Short-term and long-term safety and efficacy of tenofovir alafenamide, tenofovir disoproxil fumarate and entecavir treatment of acute-on-chronic liver failure associated with hepatitis B

Juan Li, Chunhua Hu, Yi Chen, Rou Zhang, Shan Fu, Mimi Zhou, Zhijie Gao, Mengjun Fu, Taotao Yan, Yuan Yang, Jianzhou Li, Jinfeng Liu, Tianyan Chen, Yingren Zhao, Yingli He, Juan Li, Chunhua Hu, Yi Chen, Rou Zhang, Shan Fu, Mimi Zhou, Zhijie Gao, Mengjun Fu, Taotao Yan, Yuan Yang, Jianzhou Li, Jinfeng Liu, Tianyan Chen, Yingren Zhao, Yingli He

Abstract

Background & aims: There is limited evidence on the efficacy and safety of nucleos(t) ide analogues (NAs) in the treatment of HBV-ACLF. Our objective was to evaluate the outcomes among TAF, TDF and ETV, three first-line antivirals against chronic hepatitis B, in patients with HBV-ACLF.

Methods: Patients with HBV-related ACLF were recruited and received daily TAF (25 mg/d), TDF (300 mg/d) and ETV (0.5 mg/d). They were prospectively followed-up. The primary endpoint was overall survival at week 12 and week 48, the secondary endpoints were virological response and biochemical response.

Results: Forty gender and age matched eligible subjects were recruited and divided into three groups: TAF group, TDF group and ETV group. By week 48, 8 (80%) patients in TAF group, 6 (60%) patients in TDF group and 17 (85%) patients in ETV group survived without liver transplantation (P = 0.251). After 4 weeks of NAs treatment, all three groups showed paralleling reduction of HBV DNA levels. All three groups presented similar biochemical responses at week 4, patients treated with TAF showed a priority in total bilirubin reduction, albumin and cholesterol maintenance. Additionally, although there was no significant difference in changes of serum urea, serum creatinine, serum cystatin C and estimated GFR among the three groups by treatment week 4, TDF showed unfavorable renal safety even in short -term treatment. The treatment using NAs was well-tolerated and there was no serious drug-related adverse event reported.

Conclusions: TAF, TDF and ETV are of similar efficacy and safety in short-term and long-term treatment of HBV-ACLF.

Trial registration: This study is ongoing and is registered with ClinicalTrials.gov , NCT03640728 (05/02/2019).

Keywords: Acute-on-chronic liver failure; Entecavir; Hepatitis B virus; Tenofovir alafenamide; Tenofovir disoproxil fumarate.

Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Fig. 1
Fig. 1
Patient disposition during the study. ACLF, acute-on-chronic liver failure; LAM, lamivudine; ETV, entecavir; TDF, tenofovir disoproxil fumarate; TAF, tenofovir alafenamide
Fig. 2
Fig. 2
Cumulative incidences of mortality during treatment with tenofovir alafenamide, tenofovir disoproxil fumarate and entecavir in patients with HBV-related ACLF. ETV, entecavir; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate
Fig. 3
Fig. 3
HBV-DNA reduction in serial mean HBV DNA by week 4 in the three groups. ETV, entecavir; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate
Fig. 4
Fig. 4
Dynamic changes in serial mean ALT (A), AST(B), total bilirubin(C), albumin(D), cholesterol (E), and MELD score (F) in patients treated with tenofovir alafenamide, tenofovir disoproxil fumarate and entecavir in patients with HBV-related ACLF. ETV, entecavir; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate; ALT, alanine aminotransferase; AST, aspartate Aminotransferase; MELD, Model for End-stage Liver Disease

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