Clin Mol Hepatol > Volume 27(3); 2021 > Article |
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Study | Drug, sample size | Age (years) | HBeAg (+) | HBV DNA (log10 IU/mL) | Cirrhosis | NUC-naïve | Follow-up duration (months) | HCC, n (/100 person-year) | Main findings | ||
---|---|---|---|---|---|---|---|---|---|---|---|
Hospital cohort study (from Asian countries) | |||||||||||
Kim et al. [11] (2019/multicenter/Korea) | |||||||||||
Whole cohort | ETV: 1,484 | 48.2 | 758 (51.1) | 5.7±2.1 | 499 (33.6) | 1,484 (100.0) | 59.2 | 138 (1.92) | aHR: 0.98 (95% CI, 0.75–1.27) | ||
TDF: 1,413 | 48.8 | 694 (49.1) | 5.4±2.1 | 411 (29.1) | 1,413 (100.0) | 59.2 | 102 (1.69) | ||||
PSM cohort | ETV: 1,278 | 48.6 | 640 (50.1) | 5.6±2.1 | 394 (30.8) | 1,278 (100.0) | NA | NA (1.74) | aHR: 1.02 (95% CI, 0.77–1.35) | ||
TDF: 1,278 | 48.2 | 640 (50.1) | 5.6±2.1 | 400 (31.3) | 1,278 (100.0) | NA | NA (1.58) | ||||
Lee et al. [12] (2020/multicenter/Korea) | |||||||||||
Whole cohort | ETV: 1,583 | 46.7 | 974 (61.5) | 6.5 (5.3–7.7) | 60.0 | 1,583 (100.0) | 60.0 | 84 (1.09) | aHR: 0.97 (95% CI, 0.68–1.40) | ||
TDF: 1,439 | 47.3 | 823 (57.2) | 6.4 (5.3–7.5) | 36.4 | 1,439 (100.0) | 36.4 | 50 (1.12) | ||||
PSM cohort | ETV: 1,370 | 47.0 | 814 (59.4) | 6.5 (5.3–7.1) | 465 (33.9) | 1370 (100.0) | 51.5 | 64 (1.06) | aHR: 1.08 (95% CI, 0.52–2.24) | ||
TDF: 1,370 | 46.9 | 807 (58.9) | 6.4 (5.3–7.5) | 464 (33.9) | 1370 (100.0) | 36.6 | 47 (0.96) | ||||
Chang et al. [13] (2021/multicenter/Taiwan) | |||||||||||
Whole cohort | ETV: 5,348 | 51.0 | 849 (16.0) | 3.5±2.3 | 1,590 (30.0) | 4,888 (91.4) | 39.6 | 375 (2.13) | aHR: 0.82 (95% CI, 0.66–1.02) | ||
TDF: 1,900 | 51.0 | 544 (29.0) | 3.2±2.3 | 590 (31.0) | 1,460 (76.8) | 40.1 | 100 (1.58) | ||||
PSM cohort | ETV: 3,304 | 52.0 | 586 (18.0) | 3.4±2.3 | 930 (28.0) | 3,036 (91.9) | 40.1 | NA (2.03) | aHR: 0.83 (95% CI, 0.65–1.06) | ||
TDF: 1,652 | 52.0 | 435 (26.0) | 3.1±2.3 | 509 (31.0) | 1,269 (76.8) | 41.0 | NA (1.67) | ||||
Ha et al. [14] (2020/single center/Korea) | |||||||||||
Whole cohort | ETV: 921 | 48 | 488 (53.0) | 6.4±2.3 | 259 (28.0) | 921 (100.0) | 54.2 | 82 (NA) | aHR: 1.84 (95% CI, 0.90–3.79) | ||
TDF: 419 | 45 | 261 (62.0) | 6.7±2.6 | 39 (9.3) | 419 (100.0) | 54.2 | 24 (NA) | aHR by IPTW: 1.30 (95% CI, 0.81–2.10) | |||
PSM cohort | ETV: 298 | 48 | 161 (54.0) | 6.4±2.8 | 39 (9.0) | 298 (100.0) | NA | NA | aHR: 2.06 (95% CI, 0.98–4.33) | ||
TDF: 298 | 48 | 174 (58.0) | 6.3±2.5 | 39 (9.0) | 298 (100.0) | NA | NA | ||||
Shin et al. [15] (2021/single center/Korea) | |||||||||||
Whole cohort | ETV: 894 | 52.0 | 537 (60.1) | 6.5 (5.3–7.8) | 440 (49.2) | 894 (100.0) | 82.8 | 74 (NA) | aHR: 0.83 (95% CI, 0.52–1.31) | ||
TDF: 900 | 51.0 | 565 (62.8) | 5.2 (3.3–7.0) | 375 (41.7) | 900 (100.0) | 45.6 | 31 (NA) | aHR by IPTW: 0.69 (95% CI, 0.43–1.11) | |||
PSM cohort | ETV: 589 | 50.0 | 365 (62.0) | 6.1 (5.0–7.4) | 276 (46.9) | 589 (100.0) | 58.3 | 40 (1.40) | aHR: 0.77 (95% CI, 0.46–1.29) | ||
TDF: 589 | 50.0 | 354 (60.1) | 6.2 (5.0–7.6) | 282 (47.9) | 589 (100.0) | 43.0 | 23 (1.09) | ||||
Hsu et al. [16] (2020/multicenter/international mostly from Asia) | |||||||||||
Whole cohort | ETV: 4,837 | 50.8 | 1,537 (330) | 5.5±0.0 | 1,344 (27.8) | 4,837 (100.0) | 60.0 | 285 (1.45) | aHR: 0.81 (95% CI, 0.42–1.56) | ||
TDF: 700 | 45.7 | 208 (33.7) | 5.0±0.1 | 131 (18.7) | 700 (100.0) | 38.7 | 13 (0.64) | ||||
PSM cohort | ETV: 520 | 44.1 | 161 (54.0) | 5.0±0.1 | 107 (20.6) | 520 (100.0) | 60.0 | 19 (1.02) | aHR: 0.89 (95% CI, 0.41–1.92) | ||
TDF: 520 | 44.9 | 174 (58.0) | 5.1±0.1 | 105 (20.1) | 520 (100.0) | 38.9 | 11 (0.71) | ||||
Oh et al. [17] (2020/multicenter/Korea) | |||||||||||
Whole cohort | ETV: 753 | 48.7 | 451 (61.4) | 6.5 (5.4–7.6) | 315 (41.8) | 753 (100.0) | 56.4 | 34 (1.0) | uHR: 1.26 (95% CI, 0.81–1.97) | ||
TDF: 807 | 46.3 | 484 (60.0) | 6.6 (5.5–7.7) | 310 (38.4) | 807 (100.0) | 54.0 | 45 (1.1) | ||||
PSM cohort | ETV: 516 | 49.2 | 314 (60.9) | 6.4 (5.4–7.5) | 238 (46.1) | 516 (100.0) | 58.8 | 29 | aHR: 1.30 (95% CI, 0.80–2.02) | ||
TDF: 516 | 49.0 | 311 (60.3) | 6.4 (5.4–7.5) | 224 (43.4) | 516 (100.0) | 56.4 | 37 | ||||
Yu et al. [18] (2018/single center/Korea) | ETV: 406 | 53.0 | 212 (52.2) | 6.1 (1.1-9.3) | 148 (36.5) | 406 (100.0) | 69.9 | 31 (1.33) | uHR: 1.39 (95% CI, 0.56–3.45) | ||
TDF: 176 | 49.0 | 104 (59.1) | 6.9 (1.2-8.8) | 77 (43.8) | 176 (100.0) | 33.6 | 7 (1.25) | ||||
Lee et al. [19] (2021/Multicenter/Korea) | ETV: 405 | 57 | 111 (27.4) | 2.4±1.8 | 183 (45.2) | 206 (50.1) | 47.4 | 100 (2.28) | aHR: 0.93 (95% CI, 0.70–1.23) | ||
TDF: 321 | 55 | 124 (38.6) | 3.3±2.1 | 129 (40.2) | 210 (65.4) | 44.5 | 127 (1.79) | ||||
Hospital cohort study (from Western countries) | |||||||||||
Papatheodoridis et al. [20] (2020/multicenter/Greece, Italy, Netherlands, Spain, Turkey) | ETV: 772 | 52 | 110 (14.0) | 5.4 | 166 (21.5) | 607 (78.6) | 91.2 | 50 (0.96) | aHR: 1.07 (95% CI, 0.64–1.81) | ||
TDF: 1,163 | 53 | 233 (20.0) | 3.3 | 358 (30.8) | 521 (44.8) | 90.0 | 93 (1.01) | ||||
Pol et al. [21] (2021/multicenter/France) | ETV: 814 | 49.2 | 106 (13.0) | 1.3 (1.1–1.3) | 69 (9.0) | 519 (64.0) | 50.4 | 9 (0.16) | aHR: 1.51 (95% CI, 0.58–3.92) | ||
TDF: 986 | 44.8 | 186 (19.0) | 1.3 (1.2–1.3) | 90 (9.0) | 476 (48.0) | 50.4 | 12 (0.18) | aHR by IPTW: 1.24 (95% CI, 0.49–3.13) | |||
Administrative study (from Asian countries) | |||||||||||
Choi and Seo [22] (2021/multicenter/Korea) | |||||||||||
Whole cohort | ETV: 21,486 | 48.4 | 7,692 (35.8) | 21,486 (100) | 39.8 | ||||||
TDF: 54,799 | 46.1 | 18,561 (33.9) | 54,799 (100) | 42.8 | |||||||
PSM cohort | ETV: 18,491 | 47.1 | 6,230 (33.7) | 18,491 (100) | 41.2 | 912 (1.46) | aHR: 0.93 (95% CI, 0.86–1.01) | ||||
TDF: 36,982 | 47.0 | 12,460 (33.7) | 36,982 (100) | 41.1 | 1,708 (1.36) | ||||||
Administrative study (from Western countries) | |||||||||||
Su et al. [23] (2021/multicenter/USA) | ETV: 2,193 | 56.5 | 664 (30.3) | 4.3 (2.1–6.9) | 453 (20.7) | 1,305 (59.5) | NA | 167 (1.36) | aHR: 1.00 (95% CI, 0.76–1.32) | ||
TDF: 1,094 | 55.4 | 250 (22.9) | 3.7 (1.7–6.5) | 228 (20.8) | 701 (64.1) | NA | 85 (1.64) | aHR by PS: 1.00 (95% CI, 0.76–1.32) |
Values are presented as mean±standard deviation, number (%), or number (interquartile ranges) unless otherwise indicated.
HCC, hepatocellular carcinoma; TDF, tenofovir disoproxil fumarate; ETV, entecavir; HBeAg, hepatitis B e antigen; HBV, hepatitis B virus; NUC, nucleos(t)ide analogue; aHR, adjusted hazard ratio; CI, confidence interval; PSM, propensity score matched; NA, not applicable; IPTW, inverse probability of treatment weighting; uHR, unadjusted hazard ratio; PS, propensity score.
Study | Drug, sample size | Age (years) | HBeAg (+) | HBV DNA (log10 IU/mL) | Cirrhosis | NUC-naïve | Follow-up duration (months) | HCC, n (/100 person-year) | Main findings | ||
---|---|---|---|---|---|---|---|---|---|---|---|
Hospital cohort study (from Asian countries) | |||||||||||
Chen et al. [28] (2020/multicenter/Taiwan) | |||||||||||
Whole cohort | ETV: 993 | 55.4 | 209 (21.0) | 5.4±1.5 | 993 (100.0) | 875 (88.1) | 65.8 | 196 (3.6) | aHR: 0.67 (95% CI, 0.48–0.93) | ||
TDF: 567 | 54.5 | 130 (22.9) | 5.4±1.4 | 567 (100.0) | 478 (84.3) | 47.7 | 48 (2.2) | ||||
PSM cohort | ETV: 545 | 54.3 | 129 (23.6) | 5.4±1.4 | 545 (100.0) | 468 (85.9) | NA | NA | aHR: 0.66 (95% CI, 0.46–0.95) | ||
TDF: 545 | 54.5 | 125 (22.9) | 5.4±1.4 | 545 (100.0) | 462 (84.8) | NA | NA | ||||
Ha et al. [24] (2020/single center/Korea) | |||||||||||
Whole cohort | ETV: 180 | 45.4 | 118 (67.4) | 7.7 | 67 (37.2) | 180 (100.0) | 64.0 | 18 (2.19) | aHR: 0.31 (95% CI, 0.12–0.79) | ||
TDF: 224 | 44.5 | 128 (57.1) | 7.4 | 78 (34.8) | 224 (100.0) | 49.1 | 6 (0.71) | ||||
PSM cohort | ETV: 168 | 45.4 | 111 (66.1) | 7.8 | 58 (34.5) | 168 (100.0) | 64.8 | aHR: 0.27 (95% CI, 0.08–0.98) | |||
TDF: 168 | 45.0 | 109 (64.9) | 7.7 | 56 (33.3) | 168 (100.0) | 49.6 | |||||
Choi et al. [10] (2019/single center/Korea) | |||||||||||
Whole cohort | ETV: 1,560 | 49.2 | 853 (54.7) | 6.7±1.6 | 935 (59.9) | 1,560 (100.0) | 48.0 | 115 (2.26) | aHR: 0.66 (95% CI, 0.46–0.96) | ||
TDF: 1,141 | 48.1 | 641 (56.2) | 6.4±.5 | 653 (57.2) | 1,141 (100.0) | 32.0 | 39 (1.31) | ||||
PSM cohort | ETV: 869 | 48.8 | 479 (55.1) | 6.5±1.5 | 519 (59.7) | 869 (100.0) | 48.0 | 61 (2.17) | aHR: 0.68 (95% CI, 0.46–0.99) | ||
TDF: 869 | 48.8 | 481 (55.4) | 6.5±1.5 | 505 (58.1) | 869 (100.0) | 32.0 | 31 (1.37) | ||||
Administrative study (from Asian countries) | |||||||||||
Choi et al. [10] (2019/multicenter/Korea) | |||||||||||
Whole cohort | ETV: 11,464 | 49.3 | NA | NA | 2,991 (26.1) | 11,464 (100.0) | 51.0 | 590 (1.19) | aHR: 0.68 (95% CI, 0.59–0.77) | ||
TDF: 12,692 | 48.6 | 3,488 (27.5) | 12,692 (100.0) | 36.0 | 394 (0.89) | ||||||
PSM cohort | ETV: 10,923 | 49.1 | NA | NA | 2,891 (26.5) | 10,923 (100.0) | 51.0 | 567 (1.20) | aHR: 0.68 (95% CI, 0.60–0.78) | ||
TDF: 10,923 | 49.0 | 2,919 (26.7) | 10,923 (100.0) | 36.0 | 0.92 (0.92) | ||||||
Yip et al. [29] (2020/Hong Kong) | |||||||||||
Whole cohort | ETV: 28,041 | 53.4 | 14,665 (52.3) | 4.8±2.7 | 1,290 (4.6) | 28,041 (100.0) | 33.6 | 1,386 (0.59) | aHR: 0.33 (95% CI, 0.16–0.67) | ||
TDF: 1,309 | 43.2 | 721 (55.1) | 4.9±2.7 | 38 (2.9) | 1,309 (100.0) | 33.6 | 8 (0.21) | ||||
PSM cohort | ETV: 4,636 | 42.9 | 2,480 (53.5) | 4.8 ± 2.8 | 167 (3.6) | 4,636 (100.0) | 33.6 | aHR: 0.39 (95% CI, 0.18–0.84) | |||
TDF: 1,200 | 44.4 | 625 (52.1) | 4.8 ± 2.7 | 37 (3.1) | 1,200 (100.0) | 34.8 | |||||
Administrative study (from Western countries) | |||||||||||
Kim et al. [30] (2019/multicenter/USA) | ETV: 4,060 | 48.0 | NA | NA | NA | 4,060 (100) | 16.9 | 49 (0.61) | aHR: 0.56 (95% CI, 0.37–0.86) | ||
TDF: 6,145 | 44.0 | 6,145 (100) | 18.1 | 41 (0.32) |
Values are presented as mean±standard deviation or number (%) unless otherwise indicated.
HCC, hepatocellular carcinoma; TDF, tenofovir disoproxil fumarate; ETV, entecavir; HBeAg, hepatitis B e antigen; HBV, hepatitis B virus; NUC, nucleos(t)ide analogue; aHR, adjusted hazard ratio; CI, confidence interval; PSM, propensity score matched; NA, not applicable.
Seung Up Kim
https://orcid.org/0000-0002-9658-8050
Young-Suk Lim
https://orcid.org/0000-0002-1544-577X
Recent advances in the management of hepatocellular carcinoma2024 January;30(1)