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

Suzuki, Kazuharu; Suda, Goki; Yamamoto, Yoshiya; Furuya, Ken; Baba, Masaru; Nakamura, Akinobu; Miyoshi, Hideaki; Kimura, Megumi; Maehara, Osamu; Yamada, Ryoichi; Kitagataya, Takashi; Yamamoto, Kōji; Shigesawa, Taku; Nakamura, Akihisa; Ohara, Masatsugu; Kawagishi, Naoki; Nakai, Masato; Sho, Takuya; Natsuizaka, Mitsuteru; Morikawa, Kenichi; Ogawa, Koji; Ohnishi, Shunsuke; Sakamoto, Naoya

doi:10.1007/s00535-020-01750-3

Cited by 34 publications

(40 citation statements)

References 46 publications

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“…In fact, we observed a lowering effect rather than less increase by TDF treatment in all lipid parameters, even in serum HDL-C. Another study may explain this effect that TDF decreased serum cholesterol levels by upregulating hepatic CD36 via PPARα activation. 44 It was previously reported that the incidence of metabolic syndrome, dyslipidaemia or abdominal obesity increases in CHB patients after virological response achieved. 45,46 Hence, it seems that the lowering dosage benefit by ProTide technology in TMF or tenofovir alafenamide deprived the lipid lowering effect of TDF at the same time.…”

Section: Discussionmentioning

confidence: 98%

Randomised clinical trial: 48 weeks of treatment with tenofovir amibufenamide versus tenofovir disoproxil fumarate for patients with chronic hepatitis B

Liu¹,

Jin²,

Zhang³

et al. 2021

Aliment Pharmacol Ther

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Background: Tenofovir amibufenamide (TMF) can provide more efficient delivery than tenofovir disoproxil fumarate (TDF).Aim: To compare the efficacy and safety of TMF and TDF for 48 weeks in patients with chronic hepatitis B (CHB). Methods:We performed a randomised, double-blind, non-inferiority study at 49 sites in China. Patients with CHB were assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo. The primary efficacy endpoint was the proportion of patients with hepatitis B virus (HBV) DNA less than 20 IU/mL at week 48. We also assessed safety, particularly bone, renal and metabolic abnormalities. Results:We randomised 1002 eligible patients. The baseline characteristics were well balanced between groups. After a median 48 weeks of treatment, the non-inferiority criterion was met in all analysis sets. In the HBeAg-positive population, 50.2% of patients receiving TMF and 53.7% receiving TDF achieved HBV DNA less than 20 IU/mL. In the HBeAgnegative population, 88.9% and 87.8%, respectively, achieved HBV DNA less than 20 IU/ mL in the TMF and TDF groups. Patients receiving TMF had significantly less decrease in bone mineral density at both hip (P < 0.001) and spine (P < 0.001), and a smaller increase in serum creatinine at week 48 (P < 0.05). Other safety results were similar between groups. Conclusion:TMF was non-inferior to TDF in terms of anti-HBV efficacy and showed better bone and renal safety. (NCT03903796).

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Section: Discussionmentioning

confidence: 98%

Randomised clinical trial: 48 weeks of treatment with tenofovir amibufenamide versus tenofovir disoproxil fumarate for patients with chronic hepatitis B

Liu¹,

Jin²,

Zhang³

et al. 2021

Aliment Pharmacol Ther

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“…Compared with patients treated with entecavir, greater declines in serum lipid components were observed in patients treated with TDF[ 70 ]. An in vitro study reported that TDF modulated lipid metabolism by upregulating hepatic CD36 by activating PPAR-α[ 71 ]. Overexpression of hepatic CD36 improved hepatic steatosis and insulin resistance by reducing hepatic lipids, which might explain the findings above.…”

Section: Effect Of Antiviral Treatment On Nafldmentioning

confidence: 99%

Chronic hepatitis B infection with concomitant hepatic steatosis: Current evidence and opinion

Shi¹,

Yang²,

Fan³

2021

WJG

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With the increasing incidence of obesity and metabolic syndrome worldwide, concomitant nonalcoholic fatty liver disease (NAFLD) in patients with chronic hepatitis B (CHB) has become highly prevalent. The risk of dual etiologies, outcome, and mechanism of CHB with concomitant NAFLD have not been fully characterized. In this review, we assessed the overlapping prevalence of metabolic disorders and CHB, assessed the risk of advanced fibrosis/hepatocellular carcinoma in CHB patients concomitant with NAFLD, and discussed the remaining clinical issues to be addressed in the outcome of such patients. We also explored the possible roles of hepatitis B virus in the development of steatosis and discussed difficultiesof histological evaluation. For CHB patients, it is important to address concomitant NAFLD through lifestyle management and disease screening to achieve better prognoses. The assessment of progressive changes and novel therapies for CHB patients concomitant with NAFLD deserve further research.

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“…Other factors, including aging and metabolic changes, may also be confounders that influence the emergence of of unfavorable outcomes during treatment with NUCs. A retrospective study was performed on HBV patients administered entecavir or tenofovir-disoproxil-fumarate, administration of tenofovir-disoproxil-fumarate, but not entecavir was associated with decreased serum cholesterol levels 29 . On the contrary, patients in the present study showed an increased mean triglyceride level, while their cholesterol levels remained stable.…”

Section: Discussionmentioning

confidence: 99%

Outcomes of Cessation of Antiviral Therapy in Chronic Hepatitis B: A Retrospective Cohort Study

Ergen¹,

Işık²,

Arslan³

et al. 2021

MMJ

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Objective: Data on the efficacy and duration of nucleos(t)ide analogue (NUC) therapies to prevent the development of cirrhosis and hepatocellular carcinoma in chronic hepatitis B (CHB) patients are scarce and heterogeneous. This study aimed to summarize the clinical and laboratory results of the patients with CHB infection who discontinued oral antiviral therapy. Methods: A single-centered cohort study was conducted with CHB infection. NUCs were discontinued in patients who were under viral suppression for at least two years with undetectable HBV DNA levels for 18 months. Risk factors for clinical relapse (CR) were evaluated. Results: A total of 77 patients were recruited. HBeAg status showed that 9.4% of the patients underwent HBeAg seroconversion with NUCs. HBeAg reversion was noted in four (31%) of these patients. Severe hepatitis, which resolved after antiviral therapy was restored, was reported in two out of 77 patients (4%). None of the patients with CR had clinical or biological signs of hepatic decompensation or died during the study period. Conclusions: We found no benefits of the discontinuation of antiviral therapy after viral suppression in patients with initially severe fibrotic HBV infection. In patients with mild to moderate fibrosis, cessation of antiviral treatment is not associated with adverse outcomes

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

Cited by 34 publications

References 46 publications

Randomised clinical trial: 48 weeks of treatment with tenofovir amibufenamide versus tenofovir disoproxil fumarate for patients with chronic hepatitis B

Randomised clinical trial: 48 weeks of treatment with tenofovir amibufenamide versus tenofovir disoproxil fumarate for patients with chronic hepatitis B

Chronic hepatitis B infection with concomitant hepatic steatosis: Current evidence and opinion

Outcomes of Cessation of Antiviral Therapy in Chronic Hepatitis B: A Retrospective Cohort Study

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