Abstract
Background/Aims
The incidence and relapse pattern in patients stopping tenofovir alafenamide (TAF),
a prodrug of tenofovir which is more concentrated in hepatocytes, is unknown.
Methods
HBeAg-negative CHB patients stopping tenofovir disoproxil fumarate (TDF) (off-TDF)
or who had switched to TAF more than 3 months before discontinuation (off-TAF) were
recruited. The propensity score-matching method (PSM) was used, creating a ratio of
1:3 between the off-TAF versus the off-TDF groups to adjust for associated factors.
Results
After PSM, 180 off-TDF and 60 off-TAF patients were analyzed. The cumulative rates
of virological and clinical relapse at 52 weeks were 75.1% and 58.5% respectively
in the off-TDF group and 91.1% and 61.6% in the off-TAF group. Patients in the off-TAF
group had significantly higher rates of virological relapse than those in the off-TDF
group (p = 0.021), but not clinical relapse (p = 0.785). Multivariate cox regression analysis showed that off-TAF group was an independent
factor for virological relapse, but not clinical relapse. Severity of clinical relapse
and hepatic decompensation rate were comparable between off-TDF and off-TAF groups
Conclusions
The off-TAF group had a higher virological relapse rate than the off-TDF group. The difference in clinical relapse
pattern and severity was not clinically important between the two groups.
Keywords
Abbreviations:
ALT (alanine aminotransferase), CHB (chronic hepatitis B), CR (clinical relapse), EOT (end-of-treatment), HBV (hepatitis B virus), HBeAg (hepatitis B e antigen), HBsAg (hepatitis B surface antigen), NA (nucleoside analogues), TAF (tenofovir alafenamide), TDF (tenofovir disoproxil fumarate), ULN (upper limit of normal)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Digestive and Liver DiseaseAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Antiviral therapy for chronic hepatitis B viral infection in adults: a systematic review and meta-analysis.Hepatology. 2016; 63: 284-306
- Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update.Hepatol Int. 2016; 10: 1-98
- European Association for the Study of the L. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection.J Hepatol. 2017; 67: 370-398
- HBsAg seroclearance after nucleoside analogue therapy in patients with chronic hepatitis B: clinical outcomes and durability.Gut. 2014; 63: 1325-1332
- A comparison of 4-year entecavir efficacy in nucleos(t)ide analog-naive and -experienced adult Taiwanese chronic hepatitis B patients.Hepatol Int. 2013; 7: 832-843
- The times they are a-changing - A refined proposal for finite HBV nucleos(t)ide analog therapy.J Hepatol. 2021; 75: 474-480
- Incidence and predictors of hepatitis B surface antigen seroclearance after cessation of nucleos(t)ide analogue therapy in hepatitis B e antigen-negative chronic hepatitis B.Hepatology. 2018; 68: 425-434
- Association between level of hepatitis B surface antigen and relapse after entecavir therapy for chronic hepatitis B virus infection.Clin Gastroenterol Hepatol. 2015; 13: 1984-1992
- The incidence and predictors of HBV relapse after cessation of tenofovir therapy in chronic hepatitis B patients.J Viral Hepat. 2018; 25: 590-597
- Hepatitis B virus relapse rates in chronic hepatitis B patients who discontinue either entecavir or tenofovir.Aliment Pharmacol Ther. 2019; 49: 218-228
- Clinical relapse after cessation of tenofovir therapy in hepatitis B e antigen-negative patients.Clin Gastroenterol Hepatol. 2016; 14: 1813-1820
- contrasting timing of virological relapse after discontinuation of tenofovir or entecavir in hepatitis B e antigen-negative patients.J Infect Dis. 2018; 218: 1480-1484
- Distinct relapse rates and risk predictors after discontinuing tenofovir and entecavir therapy.J Infect Dis. 2018; 217: 1193-1201
- Mechanism for effective lymphoid cell and tissue loading following oral administration of nucleotide prodrug GS-7340.Mol Pharm. 2013; 10: 459-466
- 96Weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection.J Hepatol. 2018; 68: 672-681
- Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial.Lancet Gastroenterol Hepatol. 2016; 1: 196-206
- Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial.Lancet Gastroenterol Hepatol. 2016; 1: 185-195
- Clinical relapse pattern in HBeAg negative chronic hepatitis B can be changed by switching to another nucleos(t)ide analogues before cessation.Hepatology. 2020; 72: 478a-479a
- Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update.Hepatol Int. 2012; 6: 531-561
- Prevalence and clinical implications of hepatitis B virus genotypes in southern Taiwan.Scand J Gastroenterol. 2003; 38: 95-101
- Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group.Stat Med. 1998; 17: 2265-2281
- Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies.Pharmaceut Stat. 2011; 10: 150-161
- Associations of HBV genotype B vs C infection with relapse after cessation of entecavir or tenofovir therapy.Clin Gastroenterol Hepatol. 2020; 18: 2989-2997
- Enhancing the antihepatitis B virus immune response by adefovir dipivoxil and entecavir therapies.Cell Mol Immunol. 2011; 8: 75-82
- Implications of efficient hepatic delivery by tenofovir alafenamide (GS-7340) for hepatitis B virus therapy.Antimicrob Agents Chemother. 2015; 59: 3563-3569
- Hepatitis B virus-specific T cells associate with viral control upon nucleos(t)ide-analogue therapy discontinuation.J Clin Invest. 2018; 128: 668-681
- Clinical relapse after cessation of tenofovir therapy in hepatitis B e antigen–negative patients.Clin Gastroenterol Hepatol. 2016; 14: 1813-1820
Article info
Publication history
Published online: February 01, 2023
Accepted:
January 19,
2023
Received:
July 6,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
