Efficacy and safety of tenofovir disoproxil fumarate versus entecavir in the treatment of acute-on-chronic liver failure with hepatitis B: a systematic review and meta-analysis

Abstract

Background: Oral nucleoside (acid) analogues (NAs) are recommended for patients with acute-on-chronic liver failure (ACLF) associated with hepatitis B virus (HBV-ACLF). The efficacy and safety of tenofovir (TDF) and entecavir (ETV) in these patients remain unclear.

Methods: A comprehensive literature search in PubMed, Web of Science, The Cochrane Library, and Embase database was conducted to select studies published before December 2022 on TDF or ETV for HBV-ACLF. The primary outcomes were survival rates at 4, 12, and 48 weeks. Secondary outcomes were virologic and biochemical responses, serum antigen conversion, liver function score, and safety.

Results: Four prospective and one retrospective cohort studies were selected. The overall analysis showed comparable survival rates at 4, 12, and 48 weeks for all patients receiving TDF or ETV (4-week: RR = 1.17, 95% CI: 0.90-1.51, p = 0.24; 12-week: RR = 1.00, 95% CI: 0.88-1.13, p = 0.94; 48-week: RR = 0.96, 95% CI: 0.58-1.57, p = 0.86). Child-Turcotte-Pugh (CTP) score and model for end-stage liver disease (MELD) score at 12 weeks were comparable in both groups but lower than baseline (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). At 48 weeks, estimated glomerular filtration rate (eGFR) levels were found to decrease to different degrees from baseline in both the TDF and ETV groups, and the decrease was greater in the TDF group than in the ETV group. No significant differences were found in biochemical, virologic response, and serum antigen conversion between the two groups during the observation period.

Conclusion: TDF treatment of HBV-ACLF is similar to ETV in improving survival, liver function, and virologic response but the effects on renal function in two groups in the long term remain unclear. More and larger long-term clinical trials are required to confirm these findings.

Keywords: Acute-on-chronic liver failure; Entecavir; Hepatitis B virus; Meta-analysis; Tenofovir; Therapy.

Fig. 1

Identification process for eligible studies. The 95 studies initially identified from our electronic search met the inclusion criteria and were included in this meta-analysis

Fig. 2

Survival rates at 4, 12, and 48 weeks for TDF and ETV in all included studies

Fig. 3

A Reduced HBV DNA levels of TDF and ETV at 2 weeks. B HBV DNA clearance rate of TDF and ETV at 12 weeks

Fig. 4

A Alanine aminotransferase levels at 4 weeks after TDF and ETV therapy. B Total bilirubin levels at 4 weeks after TDF and ETV therapy

Fig. 5

A CTP score for TDF and ETV therapy. B MELD score for TDF and ETV therapy

Fig. 6

Begg’s test of survival rate at 12 weeks. The horizontal line in the funnel plot indicates the fixed effects summary estimates, while the diagonal line indicates the expected 95% confidence interval given the standard errors, assuming no heterogeneity between studies. Publication bias was not observed in studies using Egger’s (p = 0.91) test, suggesting no evidence of publication bias