Hepatitis C virus eradication by direct-acting antiviral agents improves carotid atherosclerosis in patients with severe liver fibrosis

Petta, Salvatore; Adinolfi, Luigi Elio; Fracanzani, Anna Ludovica; Rini, Francesca; Caldarella, Rosalia; Calvaruso, V.; Cammà, Calogero; Ciaccio, Marcello; Marco, V. Di; Grimaudo, Stefania; Licata, Anna; Marrone, Aldo; Nevola, Riccardo; Pipitone, Rosaria Maria; Pinto, Antonio; Rinaldi, Luca; Torres, Daniele; Tuttolomondo, Antonino; Valenti, Luca; Fargion, Silvia

doi:10.1016/j.jhep.2018.02.015

Cited by 107 publications

(106 citation statements)

References 48 publications

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“…A recent study reported a significant decrease in carotid intima-media thickness measurement in HCV-infected persons with advanced fibrosis or compensated cirrhosis who were treated with a DAA regimen, suggesting a putative mechanism of CVD risk decrease. 39 Taken together, these observations strengthen the mounting evidence of the association between advanced liver fibrosis and CVD events and a significant decrease in such risk with treatment.…”

Section: March 2019supporting

confidence: 70%

Direct-Acting Antiviral Therapy for HCV Infection Is Associated With a Reduced Risk of Cardiovascular Disease Events

et al. 2019

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is associated with an increased risk of cardiovascular disease (CVD) events. It is not clear whether treatment with directacting antiviral (DAA) agents affects risk of CVD. METHODS:We searched the Electronically Retrieved Cohort of HCV-Infected Veterans database for patients with chronic HCV infection (n ¼ 242,680) and identified patients who had been treated with a pegylated interferon and ribavirin regimen (n ¼ 4436) or a DAA-containing regimen (n ¼ 12,667). Treated patients were matched for age, race, sex, and baseline values with patients who had never received treatment for HCV infection (controls). All subjects were free of any CVD event diagnosis of HCV infection at baseline. The primary outcome was incident CVD events, identified by International Classification of Diseases, Ninth Edition, Clinical Modification or International Classification of Diseases, Tenth Edition code, in the different groups and in patients with vs without a sustained virologic response to therapy. RESULTS: There were 1239 (7.2%) incident CVD events in the treated groups and 2361 (13.8%) events in the control group. Incidence rates were 30.9 per 1000 patient-years (95% CI 29.6-32.1) in the control group and 20.3 per 1000 patientyears (95% CI 19.2-21.5) in the treated groups (P < .0001). Treatment with pegylated interferon and ribavirin (hazard ratio 0.78; 95% CI 0.71-0.85) or a DAA regimen (hazard ratio 0.57; 95% CI 0.51-0.65) was associated with a significantly lower risk of a CVD event compared with no treatment (controls). Incidence rates for CVD events were 23.5 per 1000 patient-years (95% CI 21.8-25.3) in the group treated with the pegylated interferon and ribavirin regimen, 16.3 per 1000 patient-years (95% CI 14.7-18.0) in the group treated with a DAA regimen, and 30.4 (95% CI 29.2-31.7) in the control group. A sustained virologic response was associated with a lower risk of incident CVD events (hazard ratio 0.87; 95% CI 0.77-0.98). CONCLUSIONS: In an analysis of a cohort of HCV-infected veterans, treatment of HCV infection was associated with a significant decrease in risk of CVD events. Patients treated with a DAA regimen and patients who achieved sustained virologic responses had the lowest risk for CVD events.

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Section: March 2019supporting

confidence: 70%

Direct-Acting Antiviral Therapy for HCV Infection Is Associated With a Reduced Risk of Cardiovascular Disease Events

et al. 2019

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“…However, findings regarding vascular parameters following SVR that is achieved by DAA are inconsistent. One recent study measured and compared the intima thickness of the carotid artery at baseline and that 9‐12 months after the end of treatment . It enrolled 182 DAA‐treated CHC patients and all achieved SVR.…”

Section: Chronic Hepatitis Viral Infection and Arteriosclerosismentioning

confidence: 99%

“…One recent study measured and compared the intima thickness of the carotid artery at baseline and that 9-12 months after the end of treatment. 206 It enrolled 182 DAA-treated CHC patients and all achieved SVR. The intima thickness significantly decreased (0.94 ± 0.29 mm vs 0.81 ± 0.27, P < .001) and a significant reduction in the prevalence of carotid thickening from baseline to follow-up was observed (42.8% vs 17%, P < .001).…”

Section: Chroni C Hepatitis Vir Al Infec Ti On and Arteri Oscleros Ismentioning

confidence: 99%

Systematic review: chronic viral hepatitis and metabolic derangement

Wang

Cheng

Kao

2019

Aliment Pharmacol Ther

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Summary Background The liver has a critical role in the metabolism of glucose and lipids. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection leads to a spectrum of liver disease including chronic hepatitis, cirrhosis and hepatocellular carcinoma. Metabolic syndrome (MetS) has a rising incidence owing to an epidemic of type 2 diabetes mellitus (T2DM) and obesity. Non‐alcoholic fatty liver disease is a liver manifestation of MetS and has become the most common cause of chronic liver disease worldwide. Aim To summarise the interplay among hepatitis viruses, MetS and its components. Methods We searched the literature about HBV, HCV infection, MetS, fatty liver and its components from PubMed. Results With respect to the viral replication cycle, lipids are important mediators between viral entry and hepatocyte in HCV infection, but not in HBV infection. Thus, HCV infection is inversely associated with hyperlipidaemia and lipid rebound occurs following sustained viral response induced by interferon‐based therapy or direct antiviral agents. In addition, HCV infection is positively associated with insulin resistance, hepatic steatosis, MetS and the risk of T2DM and atherosclerosis. In contrast, HBV infection may protect infected subjects from the development of MetS and hepatic steatosis. Accumulating evidence suggests that HBV infection is inversely associated with lipid metabolism, and exhibits no conclusive association with insulin resistance or the risk of T2DM and arteriosclerosis. Conclusions In patients with viral hepatitis and concurrent metabolic diseases, a multidisciplinary approach should be given rather than simply antiviral treatment.

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“…A new and very important observation of the present study is the significant association between the procoagulant imbalance and the early atherosclerotic lesions, assessed by cIMT. Several studies pointed out that HCV infected subjects have a significantly high prevalence of early atherosclerosis despite being young and having a favourable cardiovascular risk profile, which improves after virus eradication . In line with this is the observation that viral eradication by the new DAA is followed by a reduction in early atherosclerosis alterations.…”

Section: Discussionmentioning

confidence: 99%

Procoagulant imbalance influences cardiovascular and liver damage in chronic hepatitis C independently of steatosis

Sigon

D’Ambrosio

Clerici

et al. 2019

Liver International

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Background & Aims:Patients with chronic HCV infection besides hepatitis often present cardiovascular damage, the pathogenesis of which is not defined. In chronic liver diseases, including NAFLD and cirrhosis, a procoagulant imbalance, potentially responsible for atherosclerosis has been reported. We aimed at evaluating whether a procoagulant imbalance is present also in non-cirrhotic patients with HCV infection and whether the procoagulant imbalance correlates with cardiovascular damage.The correlation between the procoagulant imbalance, coexisting steatosis, and liver fibrosis was analysed.Methods: From 2014 to 2018, 393 subjects (205 patients with chronic HCV infection from two liver units and 188 controls) were enrolled. Metabolic, cardiovascular, liver assessment and coagulation parameters-procoagulants (FII and FVIII) and anticoagulants (antithrombin and protein C [PC]), endogenous thrombin potential (ETP), peak-thrombin and their ratios (with/without thrombomodulin)-were determined. Results:The procoagulant imbalance (defined as high FVIII, FVIII/PC ratio, ETP-ratio and peak-thrombin-ratio (with/without thrombomodulin)) was significantly higher in patients with chronic HCV than controls. Steatosis was detected in 87 patients (42%).No difference in coagulation imbalance, carotid and cardiac parameters and severity of liver fibrosis was observed in patients with or without steatosis, despite the latter had less severe metabolic alterations. The FVIII/PC ratio was independently associated with carotid intima-media thickness (coefficient 0.04, 95% CI 0.002-0.07, P = .04) and liver fibrosis (coefficient 0.64, 95% CI 0.37-0.92, P < .0001). Conclusion: Patients with HCV infection, even in the absence of cirrhosis have a procoagulant-imbalance that possibly plays a role in increasing the risk of cardiovascular disease and progression of fibrosis. How to cite this article: Sigon G, D'Ambrosio R, Clerici M, et al. Procoagulant imbalance influences cardiovascular and liver damage in chronic hepatitis C independently of steatosis. Liver

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Hepatitis C virus eradication by direct-acting antiviral agents improves carotid atherosclerosis in patients with severe liver fibrosis

Cited by 107 publications

References 48 publications

Direct-Acting Antiviral Therapy for HCV Infection Is Associated With a Reduced Risk of Cardiovascular Disease Events

Direct-Acting Antiviral Therapy for HCV Infection Is Associated With a Reduced Risk of Cardiovascular Disease Events

Systematic review: chronic viral hepatitis and metabolic derangement

Procoagulant imbalance influences cardiovascular and liver damage in chronic hepatitis C independently of steatosis

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