Evidence map›Paper›PMID 33211179›Full record

ArticleJournal of gastroenterology2021

Tenofovir-disoproxil-fumarate modulates lipid metabolism via hepatic CD36/PPAR-alpha activation in hepatitis B virus infection.

Kazuharu Suzuki, Goki Suda, Yoshiya Yamamoto, Ken Furuya, Masaru Baba, Akinobu Nakamura, Hideaki Miyoshi, Megumi Kimura, Osamu Maehara, Ren Yamada and 14 more

Registry-linked trialAbstract read
PubMed Publisher
In one paragraph

Article in Journal of gastroenterology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05398393 (An Experimental Study on the Effect of Tenofovir Amibufenamide on Blood Lipid During Anti-HBV Treatment), which is not on this map. Cited by 39 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 2 pooled it
4.7field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05398393 naunknown statusnot on this mapstarted 2022, after this paper: background citation

An Experimental Study on the Effect of Tenofovir Amibufenamide on Blood Lipid During Anti-HBV Treatment

TypeinterventionalSponsorUnion Hospital, Tongji Medical College, Huazhong University of Science and TechnologyRan2022 to 2023Enrolled150ConditionsHepatitis B, Chronic, Lipid DisorderArmsoral Tenofovir Amibufenamide 25mg each day, lipid lowering drugs (e.g. Atorvastatin and amlodipine.)
3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 59 citations in OpenAlex.

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  12. Current status of drug therapy for chronic hepatitis B.World journal of gastroenterology · 2025
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  13. Observational
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  15. Review
  16. [Real-world study of tenofovir amibufenamide in the treatment of patients with hepatitis B cirrhosis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024
    Article
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  19. [Research progress of antiviral treatment for patients with chronic hepatitis B combined with metabolic fatty liver disease].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors at 2 institutions in 1 country.

Kazuharu Suzuki *Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Goki Suda *Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. gsudgast@pop.med.hokudai.ac.jp.ORCID 0000-0003-0098-9106
Yoshiya YamamotoDepartment of Gastroenterology, Hakodate Municipal Hospital, Hokkaido, Japan.
Ken FuruyaDepartment of Gastroenterology, JCHO Hokkaido Hospital, Hokkaido, Japan.
Masaru BabaDepartment of Gastroenterology, JCHO Hokkaido Hospital, Hokkaido, Japan.
Akinobu NakamuraDepartment of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Graduate School of Medicine, Hokkaido, Japan.
Hideaki MiyoshiDivision of Diabetes and Obesity, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Megumi KimuraDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Osamu MaeharaDepartment of Gastroenterology, Hakodate Municipal Hospital, Hokkaido, Japan.
Ren YamadaDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Takashi KitagatayaDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Koji YamamotoDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Taku ShigesawaDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Akihisa NakamuraDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Masatsugu OharaDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Naoki KawagishiDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Masato NakaiDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Takuya ShoDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Mitsuteru NatsuizakaDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Kenichi MorikawaDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Koji OgawaDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Shunsuke OhnishiDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Naoya SakamotoDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
NORTE Study Group
Hokkaido University · JPHokkaido hospital · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEntecavir and tenofovir-disoproxil-fumarate are first-line nucleos(t)ide analogs (NA) for treatment of hepatitis B virus (HBV) infections; however, their long-term administration can impact extrahepatic organs. Herein, we sought to examine the effect of NA on lipid metabolism while also characterizing the associated mechanism.

methodsA retrospective study was performed on HBV patients administered entecavir or tenofovir-disoproxil-fumarate. Patient clinical information, as well as their preserved serum samples obtained at baseline and 6-12 months after treatment initiation, were analyzed. A 1:1 propensity score matching was applied to the assignment of tenofovir-disoproxil-fumarate or entecavir treatment. Changes in serum cholesterol, including oxidized-LDL, were analyzed. Subsequently, in vitro analysis elucidated the mechanism associated with the effect of NAs on lipid metabolism.

resultsAdministration of tenofovir-disoproxil-fumarate, not entecavir, to chronic HBV patients, decreased serum cholesterol levels, including non-HDL and oxidized-LDL, which are strongly associated with arteriosclerosis. In vitro analysis revealed that tenofovir-disoproxil-fumarate reduced supernatant cholesterol, and upregulated the scavenger receptor, CD36, in hepatocytes. Meanwhile, silencing of hepatic CD36 increased supernatant cholesterol and negated the cholesterol-reducing effect of tenofovir-disoproxil-fumarate in HepG2-cells. Reporter, microarray, and RT-PCR analyses further revealed that tenofovir-disoproxil-fumarate treatment activates PPAR-α-mediated signaling, and upregulates PPAR-α target genes, including CPT1 and CD36. Alternatively, silencing of PPAR-α reversed the effects of tenofovir-disoproxil-fumarate on CD36.

conclusionsTenofovir-disoproxil-fumarate modulates lipid metabolism by upregulating hepatic CD36 via PPAR-α activation. Since dyslipidemia could be associated with arteriosclerosis and hepatocarcinogenesis, these discoveries provide novel insights into anti-HBV therapies, as well as the associated extrahepatic effects of NA.

Indexed as

AgedAntiviral AgentsFemaleHepatitis BHepatitis B virusHumansLipid MetabolismMaleMiddle AgedPPAR alphaRetrospective StudiesTenofovirAntiviral AgentsPPAR alphaTenofovirCD36Hepatitis B virusLipid metabolismOxidized LDLPPAR-alpha

Identifiers

PMID33211179
OpenAlexW3104225545

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.