Anthropometric parameters and liver histology influence lipid metabolic changes in HCV chronic hepatitis on direct-acting antiviral treatment

Iossa, Domenico; Vitrone, Martina; Gagliardi, Massimo; Falco, Erasmo; Ragone, Enrico; Zampino, Rosa; Durante‐Mangoni, Emanuele

doi:10.21037/atm-20-669

Cited by 12 publications

(28 citation statements)

References 41 publications

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“…Observed cardiovascular events consisted of two patients developing MI at the end of treatment and at the one-year follow-up, respectively, both with non-decreasing FIB-4 scores. Stable cholesterol levels, despite the increased use of statins, is coherent with previous data showing increased cholesterol levels after HCV eradication [ 22 , 26 , 27 ]. The effect of statin on fibrosis levels is yet to be clarified; however, some studies showed an association of the former with decreased inflammation and fibrosis [ 52 , 53 ].…”

Section: Discussionsupporting

confidence: 88%

“…DAAs were shown to reduce CHC hepatic complications, overall mortality, and need for liver transplantation [ 6 , 12 , 21 ]. However, the effect on CHC-associated CVD is not as clear [ 22 ]. Several studies showed reduced CVD, including acute coronary syndrome, atherosclerosis, and type 2 diabetes, with DAA treatment and SVR, as compared to no treatment or no SVR [ 23 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

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Cardiovascular Risk in Patients with Chronic Hepatitis C Treated with Direct Acting Antivirals

Ramadan

Boccia

Moretto

et al. 2022

JCM

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Background: Chronic hepatitis C (CHC) is associated with hepatic and extrahepatic complications, including cardiovascular disease (CVD). The effects of sustained virological response (SVR) and liver fibrosis on CVD risk are not well established. Aims: We aim to assess the dynamics of Fibrosis-4 (FIB-4) and Atherosclerotic Cardiovascular Disease 2013 (ASCVD) scores up to three years after direct acting antivirals (DAA) treatment and explore the time-dependent association between the two scores. Methods: We included consecutive CHC patients treated with DAA and followed up with them for three years. Outcomes were changes from baseline (before DAA) in ASCVD and FIB-4 scores, measured at the end of treatment, 12-, 24-, and 36-months follow-up. Results: In total, 91 patients with CHC were finally included (median age: 66 years (IQR = 58–72 years); 43% females). Median follow-up was 2 years (1–3 years) and all patients reached SVR. The ASCVD score did not significantly change from baseline (Mean = 17.2%, 95% CI 14.1, 20.3), but the FIB-4 score significantly decreased at any time-point by an average of 0.8 (95% CI 0.78, 0.82, p < 0.001). Elevated FIB-4 scores at one (β = 1.16, p < 0.001) and three years (β = 2.52, p < 0.001) were associated with an increased ASCVD score. Clinically, two participants- with non-decreasing FIB-4 scores after treatment- had acute coronary syndrome at the end of treatment and one year follow-up, respectively. Conclusions: In our study, we found that FIB-4 and ASCVD scores exhibited a positive correlation irrespective of time-point after treatment. Larger studies are essential to further investigate the utility of FIB-4 scores in cardiovascular risk assessment.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Cardiovascular Risk in Patients with Chronic Hepatitis C Treated with Direct Acting Antivirals

Ramadan

Boccia

Moretto

et al. 2022

JCM

Self Cite

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“…DAA therapy, which efficiently compromises HCV replication, caused a rapid rise of LDL levels in patients with a sustained virologic response in various studies [128,[131][132][133][134][135][136] (Figure 2). It remains unclear if DAA-mediated viral elimination alters PCSK9 levels in circulation.…”

Section: Pcsk9 and Hcv-induced Chronic Liver Diseasementioning

confidence: 99%

“…However, the decline of LDL argues for a higher functionality of the hepatic LDL-R. Efficient elimination of HCV rapidly increased circulating LDL, whereas PCSK9 levels most likely decline [126,128,129,[131][132][133][134][135][136]. Hepatic expression levels of LDL-R, PCSK9, VLDL-R and SR-B1 after viral eradication are still unknown.…”

Section: Pcsk9 and Hcv-induced Chronic Liver Diseasementioning

confidence: 99%

Emerging Insights on the Diverse Roles of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Chronic Liver Diseases: Cholesterol Metabolism and Beyond

Grewal

Buechler

2022

IJMS

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Chronic liver diseases are commonly associated with dysregulated cholesterol metabolism. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease of the proprotein convertase family that is mainly synthetized and secreted by the liver, and represents one of the key regulators of circulating low-density lipoprotein (LDL) cholesterol levels. Its ability to bind and induce LDL-receptor degradation, in particular in the liver, increases circulating LDL-cholesterol levels in the blood. Hence, inhibition of PCSK9 has become a very potent tool for the treatment of hypercholesterolemia. Besides PCSK9 limiting entry of LDL-derived cholesterol, affecting multiple cholesterol-related functions in cells, more recent studies have associated PCSK9 with various other cellular processes, including inflammation, fatty acid metabolism, cancerogenesis and visceral adiposity. It is increasingly becoming evident that additional roles for PCSK9 beyond cholesterol homeostasis are crucial for liver physiology in health and disease, often contributing to pathophysiology. This review will summarize studies analyzing circulating and hepatic PCSK9 levels in patients with chronic liver diseases. The factors affecting PCSK9 levels in the circulation and in hepatocytes, clinically relevant studies and the pathophysiological role of PCSK9 in chronic liver injury are discussed.

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“…Many researchers have reported recovery from HCV-induced hypolipidaemia after DAA treatment [ 66 , 67 , 68 , 69 , 70 ]. However, most studies showed that ANGPTL-targeted lipid species, such as triglycerides and VLDL cholesterol, remained the same before and after DAA treatment, even at 24-week follow-ups [ 66 , 67 , 68 , 71 ]. Alternatively, a moderate post-cure increase was noted only in patients with mild fibrosis [ 70 ].…”

Section: Discussionmentioning

confidence: 99%

Differential Expression of the Host Lipid Regulators ANGPTL-3 and ANGPTL-4 in HCV Infection and Treatment

Valiakou

Eliadis

Karamichali

et al. 2021

IJMS

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Host lipid metabolism reprogramming is essential for hepatitis C virus (HCV) infection and progression to severe liver disease. Direct-acting antivirals (DAAs) achieve a sustained virological response (SVR) in most patients, but virus eradication does not always protect against hepatocellular carcinoma (HCC). Angiopoietin-like protein-3 (ANGPTL-3) and angiopoietin-like protein-4 (ANGPTL-4) regulate the clearance of plasma lipids by inhibiting cellular lipase activity and possess emerging roles in tumourigenesis. We used ELISA and RT-qPCR to investigate ANGPTL-3 and ANGPTL-4 expression in HCV patients with characterised fibrosis throughout the natural history of hepatitis C and in long-term HCV infection in vitro, before and after DAA treatment. ANGPTL-3 was decreased in patients with advanced fibrosis compared to other disease stages, while ANGPTL-4 was progressively increased from acute infection to cirrhosis and HCC, peaking at the advanced fibrosis stage. Only ANGPTL-3 mRNA was down-regulated during early infection in vitro, although both ANGPTLs were increased later. DAA treatment did not alter ANGPTL-3 levels in advanced fibrosis/cirrhosis and in HCV infection in vitro, in contrast to ANGPTL-4. The association between ANGPTLs and fibrosis in HCV infection was underlined by an inverse correlation between the levels of ANGPTLs and serum transforming growth factor- β (TGF-β). Collectively, we demonstrate the pivotal role of advanced fibrosis in defining the expression fate of ANGPTLs in HCV infection and after treatment and propose a role for ANGPTL-3 as a contributor to post-treatment deregulation of lipid metabolism that could predispose certain individuals to HCC development.

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Anthropometric parameters and liver histology influence lipid metabolic changes in HCV chronic hepatitis on direct-acting antiviral treatment

Cited by 12 publications

References 41 publications

Cardiovascular Risk in Patients with Chronic Hepatitis C Treated with Direct Acting Antivirals

Cardiovascular Risk in Patients with Chronic Hepatitis C Treated with Direct Acting Antivirals

Emerging Insights on the Diverse Roles of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Chronic Liver Diseases: Cholesterol Metabolism and Beyond

Differential Expression of the Host Lipid Regulators ANGPTL-3 and ANGPTL-4 in HCV Infection and Treatment

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