Clin Mol Hepatol > Volume 28(2); 2022 > Article
Lin and Tseng: Dyslipidemia in chronic hepatitis B patients on tenofovir alafenamide: Facts and puzzles
Most chronic hepatitis B (CHB) patients need to stay in indefinite nucleos(t)ide analogue (NA) treatment to reduce hepatitis B virus (HBV)-related complications as HBV could only be contained but not cured by NA [1]. Tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) are two potent NAs and TAF is favored over TDF due to less renal and bone toxicities [2]. However, deterioration of lipid profile has been shown after switching from TDF- to TAF-containing antiretroviral regimens in human immunodeficiency virus (HIV) infected patients in both clinical trials and real-world data [3,4]. Since dyslipidemia is associated with cardiovascular disease and metabolic/non-alcoholic associated fatty liver disease, and the latter could increase hepatocellular carcinoma risks, it should be clarified whether TAF therapy alone deteriorates lipid profile in CHB patients.
In this study, Jeong et al. [5] applied propensity score-matching to compare the changes of lipid profile among CHB patients receiving TAF or TDF, inactive CHB, and non-HBV infected control groups in a follow-up period of 48 weeks. The results showed a significant decrease of serum total cholesterol (TC) level in the TDF group when compared with TAF (156.7±27.7 vs. 176.3±32.9, P<0.001) and non-HBV infected (156.2±28.3 vs. 175.0±29.5, P<0.001) group. In contrast, comparable lipid profiles were identified among TAF group, inactive CHB, and non-HBV infected control groups. The authors concluded that TAF is a lipid-neutral agent as the alterations of lipid profile were comparable between TAF and control groups. In contrast, TDF is potentially associated with lipid-lowering effect.
Jeong et al. [5] further postulated that the higher circulating tenofovir concentration in TDF users than that in TAF users might explain the results. Their theory was supported by another paper from Canada in which lower lipids were observed in TDF group when compared with the entecavir group in CHB patients [6]. However, the underlying mechanism remains unclear.
Although this study shows that TAF may be lipid-neutral in CHB patients without dyslipidemia, several issues need to be addressed. First, the effect of TAF on CHB patients with dyslipidemia remains unknown as they were excluded in this study. In a retrospective, observational, multicenter study targeting HIV patients, no significant increment of TC level was found in TAF group if the patient had underlying hyperlipidemia [7]. More studies are needed to address the issue. Nevertheless, physicians should keep a close eye on patients with lipid levels near the upper limit of normal when switching from TDF to TAF. Second, even if switching from TDF to TAF causes more patients developing dyslipidemia, there are multiple potent lipid-lowering agents available. The benefit of lipid-lowering effect of TDF should not outweigh the risks of welldocumented bone and kidney adverse events.
In summary, this well-designed study indicates that TAF itself could be a lipid-neutral rather than a lipid-increasing agent. Physicians should monitor the lipid profile more closely in their patients when switching their TDF with TAF. Future studies with longer follow-up periods and broader patient inclusion criteria to explore cardiovascular outcomes, together with the findings of this research, may impact the way CHB patients are managed.

FOOTNOTES

Authors’ contributions
Conception: TC Tseng; Drafting of the manuscript: HY Lin; Critical review of the manuscript: HY Lin and TC Tseng
Conflicts of Interest
Hung-Yao Lin declares no conflict of interest. Tai-Chung Tseng has served on speaker’s bureaus for Fujirebio, Bristol-Myers Squibb, and Gilead Sciences and received grant support from Gilead Sciences.

Abbreviations

CHB
chronic hepatitis B
HBV
hepatitis B virus
HCC
hepatocellular carcinoma
HIV
human immunodeficiency virus
NA
nucleos(t)ide analogue
TAF
tenofovir alafenamide
TC
total cholesterol
TDF
tenofovir disoproxil fumarate

REFERENCES

1. Tseng TC, Kao JH. Elimination of hepatitis B: is it a mission possible? BMC Med 2017;15:53.
crossref pmid pmc
2. Liang LY, Wong GL. Unmet need in chronic hepatitis B management. Clin Mol Hepatol 2019;25:172-180.
crossref pmid pmc
3. Hagins D, Orkin C, Daar ES, Mills A, Brinson C, DeJesus E, et al. Switching to coformulated rilpivirine (RPV), emtricitabine (FTC) and tenofovir alafenamide from either RPV, FTC and tenofovir disoproxil fumarate (TDF) or efavirenz, FTC and TDF: 96-week results from two randomized clinical trials. HIV Med 2018;19:724-733.
crossref pmid pmc
4. Kauppinen KJ, Kivelä P, Sutinen J. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide significantly worsens the lipid profile in a real-world setting. AIDS Patient Care STDS 2019;33:500-506.
crossref pmid
5. 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.
crossref
6. 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.
crossref pmid
7. Taramasso L, Di Biagio A, Riccardi N, Briano F, Di Filippo E, Comi L, et al. Lipid profile changings after switching from rilpivirine/tenofovir disoproxil fumarate/emtricitabine to rilpivirine/tenofovir alafenamide/emtricitabine: different effects in patients with or without baseline hypercholesterolemia. PLoS One 2019;14:e0223181.
crossref pmid pmc

Editorial Office
The Korean Association for the Study of the Liver
Room A1210, 53 Mapo-daero(MapoTrapalace, Dowha-dong), Mapo-gu, Seoul, 04158, Korea
TEL: +82-2-703-0051   FAX: +82-2-703-0071    E-mail: kasl@kams.or.kr
Copyright © The Korean Association for the Study of the Liver.         
COUNTER
TODAY : 677
TOTAL : 823329
Close layer