Clin Mol Hepatol > Volume 30(4); 2024 > Article
Cheng and Yu: Reply to correspondence on “Cardiovascular risk in chronic hepatitis B patients treated with tenofovir disoproxil fumarate or tenofovir alafenamide”
Dear Editor,
We are grateful for the comments [1] from Prof. Hong and Prof. Choi to our Editorial [2]. The issue of risk of cardiovascular disease (CVD) of tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) treatment is based on the unexpected changes in lipid profiles in chronic hepatitis B (CHB). Current literature revealed controversial results between TAF treatment and lipid changes [3,4]. In contrast, lipid-lowering effects of TDF presented with lower levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol are well established [5,6]. Our previous study also showed that lower lipid profiles were observed in TDF-treated patients when compared with entecavir-treated patients [6]. How TDF works on lipid profiles is still unclear. Recently, we examined the lipid loading capacity of cholesterol and triglyceride in each very low-density lipoprotein (VLDL) and LDL-C particles [7] in CHB patients treated with TDF or entecavir. Comparing with entecavir-treated patients, reduced levels of apolipoprotein B100 (apo-B) in LDL particles but similar apo-B levels in VLDL particles were observed in TDF-treated patients (unpublished data). The results indicate that TDF treatment could enhance hepatic uptake of LDL by LDL receptor during the metabolized pathway of VLDL to LDL and subsequently lead to lower lipid profiles. However, how this feature works on lipids and the association with the long-term risk of CVD are still elusive. Finally, we totally agree that well-designed and prospective studies that address the association between the risk of CVD and long-term use of TDF or TAF are strongly required to validate the findings from Prof. Hong and Prof. Choi [8].

FOOTNOTES

Authors’ contribution
PN Cheng drafted the manuscript. ML Yu reviewed and finalized the manuscript.
Conflicts of Interest
The authors have no conflicts to disclose.

Abbreviations

CVD
cardiovascular disease
TDF
tenofovir disoproxil fumarate
TAF
tenofovir alafenamide
CHB
chronic hepatitis B
LDL-C
low-density lipoprotein cholesterol
VLDL
very low-density lipoprotein
apo-B
apolipoprotein B100

REFERENCES

1. Hong H, Choi J. Letter: Cardiovascular risk of tenofovir disoproxil fumarate or tenofovir alafenamide fumarate in patients with chronic hepatitis B: More questions than an answer - author’s reply. Clin Mol Hepatol 2024;30:272-273.
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2. Cheng PN, Yu ML. Cardiovascular risk of tenofovir disoproxil fumarate or tenofovir alafenamide in patients with chronic hepatitis B: More questions than an answer. Clin Mol Hepatol 2024;30:144-146.
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3. Lai RM, Lin S, Wang MM, Li N, Zhou JH, Lin XY, et al. Tenofovir alafenamide significantly increased serum lipid levels compared with entecavir therapy in chronic hepatitis B virus patients. World J Hepatol 2023;15:964-972.
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4. 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.
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5. 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.
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6. Cheng PN, Feng IC, Chen JJ, Kuo HT, Lee PL, Yu ML, et al. Body weight increase and metabolic derangements after tenofovir disoproxil fumarate switch to tenofovir alafenamide in patients with chronic hepatitis B. Aliment Pharmacol Ther 2024;59:230-238.
crossref pmid
7. Sun HY, Cheng PN, Tseng CY, Tsai WJ, Chiu YC, Young KC. Favouring modulation of circulating lipoproteins and lipid loading capacity by direct antiviral agents grazoprevir/elbasvir or ledipasvir/sofosbuvir treatment against chronic HCV infection. Gut 2018;67:1342-1350.
crossref pmid
8. Hong H, Choi WM, Lee D, Shim JH, Kim KM, Lim YS, et al. Cardiovascular risk in chronic hepatitis B patients treated with tenofovir disoproxil fumarate or tenofovir alafenamide. Clin Mol Hepatol 2024;30:49-63.
pmid

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