INTRODUCTION

METHODS
Protocol and registration
Data sources and search strategy
Study inclusion criteria
Study selection and data extraction
Quality and risk of bias assessment
Outcome measures
Statistical analysis

RESULTS
Study selection and characteristics
![]() | Figure 1PRISMA flow diagram showing the literature search strategy. PRISMA, Preferred Reporting Items for Systematic review and Meta-Analysis; RCT, randomized controlled trial; PSM, propensity score-matched. |
Table 1
Study (year) | Country | Study design | Treatment | Sample size | Age (yr) | Male (%) | Cirrhosis (%) | HBeAg positivity (%) | HBV DNA (log10 IU/mL) | ALT (U/L) |
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Jung et al. (2022) [27] | South Korea | PSM | BSV | 154 | 48.5 | 97 (63.0) | 59 (38.3) | 85 (55.2) | 5.8 | 78.0 |
TAF | 154 | 49.2 | 90 (58.4) | 65 (42.2) | 75 (48.7) | 5.6 | 59.0 | |||
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Lim et al. (2022) [28] | South Korea | PSM | TAF | 495 | 48.7 | 267 (53.9) | 157 (31.7) | 242 (48.9) | 6.2 | 158.4 |
TDF | 495 | 47.6 | 273 (55.2) | 158 (31.9) | 253 (51.5) | 6.3 | 167.9 | |||
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Shin et al. (2021) [33] | South Korea | PSM | ETV | 589 | 50.0 | 365 (62.0) | 276 (46.9) | 365 (62.0) | 6.1 | 84.0 |
TDF | 589 | 50.0 | 358 (60.8) | 282 (47.9) | 354 (60.1) | 6.2 | 71.0 | |||
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Yang et al. (2021) [29] | China | PSM | ETV | 124 | 34.6 | 82 (66.1) | 24 (19.4) | 105 (84.7) | 7.2 | 155.0 |
TDF | 124 | 32.7 | 72 (58.1) | 18 (14.5) | 108 (87.1) | 7.2 | 128.0 | |||
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Lee et al. (2020) [30] | South Korea | PSM | ETV | 1370 | 47.0 | 806 (58.8) | 465 (33.9) | 814 (59.4) | 6.5 | 98.0 |
TDF | 1370 | 46.9 | 798 (58.3) | 464 (33.9) | 807 (58.9) | 6.4 | 94.5 | |||
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Yip et al. (2020) [31] | China | PSM | ETV | 4636 | 42.9 | 2267 (48.9) | 167 (3.6) | 2480 (53.5) | 4.8 | 43.0 |
TDF | 1200 | 44.4 | 587 (48.9) | 37 (3.1) | 625 (52.1) | 4.8 | 45.5 | |||
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Ahn et al. (2019) [8] | South Korea | RCT | BSV | 94 | 47.0a) | 60 (63.8) | 24 (25.5) | 56 (59.6) | 6.2a) | 76.5a) |
TDF | 93 | 43.0a) | 59 (63.4) | 17 (18.3) | 55 (59.1) | 6.8a) | 80.0a) | |||
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Cai et al. (2019) [21] | China | RCT | ETV | 158 | 31.0 | 121 (76.6) | 0 (0.0) | 158 (100.0) | 7.7 | NA |
TDF | 157 | 30.8 | 119 (75.8) | 0 (0.0) | 157 (100.0) | 7.6 | NA | |||
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Zhao et al. (2019) [22] | China | RCT | ETV | 45 | 68.2 | NA | NA | 45 (100.0) | 6.0 | 189.1 |
TDF | 48 | 66.4 | NA | NA | 48 (100.0) | 5.8 | 200.1 | |||
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Choi et al. (2019) [32] | South Korea | PSM | ETV | 869 | 48.8 | 519 (59.7) | 511 (58.8) | 479 (55.1) | 6.5 | 85a) |
TDF | 869 | 48.8 | 540 (62.1) | 505 (58.1) | 481 (55.4) | 6.5 | 83a) | |||
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Koike et al. (2018) [23] | Japan | RCT | ETV | 56 | 46.1 | 40 (71.4) | NA | 28 (50.0) | 7.2 | 76.7 |
TDF | 109 | 45.4 | 68 (62.4) | NA | 51 (46.8) | 7.0 | 90.4 | |||
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Sriprayoon et al. (2017) [24] | Thailand | RCT | ETV | 200 | 41.6 | 121 (60.5) | 31 (15.5) | 95 (47.5) | 6.8 | 68.1 |
TDF | 200 | 41.2 | 113 (56.5) | 29 (14.5) | 92 (46.0) | 6.7 | 76.8 | |||
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Zhang et al. (2017) [25] | China | RCT | ETV | 98 | 36.1 | 58 (59.2) | NA | 56 (57.1) | 6.7 | 130.5 |
TDF | 98 | 35.9 | 60 (61.2) | NA | 60 (61.2) | 6.6 | 135.3 | |||
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Park et al. (2017) [9] | South Korea | PSM | ETV | 105 | 47.0 | 64 (61.0) | 43 (41.0) | 58 (55.2) | 6.6 | 179.5 |
TDF | 105 | 45.5 | 67 (63.8) | 41 (39.0) | 63 (60.0) | 6.7 | 232.3 | |||
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Wu et al. (2017) [10] | Taiwan | PSM | ETV | 212 | 46.3 | 162 (76.4) | 57 (26.9) | 100 (47.2) | 7.3 | 346.0 |
TDF | 106 | 47.1 | 74 (70.0) | 29 (27.4) | 50 (47.1) | 7.4 | 303.0 | |||
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Lai et al. (2014) [26] | South Korea | RCT | BSV | 39 | 40.0 | 32 (82.1) | 0 (0.0) | 21 (53.8) | 6.8 | 140.2 |
ETV | 39 | 41.3 | 31 (79.5) | 0 (0.0) | 22 (56.4) | 7.0 | 141.9 |
HBeAg, hepatitis B e antigen; HBV, hepatitis B virus; ALT, alanine aminotransferase; PSM, propensity score-matched; BSV, besifovir dipivoxil maleate; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate; ETV, entecavir; RCT, randomized controlled trial; NA, data not provided or unavailable.
Publication bias and quality assessment of individual studies
Inconsistency test
VR: HBV DNA suppression after 48 and 96 weeks of NA treatment
![]() | Figure 2Network plot comparing study outcomes for the four nucleos(t)ide analogues. Line widths and circle sizes are proportional to the number of studies included. (A) 48-week virologic response. (B) 96-week virologic response. (C) 48-week biochemical response. (D) 48-week serologic response. ETV, entecavir; BSV, besifovir dipivoxil maleate; TDF, tenofovir disoproxil fumarate; TAF, tenofovir alafenamide. |
![]() | Figure 3Forest plot of network meta-analyses demonstrating study outcomes in comparison with those of four nucleos(t)ide analogues. (A) 48-week virologic response. (B) 96-week virologic response. (C) 48-week biochemical response. (D) 48-week serologic response. TDF, tenofovir disoproxil fumarate; ETV, entecavir; TAF, tenofovir alafenamide; BSV, besifovir dipivoxil maleate; OR, odds ratio; CI, confidence interval. |
Table 2
BR: ALT normalization after 48 weeks of NA treatment
SR: HBeAg seroclearance after 48 weeks of NA treatment
VB after 48 weeks of NA treatment
HBsAg loss after 48 weeks of NA treatment
Rankogram showing efficacy comparisons by NA
![]() | Figure 4Rankograms for all outcome measures generated by network meta-analyses. Mean ranks were generated after 10,000 repeated simulations. (A) 48-week virologic response. (B) 96-week virologic response. (C) 48-week biochemical response. (D) 48-week serologic response. NA, nucleos(t)ide analogue; BSV, besifovir dipivoxil maleate; ETV, entecavir; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate. |
Sensitivity analyses
Subgroup analyses based on the presence or absence of HBeAg

DISCUSSION
