. 2020 Oct 6;11(10):e00236. doi: 10.14309/ctg.0000000000000236

Table 1.

Baseline characteristics of the included studies (n = 13)

Study	Region	Design	Sample size		Sex		Age		HBeAg		Cirrhosis		ALT		HBV DNA		Treatment naive	FU time (mo)		Variables: PSM/adjustment	Exclusion criteria
Study	Region	Design	ETV	TDF	ETV	TDF	ETV	TDF	ETV	TDF	ETV	TDF	ETV	TDF	ETV	TDF	Treatment naive	ETV	TDF	Variables: PSM/adjustment	Exclusion criteria
Kim et al. (15)
PSM cohort Whole cohort	South Korea	Retrospective cohort study (1 tertiary referral hospital)	354 721	354 604	220 (62%) 471 (65%)	222 (63%) 363 (60%)	51 ± 12 52 ± 11	52 ± 11 50 ± 11	232 (66%) 430 (60%)	223 (64%) 376 (62%)	169 (48%) 346 (48%)	156 (44%) 267 (44%)	136 ± 159 143 ± 172	142 ± 229 137 ± 228	6.2 ± 1.4 6.4 ± 1.4	6.2 ± 1.5 6.0 ± 1.6	Yes Yes	n.a. 66 (36–88)	n.a. 33 (21–46)	1–15	(i) Decompensated cirrhosis, (ii) FU <1 yr, (iii) Cr >1.5 mg/dL, (iv) HBV DNA <2,000 IU/mL, and (v) death <6 mo or HCC <1 yr after NA
Choi et al. (12)
PSM cohort Whole cohort	South Korea	Retrospective cohort study (nationwide claims database of NHIS)	10,923 11,464	10,923 12,692	6,834 (62%) 11,464 (63%)	6,834 (63%) 12,692 (63%)	49 ± 10 49 ± 10	49 ± 10 49 ± 10	n.a. n.a.	n.a. n.a.	2,891 (27%)^a 2,991 (26%); D: 450 (4%)	2,919 (27%)^a 3,488 (28%); D: 414 (3%)	32 (21–54) 32 (21–54)	35 (24–57) 35 (24–58)	n.a. n.a.	n.a. n.a.	Yes Yes	51 (38–57) 51 (37–57)	37 (30–43) 37 (30–44)	1, 2, 3, 6, 14–20	(i) Age <30 or >80 yr; (ii) HCV, HDV, HIV; (iii) Previous organ transplant, HCC, or other cancer; and (iv) HCC, transplant, or death <6 mo after NA
Kim et al. (18)
PSM cohort Whole cohort	South Korea	Retrospective cohort study (4 academic teaching hospitals)	1,278 1,484	1,278 1,413	793 (62%) 889 (60%)	794 (62%) 913 (65%)	49 ± 11 48 ± 12	49 ± 12 49 ± 12	758 (50%) 758 (51%)	727 (50%) 694 (49%)	476 (32%) 499 (34%)	456 (32%) 411 (29%)	n.a. n.a.	n.a. n.a.	5.6 ± 2.1 5.7 ± 2.1	5.6 ± 2.1 5.4 ± 2.1	Yes Yes	n.a. 59	n.a.	1–4, 8, 9, 13–15	(i) Age <19 yr; (ii) decompensated cirrhosis; (iii) HCV, HDV; (iv) Previous organ transplant or HCC; (v) HCC, liver transplant, or death <6 mo of enrolment; (vi) and significant medical illness
Lee et al. (19)
PSM cohort Whole cohort	South Korea	Retrospective cohort study (1 tertiary referral hospital)	1,370 1,583	1,370 1,439	806 (59%) 926 (59%)	798 (58%) 841 (58%)	47 ± 12 47 ± 12	47 ± 11 47 ± 11	814 (59%) 974 (62%)	807 (59%) 823 (57%)	465 (34%) 567 (36%)	464 (34%) 483 (35%)	98 (53–200) 98 (53–201)	95 (50–196) 94 (51–194)	6.5 (5–8) 6.5 (5–8)	6.4 (5–8) 6.4 (5–8)	Yes Yes	n.a. 60	n.a. 36	1–15, 17, 18, 21–25	(i) HCV and HIV, (ii) HCC and transplant before or <6 mo after NA, (iii) other cancer, and (iv) decompensated cirrhosis
Yip et al. (14)
PSM cohort Whole cohort	Hong Kong, China	Retrospective cohort study (territory-wide healthcare database of public hospitals)	4,636 28,041	1,200 1,309	2,267 (49%) 18,094 (65%)	587 (49%) 591 (45%)	43 ± 13 53 ± 13	44 ± 13 43 ± 13	2,480 (54%) 8,317 (30%)	625 (52%) 721 (55%)	167 (4%) 3,822 (14%)	37 (3%) 38 (3%)	43 (25–108) 62 (33–137)	46 (26–107) 43 (25–103)	4.8 ± 2.8 5.3 ± 2.2	4.8 ± 2.7 4.9 ± 2.7	Yes Yes	35 (18–55) 44 (20–60)	34 (18–54) 34 (17–54)	1–6, 8–10, 12–15, 26–27	(i) HCV, HDV, HIV; (ii) autoimmune or metabolic liver disease; (iii) HCC and transplant before or <6 mo after NA; and (iv) FU <6 mo
Hsu et al. (16)
PSM cohort Whole cohort	Asia: 82% (Korea, Japan, China, Hong Kong, Taiwan); USA: 18%	Retrospective cohort study (19 centers from 6 countries or regions)	520 4,837	520 700	354 (68%) 3,328 (69%)	338 (65%) 456 (65%)	44 ± 0.5 51 ± 0.2	45 ± 0.6 46 ± 0.5	187 (36%) 1,537/4,653 (33%)	177 (34%) 208/617 (34%)	107 (21%) 1,344 (28%)^b	105 (20%) 131 (19%)^b	165 ± 16 200 ± 6	156 ± 14 147 ± 11	5.0 ± 0.1 5.5 ± 0.03	5.1 ± 0.1 5.0 ± 0.09	Yes Yes	60 (37–60) 44 (20–60)	39 (24–58) 34 (17–54)	1–6, 13, 14, 28, 29	(i) Age <18 yr; (ii) HCV, HDV, HIV; (iii) previous cancer, solid organ transplant, or immunosuppressant use; and (iv) HCC or death <1 yr of FU
Papatheodoridis et al. (20)
Whole cohort	Greece, Italy, Spain, Netherlands, and Turkey	PAGE-B cohort	772	1,163	538 (70%)	827 (71%)	52 ± 14	53 ± 13	110 (14%)	233 (20%)	166 (22%)	358 (31%)	54	36	5.4	3.3	^c	91	90	1–6, 13^d	(i) Age <16 yr; (ii) previous HCC, liver transplant; (iii) HCV, HDV, HIV; (iv) decompensated cirrhosis
Pol et al. (21)
Whole cohort	Europe, Africa, and Asia	ANRS CO22 Hepather cohort	1,143	1,515 (110 on both ETV & TDF)	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	45 (26–53)		1, 2, 12, 13, 15, 29–31	(i) HCV and HDV
Kim et al. (13)
Whole cohort	USA	Administrative claims dataset	4,060	6,145	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Yes	42	45	1, 2, 32, 33	(i) HCV, HDV, HIV and (ii) previous HCC or liver transplant or <6 mo after NA
Gordon et al. (22)
Whole cohort	USA (Asian and non-Asian)	Chronic Hepatitis Cohort Study	415	407	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	151 (18%)		n.a.	n.a.	n.a.	n.a.	^e	36		1–3, 22, 30	(i) HIV and (ii) previous liver transplant
Ha et al. (23)
PSM cohort	South Korea	Retrospective cohort study (1 tertiary referral hospital)	298 921	298 419	181 (60.7%) 558	181 (60.1%) 266	48 ± 16 48 ± 15	48 ± 14 45 ± 16	161 (54.0%) 488	174 (58.4%) 261	39 (13.1%) 259	39 (13.1%) 39	93 ± 148 94 ± 120	98 ± 118 103 ± 132	6.4 ± 2.8 6.4 ± 2.3	6.3 ± 2.5 6.7 ± 2.6	Yes Yes	n.a. n.a.	n.a. n.a.	1–9, 11–14, 17, 27, 34	(i) Age <18 yr; (ii) duration of therapy <1 yr; (iii) previous HCC, liver transplant, or death or <6 mo after NA; and (iv) pretreatment HBV DNA <2,000 IU/mL
Whole cohort	South Korea	Retrospective cohort study (1 tertiary referral hospital)	298 921	298 419	181 (60.7%) 558	181 (60.1%) 266	48 ± 16 48 ± 15	48 ± 14 45 ± 16	161 (54.0%) 488	174 (58.4%) 261	39 (13.1%) 259	39 (13.1%) 39	93 ± 148 94 ± 120	98 ± 118 103 ± 132	6.4 ± 2.8 6.4 ± 2.3	6.3 ± 2.5 6.7 ± 2.6	Yes Yes	n.a. n.a.	n.a. n.a.	1–9, 11–14, 17, 27, 34
Lee et al. (17)
Whole cohort	South Korea	Retrospective cohort study (1 tertiary referral hospital)	152	49	n.a.	n.a.	n.a.	n.a.	0	0	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Yes	60 (range: 24–132)		1–3, 5–6	(i) HBeAg positivity, (ii) HCV and HIV, (iii) concomitant chronic liver diseases, (iv) decompensated cirrhosis, and (v) previous HCC
Oh et al. (24)
PSM cohort	South Korea	Retrospective cohort study (9 academic hospitals)	516 753	516 807	319 (61.8%) 480 (63.7%)	325 (63.0%) 503 (62.3%)	49 ± 13 49 ± 11	49 ± 9 46 ± 11	314 (60.9%) 451 (61.4%)	311 (60.3%) 484 (60.0%)	238 (46.1%) 315 (41.8%)	224 (43.4%) 310 (38.4%)	n.a. n.a.	n.a. n.a.	6.4 (5.4–7.5) 6.5 (5.4–7.6)	6.4 (5.4–7.5) 6.6 (5.5–7.7)	Yes Yes	56 (52–64) 59 (53–57)	58 (47–65) 56.4 (46–65)	1–5, 8–15, 22, 29, 35, 36	(i) HCV and HIV, (ii) duration of therapy <1 yr, and (iii) previous HCC or death <1 yr after NA
Whole cohort	South Korea	Retrospective cohort study (9 academic hospitals)	516 753	516 807	319 (61.8%) 480 (63.7%)	325 (63.0%) 503 (62.3%)	49 ± 13 49 ± 11	49 ± 9 46 ± 11	314 (60.9%) 451 (61.4%)	311 (60.3%) 484 (60.0%)	238 (46.1%) 315 (41.8%)	224 (43.4%) 310 (38.4%)	n.a. n.a.	n.a. n.a.	6.4 (5.4–7.5) 6.5 (5.4–7.6)	6.4 (5.4–7.5) 6.6 (5.5–7.7)	Yes Yes	56 (52–64) 59 (53–57)	58 (47–65) 56.4 (46–65)	1–5, 8–15, 22, 29, 35, 36

Continue variables expressed as mean (±1 SD) or median (interquartile range).

AFP, alpha fetoprotein; ALT, alanine aminotransferase; APRI, AST/platelet ratio index; AST, aspartate aminotransferase; BMI, body mass index; CPS, Child-Pugh score; Cr, creatinine; CTP, Child-Turoctte-Pugh; DM, diabetes mellitus; ETV, entecavir; FIB-4, fibrosis-4 index; FU, follow-up; GGT, gamma-glutamyl transferase; HBeAg, hepatitis B e antigen; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HDV, hepatitis D virus; INR, international normalized ratio; MELD, model for end-stage liver disease; n.a., not available; NA, nucleos(t)ide analog; Peg-IFN, pegylated-interferon; PS, propensity score; PSM, propensity score matched; PT, prothrombin time; RRT, renal replacement therapy; SES, socioeconomic status; TDF, tenofovir.

Decompensated cirrhosis: ETV group 421 (4%), TDF group 388 (4%).

CPS B/C: ETV group 136 (3%), TDF group 29 (4%).

Both treatment naive and experienced.

Not adjusted for HBeAg, previous treatment use, ALT, HBV DNA despite significant difference between ETV and TDF groups.

One hundred sixty-four (20%): only treatment-naive patients were included for analysis in current meta-analysis.

1, age; 2, sex; 3, cirrhosis; 4, HBeAg; 5, HBV DNA; 6, ALT; 7, AST; 8, albumin; 9, bilirubin; 10, creatinine; 11, AFP; 12, INR or PT; 13, platelet; 14, DM; 15, hypertension; 16, smoking; 17, drinking; 18, BMI; 19, SES; 20, healthcare level; 21, APRI; 22, FIB-4; 23, CPS; 24, varix; 25, GGT; 26, RRT; 27, calendar year of treatment initiation; 28, country; 29, hepatic decompensation; 30, ethnicity; 31, fibrosis stage; 32, health conditions; 33, weighting based on treatment PS; 34, HBsAg titer; 35, CTP; 36, MELD.