell B: −0.94 ± 0.60 Log copies/cell |
A: r = 0.323 H p < 0.001 B: r = 0.108 p = 0.403 |
A: r = 0.152 p = 0.172 B: r = 0.39 p = 0.002 |
| Testoni B [23] |
France | 2019 | 130 | 36/94 | A = 20 B = 4 C = 13 D = 51 E = 14 F = 3 |
No | 5.3 (4.0–7.6) Log U/mL e+: 8 (7.3–8.3) Log U/mL e−: 4.0 (3.7–4.9) Log U/mL |
3.9 (3.4–4.3) Log IU/mL e+: 4.61 (4.1–5.2) Log IU/mL e−: 3.74 (3.2–4.1) Log IU/mL |
0.15 (0.06–1.34) copies/cell e+: 6.3 (1.4–18.1) copies/cell e−: 0.09 (0.03–0.2) copies/cell |
r = 0.74 p <0.001 I e+: r = 0.80 p <0.001 L e− CH: r = 0.25 p = n.s. I e− CI: r = 0.47 p = 0.05 I |
r = 0.26 p = 0.044 I e+: r = 0.33 p = 0.01 L e− CH: r = −0.4 p = 0.01 I e− CI: r = −0.03 p = n.s. I |
| Chen EQ [37] |
China | 2019 | 110 | 85/25 | B = 68 C = 42 |
No | e+: 10.30 (6.00–12.30) Log U/mL e−: 5.40 (3.28–7.20) Log U/mL |
e+: 4.59 (0.82–5.10) Log IU/mL e−: 3.49 (0.99–4.01) Log IU/mL |
e+: 7.46 (5.11–8.17) Log copies/106 cells e−: 6.03 (5.00–6.85) Log copies/106 cells |
e+: r = 0.843 p < 0.001 e−: r = 0.865 p < 0.001 |
e+: r = 0.710 p < 0.001 e−: r = 0.579 p = 0.002 |
| Caviglia GP [38] |
Italy | 2020 | 35 | 0/35 | D = 35 | No | 3.8 ± 1.8 Log U/mL |
3.13 ± 1.31 Log IU/mL |
3.11 ± 1.14 Log copies/105 cells |
r = 0.733 p < 0.001 |
r = 0.624 p < 0.001 |
| Dezanet LNC [39] |
France | 2020 | 31 M | 22/9 | A = 11 D = 1 E = 1 G = 4 n.a. = 14 |
NAs + ART (n = 22) |
5.5 (3.1–7.0) Log U/mL |
4.0 (3.2–4.5) Log IU/mL |
0.26 (0.0–2.89) copies/cell |
r = 0.65 p < 0.001 e+: r = 0.40 p = 0.07 e−: r = 0.22 p = 0.5 |
r = 0.68 p < 0.001 e+: r = 0.42 p = 0.10 e−: r = 0.68 p = 0.03 |
* Correlation between serum HBcrAg and intrahepatic HBV cccDNA values. ** Correlation between serum HBsAg and intrahepatic HBV cccDNA values. A Patients with HCC. B HBV cccDNA was measured in liver specimens from 22 out of 55 patients. C The analysis was performed of 305 samples from 138 patients: 138 pre-treatment samples, 124 after one year of receiving NAs and 43 after 6–12 years of therapy. D The original study reported the mean baseline HBcrAg, HBsAg, and HBV cccDNA values according to virologic response to Peg-IFN alone or combined to ETV (R vs. NR). E Patients with HCC. F HBV cccDNA was measured in liver specimens from 89 out of 160 patients. G The study cohort included 51 (40.5%) patients with HCC. H Three patients were excluded from correlation analysis. I Only patients with HBcrAg > 3 Log U/mL were included in the analysis. L Correlation analysis was performed only on the 32 patients with HBeAg-positive chronic hepatitis (the 4 patients with HBeAg-positive chronic infection were excluded). M 38 liver biopsies from 31 HIV–HBV coinfected patients. Abbreviations: adefovir (ADV), antiretroviral therapy (ART), cell equivalent (cEq), chronic infection (CI), chronic hepatitis (CH), correlation coefficient (r), covalently-closed-circular DNA (cccDNA), e antigen-positive (e+), e antigen-negative (e−), entecavir (ETV), hepatitis B core-related antigen (HBcrAg), hepatitis B e antigen (HBeAg), hepatitis B surface antigen (HBsAg), hepatitis B virus (HBV), hepatocellular carcinoma (HCC), human immunodeficiency virus (HIV), lamivudine (LAM), non-responder (NR), not available (n.a.), nucleos(t)ide analogues (NAs), number (n), responder (R).