The effect of sustained virological response by direct-acting antivirals on insulin resistance and diabetes mellitus in patients with chronic hepatitis C

Adinolfi, Luigi Elio; Rinaldi, Luca; Marrone, Aldo; Giordano, Mauro

doi:10.1080/14787210.2018.1505500

Cited by 14 publications

(12 citation statements)

References 14 publications

(20 reference statements)

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“…This finding is consistent with a recent report that treatment even without SVR reduced risk of stroke in a large sample of US veterans, although these analyses were based on time‐dependent treatment variables among a HCV cohort that was not limited to patients with T2D. Likewise, our overall findings are consistent with a recent meta‐analysis that showed decreased risk in a number of extrahepatic outcomes among HCV patients who achieved SVR, although this analysis was also not limited to patients with diabetes, as well as a review that reported improvement across a number of metabolic parameters among diabetic patients …”

Section: Discussionsupporting

confidence: 91%

Sustained virological response to hepatitis C treatment decreases the incidence of complications associated with type 2 diabetes

Gordon

Rupp

et al. 2019

Aliment Pharmacol Ther

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Background:The role of hepatitis C (HCV) eradication on the long-term complications of type 2 diabetes mellitus remains incompletely studied.Aim: To investigate whether antiviral treatment impacted risk of acute coronary syndrome, end-stage renal disease, ischaemic stroke, and retinopathy among diabetic patients from the four US health systems comprising the Chronic Hepatitis Cohort Study (CHeCS). Methods:We included CHeCS HCV patients with diagnosis codes for type 2 diabetes who were on antidiabetic medications. Patients were followed until an outcome of interest, death, or last health system encounter. The effect of treatment on outcomes was estimated using the competing risk analysis (Fine-Gray subdistribution hazard ratio [sHR]), with death as a competing event.Results: Among 1395 HCV-infected patients with type 2 diabetes, 723 (52%) were treated with either interferon-based or direct-acting antivirals (DAAs); 539 (75% of treated) achieved sustained virological response (SVR). After propensity score adjustment to address treatment selection bias, patients with SVR demonstrated significantly decreased risk of acute coronary syndrome (sHR = 0.36; P < 0.001), end-stage renal disease (sHR = 0.46; P < 0.001), stroke (sHR = 0.34; P < 0.001), and retinopathy (sHR = 0.24; P < 0.001) compared to untreated patients. Results were consistent in subgroup analyses of DAA-treated patients and interferon-treated patients, an analysis of cirrhotic patients, as well as in sensitivity analyses considering cause-specific hazards, exclusion of patients with on-treatment retinopathy, and treatment status as a time-varying covariate.Conclusion: Successful HCV treatment among patients with type 2 diabetes significantly reduces incidence of acute coronary syndrome, end-stage renal disease, ischaemic stroke, and retinopathy, regardless of cirrhosis. Our findings support the importance of HCV antiviral therapy among patients with type 2 diabetes to reduce the risk of these extrahepatic outcomes.The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

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Section: Discussionsupporting

confidence: 91%

Sustained virological response to hepatitis C treatment decreases the incidence of complications associated with type 2 diabetes

Gordon

Rupp

et al. 2019

Aliment Pharmacol Ther

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“…in glucose metabolism. It has been showed that SVR by DAAs causes a significant reduction in the risk of developing diabetes [29]. Overall data show that the clearance of HCV by DAAs improves pro-atherogenic metabolic factors.…”

Section: Discussionmentioning

confidence: 86%

“…There is a wide literature supporting that HCV infection increases the subclinical and clinical risk of CV diseases [2][3][4][5][6][7][8][9][10][11] through multiple direct and indirect proatherogenic immune and inflammatory mechanisms, metabolic alterations (insulin resistance, diabetes) and a direct cardiovascular tropism of HCV [27]. Some studies evaluated the effect of clearance of HCV by DAAs on pro-atherosclerosis metabolic alterations [20,28,29]. An analysis of a large population of HCV patients treated with DAAs showed that those who achieved SVR had a significant improvement in some CV risk biomarkers [28].…”

Section: Discussionmentioning

confidence: 99%

“…Our study did not investigate the mechanisms involved in reducing CV risk after HCV clearance. Literature data reported that the clearance of HCV by DAA improves atherosclerosis and pro-atherogenic metabolic, inflammatory and immunological conditions and therefore should reduce the risk of CV events [20,[28][29][30]. The reduction of inflammation is a possible mechanism.…”

Section: Discussionmentioning

confidence: 99%

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Impact of hepatitis C virus clearance by direct-acting antiviral treatment on the incidence of major cardiovascular events: A prospective multicentre study

et al. 2020

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“…Several studies have assessed the impact of HCV clearance by DAAs on metabolic conditions considered pro-atherosclerosis[ 20 - 22 ]. A recent post-hoc analysis was conducted using a large populations of patients with chronic hepatitis C genotype 1 infection and treated with DAA (3D) ± ribavirin (RBV) in order to evaluate the impact of treatment on cardiovascular and metabolic markers during a follow-up period of 52 wk post-treatment[ 20 ].…”

Section: Daa Impact On Hcv-related Atherosclerosismentioning

confidence: 99%

Chronic hepatitis C, atherosclerosis and cardiovascular disease: What impact of direct-acting antiviral treatments?

Adinolfi¹,

Rinaldi²,

Nevola³

2018

WJG

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Hepatitis C virus (HCV) infection is associated with extrahepatic manifestations, among these there is an increased risk of atherosclerosis and cardiovascular disease as well as an increased cardiovascular mortality. Several direct and indirect HCV pro-atherogenic mechanisms have been proposed. HCV lives and replicates within carotid plaques, promoting a local environment of pro-atherogenic factors. In addition, it causes conditions such as insulin resistance, diabetes, hepatic steatosis, cryoglobulinemia and endotoxinemia that are associated with the development of atherosclerosis and cardiovascular disease. Therapeutic regimens based on direct-acting antiviral agents (DAA) are currently available with high efficacy in HCV clearance and improvement of liver disease, but does HCV eradication also improve atherosclerosis and the risk of cardiovascular disease? Recently, a multi-center study has shown that elimination of HCV improves carotid atherosclerosis. Two studies have shown that DAA treatments significantly reduce the risk of cardiovascular events. Several studies have assessed the impact of HCV clearance on pro-atherosclerosis metabolic conditions showing improvement in cardiovascular risk biomarkers, disappearance or improvement of insulin resistance, reduction of risk of developing diabetes and improvement of glycemic control. There are also evidences that HCV clearance promotes the recovery of cytokines and inflammatory markers associated with atherosclerosis and the disappearance of cryoglobulinemia. Available data show that clearance of HCV by DAAs is associated with an improvement in atherosclerosis and metabolic and immunological conditions that promote the development of cardiovascular disease. However, the data are not sufficient to allow definitive conclusions and further studies will be needed to definitively clarify the impact of HCV clearance on atherosclerosis and cardiovascular disease.

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The effect of sustained virological response by direct-acting antivirals on insulin resistance and diabetes mellitus in patients with chronic hepatitis C

Cited by 14 publications

References 14 publications

Sustained virological response to hepatitis C treatment decreases the incidence of complications associated with type 2 diabetes

Sustained virological response to hepatitis C treatment decreases the incidence of complications associated with type 2 diabetes

Impact of hepatitis C virus clearance by direct-acting antiviral treatment on the incidence of major cardiovascular events: A prospective multicentre study

Chronic hepatitis C, atherosclerosis and cardiovascular disease: What impact of direct-acting antiviral treatments?

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