Efficacy and safety of tenofovir disoproxil fumarate versus entecavir in the treatment of chronic liver failure due to hepatitis B: a systematic review and meta-analysis BMC Gastroenterology

Basic characteristics and risk of bias assessment of included studies

As a result, 95 articles were retrieved, and a total of 5 studies (19, 20, 21, 22, 23) with 272 patients were finally included. The article screening process is shown in Figure 1. The five studies were divided into four prospective cohort studies (19, 20, 22, 23) and one retrospective cohort study (21). The details of the five articles are shown in Table 1. A risk of bias analysis was performed on the included studies. Based on the quality analysis, the risk of bias of all studies was acceptable, as shown in Table 2.

survival rate

Three included studies (19, 20, 22) reported the 4-week survival rate of patients and found that TDF did not significantly improve 4-week survival rate compared with the ETV group (RR = 1.17, 95% CI: 0.90) –1.51 , p = 0.24). Five studies (19, 20, 21, 22, 23) provided data on 12-week survival, and combined analysis found no significant difference between the two groups (RR = 1.00, 95% CI: 0.88–1.13, p = 0.94). Two studies comparing 48-week survival in HBV-ACLF (20, 22) showed no significant difference between the two groups (RR = 0.96, 95% CI: 0.58–1.57, p = 0.86) (Fig. 2).

Effect of antiviral treatment on HBV-DNA

Three studies (19,20,21) compared HBV-DNA levels between the two groups at 2 weeks and found no significant difference in HBV-DNA levels between TDF and ETV (SMD = 0.07, 95% CI: -0.55 –0.68, p = 0.83) (Fig. 3A). Three studies (21,22,23) reported unmonitored HBV-DNA rates at 12 weeks and demonstrated that TDF was not effective in improving patients’ HBV-DNA clearance compared with ETV (RR = 1.89, 95% CI: 0.57–6.29, p = 0.30) (Figure 3B).

Serum surface antigen conversion

In the study by Wan et al. (21) Two and four HBeAg+ patients in the ETV group and TDF group survived for 3 months. Among these patients, 4 patients in the ETV group (0%; 0/2) and the TDF group (100%; 4/4) did not lose HBeAg (p = 0.067). None had HBeAg seroconversion at 3 months. Zhang et al. (22) reported no surface antigen loss in either group at week 48. There was 1 case of HBeAg seroconversion in each group, and the conversion times in the TDF group and ETV group were 12 weeks and 48 weeks respectively.

biochemical reaction

Regarding changes in liver function, three studies (19, 20, 22) examined changes in alanine aminotransferase (ALT) and total bilirubin (TBiL) in the TDF and ETV groups at 4 weeks. Results showed improvement in ALT and TBiL compared with baseline levels, but no significant difference between the two groups (ALT: SMD = 0.65, 95% CI: − 0.04 − 1.34, p

= 0.06; TBiL: SMD = − 0.01, 95% CI: − 0.35 − 0.33, p= 0.93). Only one study (22) reported ALT and TBiL at weeks 12 and 48 and found that TDF did not improve ALT and TBiL levels in patients with ACLF compared with ETV (p> 0.05). See Figure 4 for more details.

CTP score and MELD score

One study (21) and three studies (20,21,22) reported CTP and MELD scores at 4 weeks, respectively. Both CTP and MELD scores belonged to two independent groups (p > 0.05 between baseline, comparable). After 4 weeks of treatment, ETV failed to improve CTP scores or MELD scores, while TDF improved CTP and MELD scores (CTP: SMD = – 0.62, 95% CI: − 1.11 − − 0.13, p

= 0.01; MELD: SMD = − 0.72, 95% CI: -1.05 − − 0.39, p< 0.0001). Two studies (21, 23) and three studies (20, 21, 22) respectively mentioned CTP and MELD scores at 12 weeks, and TDF did not improve either score in patients with ACLF compared with ETV (CTP: SMD = -0.75, 95% CI: -2.81–1.30, p= 0.47; MELD: SMD = -1.10, 95% CI: − 2.29 − 0.08, p= 0.07). The forest diagram is shown in Figure 5. Only one study (22) reported MELD scores at 24 weeks, with no significant differences between the two groups (p> 0.05).

Safety of TDF and ETV in HBV-ACLF

Two studies by Zhang et al. and Li et al. (20, 22) provided changes in estimated glomerular filtration rate (eGFR) over 4 weeks but found no significant differences between the two groups in their respective reports. Li et al. (20) focused on eGFR at weeks 4, 12, and 48 and found that eGFR in the TDF and ETV groups declined differently at week 4 compared with baseline, and the decline in the TDF group was greater than that in the ETV group (− 5.83 vs − 4.75 ml/min/1.73m²). However, it is unclear whether the differences in nephrotoxicity are statistically significant. The study by Zhang et al. (19) reported that serum creatine and cystine C were increased in both TDF and ETV groups, but there was no significant difference between them. Furthermore, Wan et al. (21) found no patients with severe lactic acidosis or renal impairment due to ETV or TDF treatment during the 3-month follow-up, whereas Zhang et al. and Li et al. (20, 22) No renal-related adverse events, serious renal adverse events, or proximal tubulopathy events were observed during the 48-week follow-up period, and patients tolerated antiviral treatment well.

Sensitivity analysis and publication bias

We noted considerable heterogeneity in MELD scores and CTP scores at 12 weeks (Yo² = 94.7% and Yo² = 91.3%). Sensitivity analysis showed that the study by Hussain et al. is the main source of heterogeneity in the two combined analyses. After excluding this study and combining the analyzes again, no substantial changes were found in the above results, indicating that the results of the meta-analysis are stable.Furthermore, I² After removing data such as the 12-week survival rate from Wan et al., the value of the 12-week survival forest plot dropped from 55.7% to 28.3%. Begg’s test and Egger’s test found no notable publication bias, indicating that there is no significant publication bias (p= 0.91 (Begg’s test) (Fig. 6).