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Risk of dyslipidemia in chronic hepatitis B patients taking tenofovir alafenamide: a systematic review and meta-analysis

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A Letter to the Editor to this article was published on 02 March 2024

Abstract

Background

The aim of this study was to demonstrate how tenofovir alafenamide (TAF) and other hepatitis B treatment drugs differentially impact lipid profiles in chronic hepatitis B patients.

Methods

We searched PubMed, Ovid MEDLINE, EMBASE, and the Cochrane Library to identify studies on the changes in cholesterol level in hepatitis B patients who underwent TAF therapy. The changes in lipid profiles (e.g., HDL-c, LDL-c, total cholesterol [TC], and triglyceride [TG]) were compared between the TAF treatment group and the baseline, other nucleoside analogs (NAs), and tenofovir disoproxil fumarate (TDF)-only treatment groups. In addition, risk factors for worsening cholesterol level when treated with TAF were examined.

Results

Twelve studies involving 6,127 patients were selected. After 6 months of TAF treatment, LDL-c, TC, and TG were increased by 5.69 mg/dL, 7.89 mg/dL, and 9.25 mg/dL, respectively, from the baseline level. In particular, with the treatment of TAF, levels of LDL, TC, and TG rose by 8.71 mg/dL, 18.34 mg/dL, and 13.68 mg/dL, respectively, showing a greater deterioration of cholesterol when the TAF treatment was implemented compared to other NAs (e.g., TDF or entecavir). When TAF was compared to TDF, LDL-c, TC, and TG worsened with a mean difference of 14.52 mg/dL, 23.72 mg/dL, and 14.25 mg/dL, respectively. As a result of a meta-regression analysis, risk factors for worsening lipid profiles were found to be treatment-experienced, previous diabetes, and hypertension.

Conclusions

TAF continues to worsen lipid profiles including LDL-c, TC, and TG after 6 months of use compared to the other NAs.

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Availability of data and materials

The data sets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Lau G, Marcellin P, Peters M. Chronic hepatitis B: a global health problem requiring coherent worldwide treatment strategies. Hepatol Int. 2007;1:316–325

    Article  PubMed  PubMed Central  Google Scholar 

  2. Ringelhan M, McKeating JA, Protzer U. Viral hepatitis and liver cancer. Philos Trans R Soc Lond B Biol Sci. 2017;372:20160274

    Article  PubMed  Google Scholar 

  3. Collaborators GBDHB. Global, regional, and national burden of hepatitis B, 1990–2019: a systematic analysis for the global burden of disease study 2019. Lancet Gastroenterol Hepatol. 2022;7:796–829

    Article  Google Scholar 

  4. 2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. J Korean Liver Cancer Stud Group 2022;0.

  5. Renne SL, Tommaso LD. A clinical and pathological update on hepatocellular carcinoma. J Liver Cancer. 2022;22:14–22

    Article  PubMed  PubMed Central  Google Scholar 

  6. Korean Association for the Study of the L. KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol. 2022;28:276–331

    Article  Google Scholar 

  7. Meireles LC, Marinho RT, Van Damme P. Three decades of hepatitis B control with vaccination. World J Hepatol. 2015;7:2127–2132

    Article  PubMed  PubMed Central  Google Scholar 

  8. Oh H, Jun DW, Lee IH, Ahn HJ, Kim BO, Jung S, et al. Increasing comorbidities in a South Korea insured population-based cohort of patients with chronic hepatitis B. Aliment Pharmacol Ther. 2020;52:371–381

    Article  PubMed  Google Scholar 

  9. Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560–1599

    Article  PubMed  Google Scholar 

  10. Lee BT, Chang M, Lim C, Bae HS, Fong TL. Bone and renal safety profile at 72 weeks after switching to tenofovir alafenamide in chronic hepatitis B patients. JGH Open. 2021;5:258–263

    Article  PubMed  Google Scholar 

  11. Lagoutte-Renosi J, Flammang M, Chirouze C, Beck-Wirth G, Bozon F, Brunel AS, et al. Real-life impact on lipid profile of a switch from tenofovir disoproxil fumarate to tenofovir alafenamide in HIV-infected patients. Curr HIV Res. 2021;19:84–89

    Article  CAS  PubMed  Google Scholar 

  12. Plum PE, Maes N, Sauvage AS, Frippiat F, Meuris C, Uurlings F, et al. Impact of switch from tenofovir disoproxil fumarate-based regimens to tenofovir alafenamide-based regimens on lipid profile, weight gain and cardiovascular risk score in people living with HIV. BMC Infect Dis. 2021;21:910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Buti M, Gane E, Seto WK, Chan HL, Chuang WL, Stepanova T, et al. 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

    Article  PubMed  Google Scholar 

  14. Jeong J, Shin JW, Jung SW, Park EJ, Park NH. Tenofovir alafenamide treatment may not worsen the lipid profile of chronic hepatitis B patients: A propensity score-matched analysis. Clin Mol Hepatol. 2022;28:254–264

    Article  PubMed  Google Scholar 

  15. Kim SY, Park JE, Lee YJ, Seo HJ, Sheen SS, Hahn S, et al. Testing a tool for assessing the risk of bias for nonrandomized studies showed moderate reliability and promising validity. J Clin Epidemiol. 2013;66:408–414

    Article  PubMed  Google Scholar 

  16. Cai S, Ou Z, Liu D, Liu L, Liu Y, Wu X, et al. Risk factors associated with liver steatosis and fibrosis in chronic hepatitis B patient with component of metabolic syndrome. United European Gastroenterol J. 2018;6:558–566

    Article  PubMed  PubMed Central  Google Scholar 

  17. Cho Y, Cho EJ, Yoo JJ, Chang Y, Chung GE, Jeong SM, et al. Association between lipid profiles and the incidence of hepatocellular carcinoma: a nationwide population-based study. Cancers (Basel). 2021;13:1599

    Article  CAS  PubMed  Google Scholar 

  18. Wang H, Lu X, Yang X, Xu N. The efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate in antiretroviral regimens for HIV-1 therapy: meta-analysis. Medicine (Baltimore). 2016;95: e5146

    Article  CAS  PubMed  Google Scholar 

  19. Pilkington V, Hughes SL, Pepperrell T, McCann K, Gotham D, Pozniak AL, et al. Tenofovir alafenamide vs tenofovir disoproxil fumarate: an updated meta-analysis of 14 894 patients across 14 trials. AIDS. 2020;34:2259–2268

    Article  PubMed  Google Scholar 

  20. Cid-Silva P, Fernandez-Bargiela N, Margusino-Framinan L, Balboa-Barreiro V, Mena-De-Cea A, Lopez-Calvo S, et al. Treatment with tenofovir alafenamide fumarate worsens the lipid profile of HIV-infected patients versus treatment with tenofovir disoproxil fumarate, each coformulated with elvitegravir, cobicistat, and emtricitabine. Basic Clin Pharmacol Toxicol. 2019;124:479–490

    Article  CAS  PubMed  Google Scholar 

  21. Mallon PWG, Brunet L, Fusco JS, Prajapati G, Beyer A, Fusco GP, 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

    Article  PubMed  Google Scholar 

  22. Suzuki K, Suda G, Yamamoto Y, Abiko S, Kinoshita K, Miyamoto S, et al. Effect of switching from tenofovir disoproxil fumarate to tenofovir alafenamide on lipid profiles in patients with hepatitis B. PLoS ONE. 2022;17: e0261760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Brunet L, Mallon P, Fusco JS, Wohlfeiler MB, Prajapati G, Beyer A, et al. Switch from tenofovir disoproxil fumarate to tenofovir alafenamide in people living with HIV: lipid changes and statin underutilization. Clin Drug Investig. 2021;41:955–965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Zhang Y, Li Z, Luo Q, Xu W, Wang L, Zhu S, et al. Changes in blood lipids in patients with chronic hepatitis B after 48 weeks of tenofovir alafenamide treatment: A prospective real-world clinical study. Antivir Ther. 2022;27:13596535221082400

    Article  CAS  Google Scholar 

  25. Lin HY, Tseng TC. Dyslipidemia in chronic hepatitis B patients on tenofovir alafenamide: facts and puzzles. Clin Mol Hepatol. 2022;28:181–182

    Article  PubMed  PubMed Central  Google Scholar 

  26. Shaheen AA, AlMattooq M, Yazdanfar S, Burak KW, Swain MG, Congly SE, 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

    Article  CAS  PubMed  Google Scholar 

  27. Mallon PW, Brunet L, Hsu RK, Fusco JS, Mounzer KC, Prajapati G, et al. Weight gain before and after switch from TDF to TAF in a U.S. cohort study. J Int AIDS Soc. 2021;24: e25702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kuo PH, Sun HY, Chuang YC, Wu PY, Liu WC, Hung CC. Weight gain and dyslipidemia among virally suppressed HIV-positive patients switching to co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide. Int J Infect Dis. 2020;92:71–77

    Article  CAS  PubMed  Google Scholar 

  29. Lampertico P, Buti M, Fung S, Ahn SH, Chuang WL, Tak WY, et al. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in virologically suppressed patients with chronic hepatitis B: a randomised, double-blind, phase 3, multicentre non-inferiority study. Lancet Gastroenterol Hepatol. 2020;5:441–453

    Article  PubMed  Google Scholar 

  30. Mills A, Arribas JR, Andrade-Villanueva J, DiPerri G, Van Lunzen J, Koenig E, et al. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in antiretroviral regimens for virologically suppressed adults with HIV-1 infection: a randomised, active-controlled, multicentre, open-label, phase 3, non-inferiority study. Lancet Infect Dis. 2016;16:43–52

    Article  CAS  PubMed  Google Scholar 

  31. Suzuki K, Suda G, Yamamoto Y, Furuya K, Baba M, Nakamura A, et al. Tenofovir-disoproxil-fumarate modulates lipid metabolism via hepatic CD36/PPAR-alpha activation in hepatitis B virus infection. J Gastroenterol. 2021;56:168–180

    Article  CAS  PubMed  Google Scholar 

  32. Silverstein RL, Febbraio M. CD36, a scavenger receptor involved in immunity, metabolism, angiogenesis, and behavior. Sci Signal. 2009;2:re3

    Article  PubMed  PubMed Central  Google Scholar 

  33. Koonen DP, Jacobs RL, Febbraio M, Young ME, Soltys CL, Ong H, et al. Increased hepatic CD36 expression contributes to dyslipidemia associated with diet-induced obesity. Diabetes. 2007;56:2863–2871

    Article  CAS  PubMed  Google Scholar 

  34. Luangrath V, Brodeur MR, Rhainds D, Brissette L. Mouse CD36 has opposite effects on LDL and oxidized LDL metabolism in vivo. Arterioscler Thromb Vasc Biol. 2008;28:1290–1295

    Article  CAS  PubMed  Google Scholar 

  35. Brundert M, Heeren J, Merkel M, Carambia A, Herkel J, Groitl P, et al. Scavenger receptor CD36 mediates uptake of high density lipoproteins in mice and by cultured cells. J Lipid Res. 2011;52:745–758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Lacey A, Savinelli S, Barco EA, Macken A, Cotter AG, Sheehan G, et al. Investigating the effect of antiretroviral switch to tenofovir alafenamide on lipid profiles in people living with HIV. AIDS. 2020;34:1161–1170

    Article  CAS  PubMed  Google Scholar 

  37. Wang Y, Xiong J, Niu M, Chen X, Gao L, Wu Q, et al. Statins and the risk of cirrhosis in hepatitis B or C patients: a systematic review and dose-response meta-analysis of observational studies. Oncotarget. 2017;8:59666–59676

    Article  PubMed  PubMed Central  Google Scholar 

  38. Goh MJ, Sinn DH, Kim S, Woo SY, Cho H, Kang W, et al. Statin use and the risk of hepatocellular carcinoma in patients with chronic hepatitis B. Hepatology. 2020;71:2023–2032

    Article  CAS  PubMed  Google Scholar 

  39. Li X, Sheng L, Liu L, Hu Y, Chen Y, Lou L. Statin and the risk of hepatocellular carcinoma in patients with hepatitis B virus or hepatitis C virus infection: a meta-analysis. BMC Gastroenterol. 2020;20:98

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Gilbert JM, Vest K, Kish TD. Long-term evaluation of changes in kidney function after switching from tenofovir disoproxil fumarate to tenofovir alafenamide in patients living with HIV. Pharmacy (Basel). 2022;10:164

    Article  PubMed  Google Scholar 

  41. van den Berg E, Kloppenborg RP, Kessels RP, Kappelle LJ, Biessels GJ. Type 2 diabetes mellitus, hypertension, dyslipidemia and obesity: a systematic comparison of their impact on cognition. Biochim Biophys Acta. 2009;1792:470–481

    Article  PubMed  Google Scholar 

  42. Halpern A, Mancini MC, Magalhaes ME, Fisberg M, Radominski R, Bertolami MC, et al. Metabolic syndrome, dyslipidemia, hypertension and type 2 diabetes in youth: from diagnosis to treatment. Diabetol Metab Syndr. 2010;2:55

    Article  PubMed  PubMed Central  Google Scholar 

  43. Chan HL, Fung S, Seto WK, Chuang WL, Chen CY, Kim HJ, et al. 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

    Article  PubMed  Google Scholar 

  44. Lim J, Choi WM, Shim JH, Lee D, Kim KM, Lim YS, et al. Efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate in treatment-naïve chronic hepatitis B. Liver Int. 2022;42:1517–1527

    Article  CAS  PubMed  Google Scholar 

  45. Li J, Hu C, Chen Y, Zhang R, Fu S, Zhou M, et al. 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. BMC Infect Dis. 2021;21:567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Hosaka T, Suzuki F, Kobayashi M, Fujiyama S, Kawamura Y, Sezaki H, et al. Renal safety and biochemical changes for 2 years after switching to tenofovir alafenamide from long-term other nucleotide analog treatment in patients with chronic hepatitis B. Hepatol Res. 2022;52:153–164

    Article  CAS  PubMed  Google Scholar 

  47. Akdemir Kalkan I, Karasahin O, Sarigul F, Altunisik Toplu S, Aladag M, Akgul F, et al. Comparison of tenofovir alafenamide and entecavir therapy in patients with chronic hepatitis B initially treated with tenofovir disoproxil. Retrosp Obs Surv. 2021;21: e118721

    Google Scholar 

  48. Karasahin O, Kalkan IA, Dal T, Toplu SA, Harputoğlu M, Mete AO, et al. Real-life data for tenofovir alafenamide fumarate treatment of hepatitis B: the pythagoras cohort. Hepat Mon. 2021;21:1–9

    Google Scholar 

  49. Ogawa E, Nakamuta M, Koyanagi T, Ooho A, Furusyo N, Kajiwara E, et al. Switching to tenofovir alafenamide for nucleos(t)ide analogue-experienced patients with chronic hepatitis B: week 144 results from a real-world, multi-centre cohort study. Aliment Pharmacol Ther. 2022;56:713–722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Jeong S, Shin HP, Kim HI. Real-world single-center comparison of the safety and efficacy of entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide in patients with chronic hepatitis B. Intervirology. 2022;65:94–103

    Article  CAS  PubMed  Google Scholar 

  51. Byun KS, Choi J, Kim JH, Lee YS, Lee HC, Kim YJ, et al. Tenofovir alafenamide for drug-resistant hepatitis B: A randomized trial for switching from tenofovir disoproxil fumarate. Clin Gastroenterol Hepatol. 2022;20:427-437.e425

    Article  CAS  PubMed  Google Scholar 

  52. Agarwal K, Brunetto M, Seto WK, Lim YS, Fung S, Marcellin P, et al. weeks treatment of tenofovir alafenamide vs tenofovir disoproxil fumarate for hepatitis B virus infection. J Hepatol. 2018;68:672–681

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to thank Jae-Young Kim in Research Factory Inc. (rfactory.kr) for consulting the statistical analysis

Funding

This work was supported by the Soonchunhyang University Research Fund.

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Authors and Affiliations

  1. Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyaung University College of Medicine, Bucheon, Republic of Korea

    Eui Gwon Hwang, Jeong-Ju Yoo, Sang Gyune Kim & Young Seok Kim

  2. Department of Medical Library, Soonchunhyang University Bucheon Hospital, Soonchunhyaung University College of Medicine, Bucheon, Republic of Korea

    Eun-Ae Jung

  3. Department of Gastroenterology and Hepatology, Digestive Research Center and Liver Clinic, Soonchunhyang Bucheon Hospital, 170 Jomaruro Wonmigu, Bucheonsi Gyeonggido, 14584, Republic of Korea

    Jeong-Ju Yoo

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Contributions

Study concept and design: J-JY; provision of study materials or patients: J-JY, E-AJ; collection and assembly of data: SGK, YSK; data analysis and interpretation: EGH, J-JY; manuscript writing: EGH; final approval of manuscript: all authors.

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Correspondence to Jeong-Ju Yoo.

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The authors (Eui Gwon Hwang, Eun-Ae Jung, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim) have no relevant financial or non-financial interests to disclose.

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Ethics approval was waived from the Institutional Review Board and our study conformed to the ethical guidelines of the World Medical Association Declaration of Helsinki.

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Hwang, E.G., Jung, EA., Yoo, JJ. et al. Risk of dyslipidemia in chronic hepatitis B patients taking tenofovir alafenamide: a systematic review and meta-analysis. Hepatol Int 17, 860–869 (2023). https://doi.org/10.1007/s12072-023-10528-7

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  • DOI: https://doi.org/10.1007/s12072-023-10528-7

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