Sofosbuvir modulates the intimate relationship between hepatitis C virus and lipids

Romero‐Gómez, Manuel; Rojas, Ángela

doi:10.1002/hep.27581

Cited by 8 publications

(6 citation statements)

References 20 publications

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“…Interestingly, lipid levels changed to a more atherogenic profile with increase in TC, cLDL, apolipoprotein B, and lipoprotein-A, whereas endothelial dysfunction and subclinical atherosclerosis improved. This observation could be explained, at least, partly by: (i) lipid profiles that remain within the normal range; (ii) HCV ability to hijack lipid metabolism has given a “false” protective atherogenic profile that is restored after viral clearance; and (iii) the impact that HCV has on other CV risk factors such as insulin resistance (i.e., the improvement in the HOMA index) ( 25 – 29 ).…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C Virus Clearance by Direct-Acting Antivirals Agents Improves Endothelial Dysfunction and Subclinical Atherosclerosis: HEPCAR Study

Muñoz

Ampuero

Millán

et al. 2020

Clin Transl Gastroenterol

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INTRODUCTION: Hepatitis C virus (HCV) infection has been related to increased cardiovascular (CV) risk. The aim of this study was to analyze the impact of sustained virological response (SVR) on endothelial dysfunction and subclinical atherosclerosis in patients with hepatitis C virus treated with direct-acting antiviral agents. METHODS: A total of 114 patients were prospectively recruited and underwent CV risk assessment including (i) endothelial dysfunction determined through laser Doppler flowmetry and (ii) subclinical atherosclerosis, elucidated by the ankle-brachial index (ABI). Atherogenic lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides); markers of oxidative stress (oxidized low-density lipoprotein antibodies [OLAbs]), soluble markers of adhesion (vascular cell adhesion molecule [VCAM], e-selectin, and soluble markers of angiogenesis; and vascular endothelial growth factor, endothelial [EMPs] and platelet [PMPs] apoptotic microparticles, and cell-free DNA [cfDNA]) were measured. All determinations were performed at baseline, 12 weeks (SVR time), and 1 year after treatment. RESULTS: In patients with endothelial dysfunction, area of hyperemia improved after virus clearance ( P = 0.013) and was related to significant decrease in VCAM, e-selectin ( P < 0.001), and cfDNA ( P = 0.017) and to increased OLAb levels ( P = 0.001). In patients with subclinical atherosclerosis at baseline, a significantly improved ABI was seen after HCV clearance ( P < 0.001). Levels of both EMPs and PMPs also decreased after SVR and at follow-up ( P = 0.006 and P = 0.002, respectively). DISCUSSION: HCV clearance improved not only liver function but also endothelial dysfunction and subclinical atherosclerosis promoted by decrease in levels of VCAM, e-selectin, cfDNA, and PMPs and EMPs.

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Section: Discussionmentioning

confidence: 99%

Hepatitis C Virus Clearance by Direct-Acting Antivirals Agents Improves Endothelial Dysfunction and Subclinical Atherosclerosis: HEPCAR Study

Muñoz

Ampuero

Millán

et al. 2020

Clin Transl Gastroenterol

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“…This process may cause a decrease in the content of lipids in the blood, and DAA reverse the above process. When HCV is cleared, the lipids combined with HCV are released, which leads to an increase in the concentration of lipids in the blood [17,19] . The incidence of SAEs during the study period was 7.7% (25/326), none of which were related to the drug.…”

Section: Discussionmentioning

confidence: 99%

Alfosbuvir plus Daclatasvir for Treatment of Chronic Hepatitis C Virus Infection in China

Hua

Kong

et al. 2023

Preprint

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Background and aims A pan-genotypic and effective treatment regimen for patients with chronic hepatitis C virus (HCV) infection remains an unmet medical need in China. Alfosbuvir is a novel potent HCV NS5B polymerase inhibitor in development for the treatment of chronic HCV infection. We conducted a phase 3 study to evaluate the efficacy and safety of alfosbuvir in combination with daclatasvir in Chinese patients with HCV infection. Methods All patients received 600 mg alfosbuvir tablets plus 60 mg daclatasvir tablets once daily for 12 weeks. The primary endpoint was a sustained virologic response 12 weeks after the end of treatment (SVR12). A follow-up visit was done at week 4 and 12, and those who achieved SVR12 were followed up at post-treatment week 24. Results Of the 326 patients who received at least one dose of the study treatment, 321 (98.5% [95% CI 96.5–99.5%]) achieved SVR12, which was superior to the historical SVR12 rate of 88% (p < 0.0001). The SVR12 rates were similar regardless of most baseline characteristics. The most common adverse event (≥ 10%) was hypercholesterolemia. Serious adverse events (SAEs) were reported in 25 (7.7%) patients, none of which was judged to be related to the study treatment. The majority of adverse events (AEs) were mild to moderate in severity. Conclusions Alfosbuvir plus daclatasvir for 12 weeks was highly effective and safe in Chinese patients infected with HCV genotype 1, 2, 3, or 6, suggesting this regimen could be a promising option for HCV treatment in China irrespective of genotype.

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“…Interestingly, serum lipid profiles change in HCV-infected patients treated with direct-acting antivirals (DAA) and this correlates with viral clearance ( 205 , 206 ). Although direct evidence is missing, it is tempting to speculate that modulation of lipid metabolism associated to DAA contributes to viral clearance ( 207 ). In the case of HBV and HDV, metabolism could be manipulated on purpose with drugs to improve viral inhibition, to restore the immune response and finally to achieve functional cure.…”

Section: Discussionmentioning

confidence: 99%

What role for cellular metabolism in the control of hepatitis viruses?

Diaz

Vidalain²,

Ramière³

et al. 2022

Front. Immunol.

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Hepatitis B, C and D viruses (HBV, HCV, HDV, respectively) specifically infect human hepatocytes and often establish chronic viral infections of the liver, thus escaping antiviral immunity for years. Like other viruses, hepatitis viruses rely on the cellular machinery to meet their energy and metabolite requirements for replication. Although this was initially considered passive parasitism, studies have shown that hepatitis viruses actively rewire cellular metabolism through molecular interactions with specific enzymes such as glucokinase, the first rate-limiting enzyme of glycolysis. As part of research efforts in the field of immunometabolism, it has also been shown that metabolic changes induced by viruses could have a direct impact on the innate antiviral response. Conversely, detection of viral components by innate immunity receptors not only triggers the activation of the antiviral defense but also induces in-depth metabolic reprogramming that is essential to support immunological functions. Altogether, these complex triangular interactions between viral components, innate immunity and hepatocyte metabolism may explain why chronic hepatitis infections progressively lead to liver inflammation and progression to cirrhosis, fibrosis and hepatocellular carcinoma (HCC). In this manuscript, we first present a global overview of known connections between the innate antiviral response and cellular metabolism. We then report known molecular mechanisms by which hepatitis viruses interfere with cellular metabolism in hepatocytes and discuss potential consequences on the innate immune response. Finally, we present evidence that drugs targeting hepatocyte metabolism could be used as an innovative strategy not only to deprive viruses of key metabolites, but also to restore the innate antiviral response that is necessary to clear infection.

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Sofosbuvir modulates the intimate relationship between hepatitis C virus and lipids

Cited by 8 publications

References 20 publications

Hepatitis C Virus Clearance by Direct-Acting Antivirals Agents Improves Endothelial Dysfunction and Subclinical Atherosclerosis: HEPCAR Study

Hepatitis C Virus Clearance by Direct-Acting Antivirals Agents Improves Endothelial Dysfunction and Subclinical Atherosclerosis: HEPCAR Study

Alfosbuvir plus Daclatasvir for Treatment of Chronic Hepatitis C Virus Infection in China

What role for cellular metabolism in the control of hepatitis viruses?

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