Literature search
The study selection process is summarized in Figure 1.We identified 6102 relevant studies though database searches,After the initial screening and eligibility assessment phase,1972 redundant publications were excluded and, after referring to the titles and abstracts,a further 41 studies that not fulfilling the inclusion criteria were rejected. The remaining 4 studies without sufficient data were rejected, Finally,7 studies were enrolled in this meta-analysis.Five of the articles were retrospective cohort analyse[13-17] and two was an RCTs[18, 19].A total of 1088 patients, 522 of whom were treated with LdT and 566 with ETV were included in this meta-analysis.The LdT dose used in the studies was 600 mg/day and that of ETV was 0.5 mg/day.
Study characteristics
Table 1 summarizes the basic characteristics of the included studies and patients .Three of the included studies were from mainland, China[13, 16, 19].{Liu, 2019 #27;Yan, 2012 #37;Qi, 2015 #47}two studies from Taiwan, China[14, 15], one studies from Korea[17] and one study from worldwide[18]. The included studies were published between 2010 and 2020.The sample size for each study ranged from 41 to 503.The mean age of the patients was 46.96 years (ranged from 38.3 to 55.2years old). The duration of follow-up ranged from 1 year to 5 year.Male patients accounted for approximately 70.2% (ranged from 66.7% to 77%) of all patients.Two publications[14, 15] reported by the same first author were confirmed not to overlap due to the use of different study periods,so they were included in the study.
Table 1 Characteristics of included studies
|
Study Design
|
Year
|
Region
|
Study type
|
Interventions
|
Sample size
|
Men sex (%)
|
Agea (years)
|
Follow-up period
|
Liu et al.
|
2020
|
China
|
Cohort
|
LdT/ETV
|
LdT: 21 ETV:20
|
66.7%
|
38.25
|
1.5 years
|
Tsai et al.
|
2016
|
Taiwan
|
Cohort
|
LdT/ETV/TDF
|
LdT:42 ETV:62 TDF:37
|
77%
|
55.2
|
2 years
|
Tsai et al.
|
2015
|
Taiwan
|
Cohort
|
LdT/ETV/TDF
|
LdT:79 ETV:119 TDF:75
|
71.7%
|
52.9
|
5 years
|
X. Qi et al.
|
2015
|
China
|
Cohort
|
LAM/ADV/LdT/ETV
|
LAM:11 ADV:17 LdT:8 ETV: 20 Untreated:6
|
73%
|
42
|
2 years
|
Lee et al.
|
2015
|
Korea
|
Cohort
|
LdT/ETV
|
LdT: 61 ETV: 310
|
67.0%
|
53.8
|
1.5 years
|
Gane et al.
|
2013
|
Worldwide
|
RCT
|
LdT/LAM
|
LdT: 261 LAM: 242
|
NA
|
NA
|
2 years
|
Han et al.
|
2012
|
China
|
RCT
|
LdT/ETV/ADV
|
LdT: 50 ETV:35 ADV:30
|
69%
|
39.6
|
1 year
|
ADV adefovir, ETV entecavir, LdT telbivudine, TDF tenofovir, RCT randomized controlled trial,N/A not applicable
Changes in eGFR with LdT therapy
Six included studies,involving 514 patients, reported the change in eGFR after 1 year of LdT treatment (Fig. 2). The results showed that the eGFR was improved by 7.02 mL/min/1.73 m2 with LdT after 1 year of treatment.There was statistical heterogeneity was observed among these studies(I2 = 85%,P < 0.00001) with a random-effects model.The result indicated a statistically significant change in the eGFR significant (RR = 7.02, 95%CI: 2.69–11.35, Z = 3.17; P =0.001).
Changes in eGFR with ETV therapy
Five included studies, including 546 patients,investigated the change in eGFR after 12 months of treatment with ETV (Fig. 3).The results showed that the eGFR was slightly increased after ETV treatment compared with baseline (1.72 mL/min/1.73 m2), and there was no significant heterogeneity among these studies (I2 = 43%,P = 0.14) with a fixed-effect model.The overall test result indicated that the eGFR was slightly increased after 12 months of treatment with ETV (RR = 1.72, 95%CI: 0.09–3.35,Z = 2.07; P = 0.04).
Renal safety comparison between LdT therapy group and ETV therapy group
There is no significant differences in baseline demographic data (age, gender) and eGFR level between the study groups.Two studies comprising 412 patients reported the change in eGFR after 6 months of treatment,as shown in Figure 4a,The eGFR was significantly higher in the LdT therapy group than in the ETV group after 6 months(RR = 4.63, 95%CI: 0.73–8.54,Z = 2.33; P = 0.02).and there was no significant heterogeneity among these studies (I2 = 0%,P = 0.95) with a fixed-effect model. Five studies comprising 788 patients reported the change in eGFR after 1 year of treatment,as shown in Figure 4b,The eGFR was significantly higher in the LdT therapy group than in the ETV group after 1 year(RR = 3.35, 95%CI: 1.18–5.52,Z = 3.02; P = 0.002).and there was no significant heterogeneity among these studies (I2 = 0%,P = 0.82) with a fixed-effect model.Three studies comprising 284 patients reported the change in eGFR after 2 year of treatment,as shown in Figure 4c,The eGFR was significantly higher in the LdT therapy group than in the ETV group after 2 year(RR = 11.00, 95%CI: 4.84–17.15,Z = 3.50; P = 0.0005) .and there was significant heterogeneity among these studies (I2 = 53%,P = 0.12) with a random-effects model. The changes trends in eGFR during treatment in the LdT and ETV groups are shown in Fig.5.
Risk of bias
All trials were evaluated by the Cochrane Collaboration’s risk–of-bias tool.The risk of bias assessment conducted for each study included is presented in Fig. 6.