Evaluation of the safety and antiviral efficacy of the tenofovir alafenamide fumarate molecule in immunosuppressed patients

Year 2022, , 1688 - 1692, 25.10.2022

Serdar Durak , Arif Mansur Coşar

https://doi.org/10.32322/jhsm.1179106

Cited By: 1

Abstract

Aim: Patients with chronic or prior hepatitis B virus (HBV) infection may experience HBV reactivation during immunosuppressive therapy. The objective of this study was to evaluate the safety and antiviral efficacy of tenofovir alafenamide fumarate (TAF) for prophylaxis of HBV reactivation in patients on immunosuppressive therapy.
Material and Method: This study included patients who were started on immunosuppressive treatment due to hematologic/solid malignancy, autoimmune disease, or inflammatory disease and were treated with TAF for at least six months due to HBsAg and/or total anti-HBc positivity at Karadeniz Technical University Farabi Hospital between January 2018 and February 2021. Electronic medical records were retrospectively reviewed and the adverse event profile was analyzed.
Results: Of the 94 patients enrolled in the study, 70.2% (n=66) were male. The mean age of the patients was 60.37±14.56 years. The reasons for initiation of immunosuppressive drug treatment were hematologic malignancies in 48.9% (n=46), solid tumors in 27.7% (n=26), and other causes (autoimmune/inflammatory) in 23.4% (n=22). There was no statistically significant difference in creatinine, phosphorus, glucose, and LDL profile between baseline and 6-12 months of TAF treatment (p=0.861, p=0.136, p=0.323, p=0.304, respectively). All patients in whom HBV DNA was detectable at baseline became negative at the last follow-up visit. None of the patients developed HBV reactivation and there was no need to discontinue antiviral/immunosuppressive treatment due to side effects.
Conclusion: TAF is a safe and effective short-term option to prevent HBV reactivation in patients receiving immunosuppressive therapy.

Keywords

Hepatitis B, chronic hepatitis B, reactivation, tenofovir alafenamide, chemotherapy, immunosuppression

References

• Kawsar HI, Shahnewaz J, Gopalakrishna K v, Spiro TP, Daw HA. Hepatitis B reactivation in cancer patients: role of prechemotherapy screening and antiviral prophylaxis. Clin Adv Hematol Oncol 2012; 10: 370-8.
• Pattullo V. Hepatitis B reactivation in the setting of chemotherapy and immunosuppression-prevention is better than cure. World J Hepatol 2015; 7: 954-67.
• Tozun N, Ozdogan O, Cakaloglu Y, et al. Seroprevalence of hepatitis B and C virus infections and risk factors in Turkey: a fieldwork TURHEP study. Clin Microbiol Infect 2015; 21: 1020-6.
• Ling WHY, Soe PP, Pang ASL, Lee SC. Hepatitis B virus reactivation risk varies with different chemotherapy regimens commonly used in solid tumours. Br J Cancer 2013; 108: 1931-5.
• Lau GK, Liang R, Chiu EK, Lee CK, Lam SK. Hepatic events after bone marrow transplantation in patients with hepatitis B infection: a case controlled study. Bone Marrow Transplant 1997; 19: 795-9.
• Dai MS, Wu PF, Shyu RY, Lu JJ, Chao TY. Hepatitis B virus reactivation in breast cancer patients undergoing cytotoxic chemotherapy and the role of preemptive lamivudine administration. Liver Int 2004; 24: 540-6.
• Lau G, Yu ML, Wong G, et al. APASL clinical practice guideline on hepatitis B reactivation related to the use of immunosuppressive therapy. Hepatol Int. 2021; 15: 1031-48.
• Agarwal K, Brunetto M, Seto WK, et al. 96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection. J Hepatol 2018; 68: 672-81.
• Casado JL. Renal and bone toxicity with the use of tenofovir: understanding at the end. AIDS Rev [Internet] 2016; 18: 59-68.
• European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2017; 67: 370-98.
• Gill US, Zissimopoulos A, Al-Shamma S, et al. Assessment of bone mineral density in tenofovir-treated patients with chronic hepatitis B: can the fracture risk assessment tool identify those at greatest risk? J Infect Dis 2015; 211: 374-82.
• Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018; 67: 1560-99.
• Aygen B, Demir AM, Gumus M, et al. Immunosuppressive therapy and the risk of hepatitis B reactivation: Consensus report. Turk J Gastroenterol 2018; 29; 259-69.
• Reddy KR, Beavers KL, Hammond SP, Lim JK, Falck-Ytter YT, American Gastroenterological Association Institute. American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology 2015; 148: 215-9; quiz e16-7.
• Hwang JP, Somerfield MR, Alston-Johnson DE, et al. Hepatitis B virus screening for patients with cancer before therapy: American Society of Clinical Oncology Provisional Clinical Opinion Update. J Clin Oncol 2015; 33: 2212-20.
• Yang C, Qin B, Yuan Z, Chen L, Zhou HY. Meta-analysis of prophylactic entecavir or lamivudine against hepatitis B virus reactivation. Ann Hepatol 15: 501-11.
• Picardi M, della Pepa R, Giordano C, et al. Tenofovir vs lamivudine for the prevention of hepatitis B virus reactivation in advanced-stage DLBCL. Blood 2019; 133: 498-501.
• Sax PE, Gallant JE, Klotman PE. Renal safety of tenofovir disoproxil fumarate. AIDS Read 2007; 17: 90-2, 99-104, C3.
• Gallant JE, Winston JA, DeJesus E, et al. The 3-year renal safety of a tenofovir disoproxil fumarate vs. a thymidine analogue-containing regimen in antiretroviral-naive patients. AIDS. 2008; 22: 2155-63.
• Ray AS, Fordyce MW, Hitchcock MJM. Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of Human Immunodeficiency Virus. Antiviral Res 2016; 125: 63-70.
• Agarwal K, Fung SK, Nguyen TT, et al. Twenty-eight day safety, antiviral activity, and pharmacokinetics of tenofovir alafenamide for treatment of chronic hepatitis B infection. J Hepatol 2015; 62: 533-40.
• Chen YC, Su YC, Li CY, Hung SK. 13-year nationwide cohort study of chronic kidney disease risk among treatment-naïve patients with chronic hepatitis B in Taiwan. BMC Nephrol 2015; 16: 110.
• Randell PA, Jackson AG, Zhong L, Yale K, Moyle GJ. The effect of tenofovir disoproxil fumarate on whole-body insulin sensitivity, lipids and adipokines in healthy volunteers. Antivir Ther 2010; 15: 227-33.
• Santos JR, Saumoy M, Curran A, et al. The lipid-lowering effect of tenofovir/emtricitabine: a randomized, crossover, double-blind, placebo-controlled trial. Clin Infect Dis 2015; 61: 403-8.
• Shaheen AA, AlMattooq M, Yazdanfar S, et al. Tenofovir disoproxil fumarate significantly decreases serum lipoprotein levels compared with entecavir nucleos(t)ide analogue therapy in chronic hepatitis B carriers. Aliment Pharmacol Ther 2017; 46: 599-604.
• Mallon PWG, Brunet L, Fusco JS, et al. Lipid changes after switch from TDF to TAF in the OPERA Cohort: LDL cholesterol and triglycerides. Open Forum Infect Dis 2022; 9: ofab621.
• Squillace N, Ricci E, Menzaghi B, et al. The effect of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) on liver enzymes, glucose, and lipid profile. Drug Des Devel Ther 2020; 14: 5515-20.
• Li ZB, Li L, Niu XX, et al. Switching from entecavir to tenofovir alafenamide for chronic hepatitis B patients with low-level viraemia. Liver Int 2021; 41: 1254-64.