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Averta C, Mancuso E, Spiga R, Miceli S, Succurro E, Fiorentino TV, Perticone M, Mannino GC, Thamtarana PJ, Sciacqua A, Sesti G, Andreozzi F. The Functional Polymorphism of DDAH2 rs9267551 Is an Independent Determinant of Arterial Stiffness. Front Cardiovasc Med 2022; 8:811431. [PMID: 35047582 PMCID: PMC8761764 DOI: 10.3389/fcvm.2021.811431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 11/29/2021] [Indexed: 12/03/2022] Open
Abstract
Background: The association of circulating asymmetric dimethylarginine (ADMA) levels with cardiovascular risk and arterial stiffness has been reportedly demonstrated, although the causal involvement of ADMA in the pathogenesis of these conditions is still debated. Dimethylaminohydrolase 2 (DDAH2) is the enzyme responsible for ADMA hydrolysis in the vasculature, and carriers of the polymorphism rs9267551 C in the 5′-UTR of DDAH2 have been reported to have higher DDAH2 expression and reduced levels of serum ADMA. Approach and Results: We genotyped rs9267551 in 633 adults of European ancestry and measured their carotid–femoral pulse wave velocity (cfPWV), the gold-standard method to estimate arterial stiffness. cfPWV resulted significantly lower in rs9267551 C allele carriers (Δ = −1.12 m/s, P < 0.01) after correction for age, sex and BMI, and a univariate regression showed that the presence of rs9267551 C variant was negatively associated with cfPWV (β = −0.110, P < 0.01). In a multivariable regression model, subjects carrying the rs9267551 C allele manifested significantly lower cfPWV than GG carriers (β = −0.098, P = 0.01) independently from several potential confounders. We measured circulating ADMA levels in a subset of 344 subjects. A mediation analysis revealed that the effect of DDAH2 rs9267551 genotype on cfPWV was mediated by the variation in ADMA levels. Conclusions: These evidences hint that the presence of rs9267551 C allele may explain, at least in part, a reduction in vessel rigidity as measured by cfPWV, and support the attribution of a causative role to ADMA in the pathogenesis of arterial stiffness.
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Affiliation(s)
- Carolina Averta
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Elettra Mancuso
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Rosangela Spiga
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Sofia Miceli
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Elena Succurro
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
- Research Center for the Prevention and Treatment of Metabolic Diseases (CR METDIS), University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Teresa Vanessa Fiorentino
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Maria Perticone
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Gaia Chiara Mannino
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
- *Correspondence: Gaia Chiara Mannino
| | - Prapaporn Jungtrakoon Thamtarana
- Siriraj Center of Research Excellence for Diabetes and Obesity, Division of Molecular Medicine, Department of Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Angela Sciacqua
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
- Research Center for the Prevention and Treatment of Metabolic Diseases (CR METDIS), University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Giorgio Sesti
- Department of Clinical and Molecular Medicine, University of Rome-Sapienza, Rome, Italy
| | - Francesco Andreozzi
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
- Research Center for the Prevention and Treatment of Metabolic Diseases (CR METDIS), University Magna Graecia of Catanzaro, Catanzaro, Italy
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Zhou D, Yan M, Tang S, Feng Y. Association of Nondiabetic Glucometabolic Status and Aortic Stiffness in Community Hypertension Patients. Diabetes Metab Syndr Obes 2022; 15:591-600. [PMID: 35241918 PMCID: PMC8887139 DOI: 10.2147/dmso.s356488] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 02/11/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Diabetes is most commonly associated with aortic stiffness, but the importance of nondiabetic glucometabolic status for aortic stiffness (AS) in hypertension patients is unclear. METHODS We included 1065 hypertension patients without diabetes in a cohort study. Carotid-femoral pulse wave velocity (cfPWV) >10 m/s can broadly be defined as AS. Pearson correlation analysis and multiple regression analysis are used to reveal the relationship between elevated fasting blood glucose (FBG) and AS. RESULTS The 1065 hypertension patients (mean age 60 years) included 48% male, 22% smokers, 94.3% with anti-hypertensive drugs, 17.9% with AS, 80% with abdominal obesity, 42% with elevated triglycerides (TG), and 27% with elevated FBG. The mean values for office systolic blood pressure (SBP)/diastolic blood pressure (DBP) and central SBP/DBP were 130/85mmHg and 132/86mmHg. Mean cfPWV was 8.7m/s. Multiple regression analysis revealed that age, office SBP, and elevated FBG were independently related to AS in the whole hypertension. Elevated FBG had 1.6-fold risk of AS in hypertension patients compared with below the cutoff. In subgroup analysis, elevated FBG increased 2.68-fold risk for AS in those without metabolic syndrome (MS), not in MS. The area under curve (AUC) of office SBP was higher than central SBP for AS in receiver operating characteristic (ROC) analysis. CONCLUSION We found that elevated FBG was an independent risk factor for AS in hypertension patients without MS, although there was a high proportion of abdominal obesity. Office SBP was better than central SBP to assess AS in community hypertension.
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Affiliation(s)
- Dan Zhou
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China
| | - Mengqi Yan
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China
| | - Songtao Tang
- Department of Internal Medicine, Community Health Center of Liaobu Community, Dongguan, People’s Republic of China
| | - Yingqing Feng
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China
- Correspondence: Yingqing Feng, Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, No. 106 Zhongshan Two Road, Yuexiu District, Guangzhou, 510080, People’s Republic of China, Email
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Impact of sustained virological response on metabolic disorders in diabetic chronic hepatitis C virus patients after treatment with generic sofosbuvir and daclatasvir. Eur J Gastroenterol Hepatol 2021; 33:1588-1594. [PMID: 32804853 DOI: 10.1097/meg.0000000000001903] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES To evaluate the effect of generic sofosbuvir and daclatasvir (SOF/DCV) treatment on the glycemic state and insulin resistance as well as lipid profiles of those who achieved sustained virological response (SVR) in diabetic chronic hepatitis C virus (CHC) patients. METHODS We retrospectively reviewed 114 CHC patients with evidence of type 2 diabetes that were treated with generic SOF/DCV between May 2016 and August 2017. Baseline demographic and laboratory data were recorded. At 12-week post end of therapy (SVR12), glycemic state and insulin resistance as well as lipid profiles were re-evaluated and compared with baseline. RESULTS A total of 98 diabetic CHC patients were finally included and were responders. A significant decline in the glycemic state as well as Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) values (P ≤ 0.0001) was observed, but HOMA-S showed a statistically significant increase (P ≤ 0.0001) at SVR12 in comparison to baseline values. Also, a significant increase in serum total cholesterol, low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol levels was observed at SVR12 compared to baseline, but serum triglycerides levels showed a significant decrease. Logistic regression showed that the higher baseline HOMA-IR was a significant predictive variable of a decrease ≥20% of HOMA-IR, while higher baseline HOMA-IR and baseline triglycerides emerged as the only significant predictors of the Δ increase LDL-C level at SVR12. CONCLUSION SOF/DCV-based therapy led to an improvement of glycemic state associated with a global worsening of lipid profile. Further studies are strongly warranted to evaluate the cardiovascular balance between amelioration of insulin resistance and negative changes of the lipid profile.
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Isaac A, El-Mageed KHA, Kaisar HH, Rasmy HS, Ghait RSAE, Ibrahim IM, Riad GS. Assessment of serum Resistin in detecting Insulin Resistance and their impact on response to direct acting antiviral in chronic viral hepatitis C patients. EGYPTIAN LIVER JOURNAL 2021. [DOI: 10.1186/s43066-021-00136-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Chronic hepatitis C (CHC) virus is associated with insulin resistance and diabetes which have been linked to progressive liver fibrosis and sustained virologic response (SVR) to antiviral treatment. Resistin is a polypeptide hormone belonging to adipokines that may contribute to the development of obesity, insulin resistance, and metabolic syndrome. Also, the link between resistin and insulin resistance in patients with chronic hepatitis C and the effect of new direct acting antivirals on them seems unclear at present. The aim of this study is to evaluate the role of Resistin in detecting Insulin Resistance and their impact on response to direct acting antiviral in chronic hepatitis C patients.
Results
The Study was prospective Cohort clinical study, in Hepatology outpatient clinic at Ain Shams University Hospitals .This study was performed on 40 Egyptian patients who have Chronic viral hepatitis C, divided into 3 groups: GROUP I includes: 20 patients with Chronic viral hepatitis C on Sofosbovir- Daclatasvir before start of treatment and Sustained viral response after 12 weeks [SVR 12]. GROUP II includes: 20 patients with Chronic viral hepatitis C and non-responders before start of 2nd line of treatment and SVR 12. GROUP III includes: 10 subjects not infected with HCV as control group. The following investigations were done: body mass index calculation, Laboratory investigations including CBC, complete hepatic function tests, FIB-4 calculation, fasting serum insulin, HOMA-IR and serum Resistin level at baseline and re-assessed 12 weeks post end of treatment. Fasting serum Insulin, HOMA-IR and Resistin level were statistically significant higher in both naïve & relapser chronic HCV infected patients than in control group (p value <0.001). SVR 12 weeks post treatment was achieved in all 40 patients received new direct acting antivirals with a Significant reduction in Fasting serum Insulin, HOMA-IR and Resistin level at SVR 12 week (p value 0,001, <0.001, <0.001) respectively. Significant positive correlation was found between Resistin level and HOMA-IR in both naïve and relapse chronic HCV patients. Calculation of FIB-4 among patients showed significant higher FIB-4 in naïve patients than relapser (p value 0,002). Serum Resistin at a cut off value >1800 ng/ml had 38.89 % sensitivity, 86.36 % specificity, 70 % PPV, 63.3 % NPV (with an overall accuracy of 57.1 %) in predicting absence of liver cirrhosis based on FIB-4. And at a cutoff value ≥2400 ng/ml had 93.55% sensitivity, 33.3% specificity, 82.9% positive predictive value, and 60% negative predictive value with an overall accuracy of 62.4% in prediction of significant insulin resistance among chronic HCV patients.
Conclusion
Serum Resistin level was significantly up regulated in patients with chronic HCV, with significant reduction in its level after achievement of SVR. Resistin has the potential to be a biomarker for screening of insulin resistance among chronic HCV patients.
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Impact of DAA-Based Regimens on HCV-Related Extra-Hepatic Damage: A Narrative Review. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1323:115-147. [PMID: 33326112 DOI: 10.1007/5584_2020_604] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Two-third of patients with chronic hepatitis C show extrahepatic manifestations due to HCV infection of B lymphocytes, such as mixed cryoglobulinemia and non-Hodgkin B-cell lymphoma, or develop a chronic inflammatory status that may favor the development of adverse cardiovascular events, kidney diseases or metabolic abnormalities.DAAs treatments induce HCV eradication in 95% of treated patients, which also improves the clinical course of extrahepatic manifestations, but with some limitations. After HCV eradication a good compensation of T2DM has been observed, but doubts persist about the possibility of obtaining a stable reduction in fasting glucose and HbA1c levels.Chronic HCV infection is associated with low total and LDL cholesterol serum levels, which however increase significantly after HCV elimination, possibly due to the disruption of HCV/lipid metabolism interaction. Despite this adverse effect, HCV eradication exerts a favorable action on cardiovascular system, possibly by eliminating numerous other harmful effects exerted by HCV on this system.DAA treatment is also indicated for the treatment of patients with mixed cryoglobulinemia syndrome, since HCV eradication results in symptom reduction and, in particular, is effective in cryoglobulinemic vasculitis. Furthermore, HCV eradication exerts a favorable action on HCV-related lymphoproliferative disorders, with frequent remission or reduction of clinical manifestations.There is also evidence that HCV clearance may improve impaired renal functions, but same conflicting data persist on the effect of some DAAs on eGFR.
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Nevola R, Acierno C, Pafundi PC, Adinolfi LE. Chronic hepatitis C infection induces cardiovascular disease and type 2 diabetes: mechanisms and management. Minerva Med 2020; 112:188-200. [PMID: 33205641 DOI: 10.23736/s0026-4806.20.07129-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Despite the availability of effective treatments, hepatitis C virus (HCV) still remains a threat to public health. HCV is capable to trigger, behind liver damage, extrahepatic manifestations, including cardiovascular disease and type 2 diabetes (T2DM). A close association has been reported between HCV infection and cardiovascular disease due to imbalances in metabolic pathways and chronic inflammation. HCV through both direct and indirect mechanisms causes a higher incidence of ischemic stroke, acute coronary syndrome, heart failure and peripheral arterial disease. In addition, a higher risk of death from cardiovascular events has been showed in HCV patients. Insulin resistance is a hallmark of HCV infection and represents the link between HCV and T2DM, which is one of the most frequent HCV-associated extrahepatic manifestations. The pathological basis of the increased risk of T2DM in HCV infection is provided by the alterations of the molecular mechanisms of IR induced both by the direct effects of the HCV proteins, and by the indirect effects mediated by chronic inflammation, oxidative stress and hepatic steatosis. T2DM increases the risk of compensated and decompensate cirrhosis and hepatocellular carcinoma as well as increases the risk of cardiovascular disease, lower limb amputation and end stage renal disease. Current evidence suggests that HCV eradication reduces the incidence and mortality of cardiovascular disease and T2DM, further underling the importance of public health strategies for eradication the infection. The aim of this review was to update evidence and management of interaction between HCV, cardiovascular disease, and T2DM in the era of DAA treatment.
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Affiliation(s)
- Riccardo Nevola
- Unit of Internal Medicine, Department of Advanced Medical and Surgery Sciences, Luigi Vanvitelli University of Campania, Naples, Italy
| | - Carlo Acierno
- Unit of Internal Medicine, Department of Advanced Medical and Surgery Sciences, Luigi Vanvitelli University of Campania, Naples, Italy
| | - Pia C Pafundi
- Unit of Internal Medicine, Department of Advanced Medical and Surgery Sciences, Luigi Vanvitelli University of Campania, Naples, Italy
| | - Luigi E Adinolfi
- Unit of Internal Medicine, Department of Advanced Medical and Surgery Sciences, Luigi Vanvitelli University of Campania, Naples, Italy -
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Cassano V, Crescibene D, Hribal ML, Pelaia C, Armentaro G, Magurno M, Toscani A, Miceli S, Andreozzi F, Maio R, Perticone M, Sesti G, Perticone F, Sciacqua A. Uric Acid and Vascular Damage in Essential Hypertension: Role of Insulin Resistance. Nutrients 2020; 12:E2509. [PMID: 32825165 PMCID: PMC7551393 DOI: 10.3390/nu12092509] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 08/16/2020] [Accepted: 08/18/2020] [Indexed: 02/07/2023] Open
Abstract
Increased levels of uric acid (UA) have been shown to be correlated with many clinical conditions. Uric acid may adversely affect the insulin signalling pathway inducing insulin resistance (IR). Several studies report the association between arterial stiffness (AS), an early indicator of atherosclerosis, and UA. The purpose of the present study was to evaluate the association between UA and AS, considering the potential role of IR. We enrolled 1114 newly diagnosed, never-treated hypertensive patients. Insulin resistance was assessed by the homeostatic model assessment (HOMA) index. Arterial stiffness was evaluated as the measurement of the carotid-femoral pulse wave velocity (PWV). The study cohort was divided into subgroups, according to increasing tertiles of UA. The mean values of UA were 5.2 ± 1.6 mg/dL in the overall population. Pulse wave velocity was linearly correlated with UA (p < 0.0001), HOMA (p < 0.0001), high sensitivity C-reactive protein (p < 0.0001), systolic blood pressure (p < 0.0001) and LDL cholesterol (p = 0.005). Uric acid was the strongest predictor of PWV and was associated with the highest risk for increased AS. The interaction analysis showed that the joint effect of increased UA and HOMA was significantly higher than that expected in the absence of interaction under the additive model, indicating that the two biomarkers synergically interacted for promoting vascular damage. Our data showed that UA interacted with IR to increase AS in a large cohort of newly diagnosed, never-treated hypertensive patients.
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Affiliation(s)
- Velia Cassano
- Department of Medical and Surgical Sciences; University Magna Græcia of Catanzaro, 88100 Catanzaro, Italy; (V.C.); (D.C.); (M.L.H.); (C.P.); (G.A.); (M.M.); (A.T.); (S.M.); (F.A.); (R.M.); (M.P.); (F.P.)
| | - Daniele Crescibene
- Department of Medical and Surgical Sciences; University Magna Græcia of Catanzaro, 88100 Catanzaro, Italy; (V.C.); (D.C.); (M.L.H.); (C.P.); (G.A.); (M.M.); (A.T.); (S.M.); (F.A.); (R.M.); (M.P.); (F.P.)
| | - Marta Letizia Hribal
- Department of Medical and Surgical Sciences; University Magna Græcia of Catanzaro, 88100 Catanzaro, Italy; (V.C.); (D.C.); (M.L.H.); (C.P.); (G.A.); (M.M.); (A.T.); (S.M.); (F.A.); (R.M.); (M.P.); (F.P.)
| | - Corrado Pelaia
- Department of Medical and Surgical Sciences; University Magna Græcia of Catanzaro, 88100 Catanzaro, Italy; (V.C.); (D.C.); (M.L.H.); (C.P.); (G.A.); (M.M.); (A.T.); (S.M.); (F.A.); (R.M.); (M.P.); (F.P.)
| | - Giuseppe Armentaro
- Department of Medical and Surgical Sciences; University Magna Græcia of Catanzaro, 88100 Catanzaro, Italy; (V.C.); (D.C.); (M.L.H.); (C.P.); (G.A.); (M.M.); (A.T.); (S.M.); (F.A.); (R.M.); (M.P.); (F.P.)
| | - Marcello Magurno
- Department of Medical and Surgical Sciences; University Magna Græcia of Catanzaro, 88100 Catanzaro, Italy; (V.C.); (D.C.); (M.L.H.); (C.P.); (G.A.); (M.M.); (A.T.); (S.M.); (F.A.); (R.M.); (M.P.); (F.P.)
| | - Alfredo Toscani
- Department of Medical and Surgical Sciences; University Magna Græcia of Catanzaro, 88100 Catanzaro, Italy; (V.C.); (D.C.); (M.L.H.); (C.P.); (G.A.); (M.M.); (A.T.); (S.M.); (F.A.); (R.M.); (M.P.); (F.P.)
| | - Sofia Miceli
- Department of Medical and Surgical Sciences; University Magna Græcia of Catanzaro, 88100 Catanzaro, Italy; (V.C.); (D.C.); (M.L.H.); (C.P.); (G.A.); (M.M.); (A.T.); (S.M.); (F.A.); (R.M.); (M.P.); (F.P.)
| | - Francesco Andreozzi
- Department of Medical and Surgical Sciences; University Magna Græcia of Catanzaro, 88100 Catanzaro, Italy; (V.C.); (D.C.); (M.L.H.); (C.P.); (G.A.); (M.M.); (A.T.); (S.M.); (F.A.); (R.M.); (M.P.); (F.P.)
| | - Raffaele Maio
- Department of Medical and Surgical Sciences; University Magna Græcia of Catanzaro, 88100 Catanzaro, Italy; (V.C.); (D.C.); (M.L.H.); (C.P.); (G.A.); (M.M.); (A.T.); (S.M.); (F.A.); (R.M.); (M.P.); (F.P.)
| | - Maria Perticone
- Department of Medical and Surgical Sciences; University Magna Græcia of Catanzaro, 88100 Catanzaro, Italy; (V.C.); (D.C.); (M.L.H.); (C.P.); (G.A.); (M.M.); (A.T.); (S.M.); (F.A.); (R.M.); (M.P.); (F.P.)
| | - Giorgio Sesti
- Department of Clinical and Molecular Medicine, University of Rome-Sapienza, 00161 Rome, Italy;
| | - Francesco Perticone
- Department of Medical and Surgical Sciences; University Magna Græcia of Catanzaro, 88100 Catanzaro, Italy; (V.C.); (D.C.); (M.L.H.); (C.P.); (G.A.); (M.M.); (A.T.); (S.M.); (F.A.); (R.M.); (M.P.); (F.P.)
| | - Angela Sciacqua
- Department of Medical and Surgical Sciences; University Magna Græcia of Catanzaro, 88100 Catanzaro, Italy; (V.C.); (D.C.); (M.L.H.); (C.P.); (G.A.); (M.M.); (A.T.); (S.M.); (F.A.); (R.M.); (M.P.); (F.P.)
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8
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da Silva CB, Vieira DA, de Melo LF, Chagas ALS, Gomes AD, Faria Jr CLLD, Teixeira R, de Magalhães Queiroz DM, Rocha GA, Soares MMS, Bezerra JMT, Silva LD. Interleukin-6-174G/C polymorphism is associated with a decreased risk of type 2 diabetes in patients with chronic hepatitis C virus. World J Hepatol 2020; 12:137-148. [PMID: 32685106 PMCID: PMC7336292 DOI: 10.4254/wjh.v12.i4.137] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Revised: 02/28/2020] [Accepted: 03/22/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Chronic hepatitis C (CHC) is associated with type 2 diabetes mellitus. Although the pathogenesis remains to be elucidated, a growing evidence has suggested a role of pro-inflammatory immune response. Increased serum concentrations of Interleukin 6 (IL-6) have been associated with insulin resistance, type 2 diabetes mellitus as well as advanced forms of liver disease in chronic hepatitis C infection.
AIM To investigate the frequency of IL-6-174G/C (rs1800795) single nucleotide polymorphism (SNP) in CHC patients and in healthy subjects of the same ethnicity. Associations between type 2 diabetes mellitus (dependent variable) and demographic, clinical, nutritional, virological and, IL-6 genotyping data were also investigated in CHC patients.
METHODS Two hundred and forty-five patients with CHC and 179 healthy control subjects (blood donors) were prospectively included. Type 2 diabetes mellitus was diagnosed according to the criteria of the American Diabetes Association. Clinical, biochemical, histological and radiological methods were used for the diagnosis of the liver disease. IL-6 polymorphism was evaluated by Taqman SNP genotyping assay. The data were analysed by logistic regression models.
RESULTS Type 2 diabetes mellitus, blood hypertension and liver cirrhosis were observed in 20.8% (51/245), 40.0% (98/245) and 38.4% (94/245) of the patients, respectively. The frequency of the studied IL-6 SNP did not differ between the CHC patients and controls (P = 0.81) and all alleles were in Hardy-Weinberg equilibrium (P = 0.38). In the multivariate analysis, type 2 diabetes mellitus was inversely associated with GC and CC genotypes of IL-6-174 (OR = 0.42; 95%CI = 0.22-0.78; P = 0.006) and positively associated with blood hypertension (OR = 5.56; 95%CI = 2.79-11.09; P < 0.001).
CONCLUSION This study was the first to show that GC and CC genotypes of IL-6-174 SNP are associated with a decreased risk of type 2 diabetes mellitus in patients chronically infected with hepatitis C virus. The identification of potential inflammatory mediators involved in the crosstalk between hepatitis C virus and the axis pancreas-liver remains important issues that deserve further investigations.
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Affiliation(s)
- Cliviany Borges da Silva
- Sciences Applied to Adult Health Care Post-Graduate Programme, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Diego Alves Vieira
- Medical undergraduate student, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Luisa Freitas de Melo
- Medical undergraduate student, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Anna Luiza Soares Chagas
- Medical undergraduate student, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Adriana Dias Gomes
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - César Lúcio Lopes de Faria Jr
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Rosângela Teixeira
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
- Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Dulciene Maria de Magalhães Queiroz
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Gifone Aguiar Rocha
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Maria Marta Sarquis Soares
- Division of Endocrinology, Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Juliana Maria Trindade Bezerra
- Epidemiology of Infectious and Parasitic Diseases Laboratory, Department of Parasitology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Luciana Diniz Silva
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
- Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
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9
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Sigon G, D'Ambrosio R, Clerici M, Pisano G, Chantarangkul V, Sollazzi R, Lombardi R, Peyvandi F, Lampertico P, Fargion S, Tripodi A, Fracanzani AL. Procoagulant imbalance influences cardiovascular and liver damage in chronic hepatitis C independently of steatosis. Liver Int 2019; 39:2309-2316. [PMID: 31419372 DOI: 10.1111/liv.14213] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2019] [Revised: 07/22/2019] [Accepted: 08/09/2019] [Indexed: 12/16/2022]
Abstract
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.
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Affiliation(s)
- Giordano Sigon
- Unit of Medicine and Metabolic Diseases, Pathophysiology and Transplantation Department, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Roberta D'Ambrosio
- Pathophysiology and Transplantation Department, Gastroenterology and Hepatology, CRC AM e A Migliavacca Center for Liver Diseases, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Mariagrazia Clerici
- IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Milan, Italy
| | - Giuseppina Pisano
- Unit of Medicine and Metabolic Diseases, Pathophysiology and Transplantation Department, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Veena Chantarangkul
- IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Milan, Italy
| | - Roberta Sollazzi
- Unit of Medicine and Metabolic Diseases, Pathophysiology and Transplantation Department, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Rosa Lombardi
- Unit of Medicine and Metabolic Diseases, Pathophysiology and Transplantation Department, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Flora Peyvandi
- Department of Pathophysiology and Transplantation, IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Università degli Studi di Milano, Milan, Italy
| | - Pietro Lampertico
- Pathophysiology and Transplantation Department, Gastroenterology and Hepatology, CRC AM e A Migliavacca Center for Liver Diseases, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Silvia Fargion
- Unit of Medicine and Metabolic Diseases, Pathophysiology and Transplantation Department, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Armando Tripodi
- IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Milan, Italy
| | - Anna Ludovica Fracanzani
- Unit of Medicine and Metabolic Diseases, Pathophysiology and Transplantation Department, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
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10
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Adinolfi LE, Nevola R, Guerrera B, D'Alterio G, Marrone A, Giordano M, Rinaldi L. Hepatitis C virus clearance by direct-acting antiviral treatments and impact on insulin resistance in chronic hepatitis C patients. J Gastroenterol Hepatol 2018; 33:1379-1382. [PMID: 29228501 DOI: 10.1111/jgh.14067] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2017] [Accepted: 12/04/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIM Chronic hepatitis C virus (HCV), particularly genotype 1, is associated with insulin resistance (IR) and diabetes. This study evaluated the impact of HCV clearance by all-oral direct-acting antiviral treatments on IR and glycemic control. METHODS Included in this prospective case-control study were 133 consecutive HCV-genotype 1 patients with advance liver fibrosis (F3-F4) without type 2 diabetes. Sixty eight were treated with direct-acting antiviral and 65 were untreated. Liver fibrosis was assessed by transient elastography. Pre-treatment, end-treatment, and 3 months post-treatment withdrawal IR homeostasis was assessed by homeostatic model assessment (HOMA)-IR, HOMA-S, and HOMA-B. RESULTS At baseline, treated, and untreated patients showed similar liver fibrosis levels, HOMA-IR was 4.90 ± 4.62 and 4.64 ± 5.62, respectively. HOMA-IR correlated with HCV RNA levels. At the end of treatment, all patients cleared HCV RNA, regardless of liver fibrosis and body mass index, and a reduction in HOMA-IR at 2.42 ± 1.85 was showed (P < 0.001); in addition, increased insulin sensitivity, decreased insulin secretion, reduction of serum glucose, and insulin levels were observed. Data were confirmed 3 months after treatment withdrawal in the 65 patients who cleared HCV. No variation occurred in untreated patients. Overall, 76.5% of sustained virologic response patients showed IR improvements, of which 41.2% normalized IR. Improvement of IR was strictly associated with HCV clearance; however, patients with the highest levels of fibrosis remain associated with some degree of IR. CONCLUSIONS The data underline a role of HCV in development of IR and that viral eradication reverses IR and improves glycemic control and this could prevent IR-related clinical manifestations and complications.
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Affiliation(s)
- Luigi E Adinolfi
- Internal Medicine, Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Riccardo Nevola
- Clinical Hospital of Marcianise, ASL Caserta, Caserta, Italy
| | | | - Giovanni D'Alterio
- Internal Medicine, Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Aldo Marrone
- Internal Medicine, Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Mauro Giordano
- Clinical Hospital of Marcianise, ASL Caserta, Caserta, Italy
| | - Luca Rinaldi
- Internal Medicine, Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
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11
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Chou CH, Ho CS, Tsai WC, Wang MC, Tsai YS, Chen JY. Effects of chronic hepatitis C infection on arterial stiffness. ACTA ACUST UNITED AC 2017; 11:716-723. [PMID: 28923555 DOI: 10.1016/j.jash.2017.08.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2017] [Revised: 08/06/2017] [Accepted: 08/18/2017] [Indexed: 02/08/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is associated with increased arterial stiffness. Although chronic hepatitis C virus (HCV) infection was shown to be associated with metabolic disorder and chronic inflammation, the effects of chronic HCV infection on arterial stiffness remain unclear. This study recruited 221 patients including 32 normal controls, 72 NAFLD patients, and 117 subjects with HCV infection. Arterial stiffness was assessed by peripheral arterial stiffness index, Compliance Index (CI), and central arterial stiffness index, Stiffness Index derived from digital volume pulse by photoplethysmography. Levels of oxidative stress marker and inflammatory markers were also measured. The HCV group had significantly lower CI (4.8 ± 3.1 units vs. 3.9 ± 2.1 units vs. 3.0 ± 1.7 units; P for trend <.001) and higher Stiffness Index (7.0 ± 1.6 m/s vs. 8.3 ± 2.3 m/s vs. 8.4 ± 2.3 m/s; P for trend = .001) compared with the normal controls and NAFLD groups. Multivariate linear regression analysis showed that CI was independently correlated with systolic blood pressure (beta = -0.202, P = .013) and HCV infection (beta = -0.216, P = .036). Chronic HCV infection was independently associated with peripheral arterial stiffness. Peripheral arterial stiffness in chronic HCV infection was not associated with a marker of general inflammation (high-sensitivity C-reactive protein); however, a role for more specific markers of inflammation cannot be ruled out.
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Affiliation(s)
- Chang-Hua Chou
- Division of Gastroenterology, Department of Internal Medicine, Tainan Sinlau Hospital, Tainan, Taiwan
| | - Chin-Shan Ho
- Department of Adapted Physical Education, National Taiwan Sport University, Taoyuan, Taiwan
| | - Wei-Chuan Tsai
- Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ming-Cheng Wang
- Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yau-Sheng Tsai
- Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan; Cardiovascular Research Center, National Cheng Kung University, Tainan, Taiwan
| | - Ju-Yi Chen
- Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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12
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The Hypertension of Hemophilia Is Not Explained by the Usual Cardiovascular Risk Factors: Results of a Cohort Study. Int J Hypertens 2016; 2016:2014201. [PMID: 27965893 PMCID: PMC5124662 DOI: 10.1155/2016/2014201] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2016] [Accepted: 10/12/2016] [Indexed: 12/19/2022] Open
Abstract
Background. The etiology of the high prevalence of hypertension among patients with hemophilia (PWH) remains unknown. Methods. We compared 469 PWH in the United States with males from the National Health and Nutrition Examination Survey (NHANES) to determine whether differences in cardiovascular risk factors can account for the hypertension in hemophilia. Results. Median systolic and diastolic BP were higher in PWH than NHANES (P < 0.001) for subjects not taking antihypertensives. Those taking antihypertensives showed similar differences. Differences in both systolic and diastolic BP were especially marked among adults <30 years old. Differences between PWH and NHANES persisted after adjusting for age and risk factors (body mass index, renal function, cholesterol, smoking, diabetes, Hepatitis C, and race). Conclusions. Systolic and diastolic BP are higher in PWH than in the general male population and especially among PWH < 30 years old. The usual cardiovascular risk factors do not account for the etiology of the higher prevalence of hypertension in hemophilia. New investigations into the missing link between hemophilia and hypertension should include age of onset of hypertension and hemophilia-specific morbidities such as the role of inflammatory joint disease.
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13
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Impact of insulin resistance on cardiac and vascular function. Int J Cardiol 2016; 221:1095-9. [DOI: 10.1016/j.ijcard.2016.07.087] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Accepted: 07/04/2016] [Indexed: 12/25/2022]
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14
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Sciacqua A, Perticone M, Tassone EJ, Cimellaro A, Caroleo B, Miceli S, Andreucci M, Licata A, Sesti G, Perticone F. Renal function is impaired in normotensive chronic HCV patients: role of insulin resistance. Intern Emerg Med 2016; 11:553-9. [PMID: 26597876 DOI: 10.1007/s11739-015-1349-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Accepted: 10/28/2015] [Indexed: 12/27/2022]
Abstract
Renal dysfunction is an independent predictor for cardiovascular morbidity and mortality. We investigated whether chronic hepatitis C virus (HCV) infection and the related insulin resistance/hyperinsulinemia influence renal function in comparison with a group of healthy subjects and with another group with metabolic syndrome. We enrolled 130 newly diagnosed HCV outpatients matched for age and gender with 130 patients with metabolic syndrome and 130 healthy subjects. Renal function was evaluated by calculation of glomerular filtration rate (e-GFR, mL/min/1.73 m(2)) using the CKD-EPI equation. The following laboratory parameters were measured: fasting plasma glucose and insulin, total, LDL- and HDL-cholesterol, triglyceride, creatinine, and HOMA to evaluate insulin sensitivity. HCV patients with respect to both healthy subjects and metabolic syndrome patients have a decreased e-GFR: 86.6 ± 16.1 vs 120.2 ± 23.1 mL/min/1.73 m(2) (P < 0.0001) and 94.9 ± 22.6 mL/min/1.73 m(2) (P = 0.003), respectively. Regarding biochemical variables, HCV patients, in comparison with healthy subjects, have a higher triglyceride level, creatinine, fasting insulin and HOMA (3.4 ± 1.4 vs 2.6 ± 1.3; P < 0.0001). At linear regression analysis, the correlation between e-GFR and HOMA is similar in the metabolic syndrome (r = -0.555, P < 0.0001) and HCV (r = -0.527, P < 0.0001) groups. At multiple regression analysis, HOMA is the major determinant of e-GFR in both groups, accounting for, respectively, 30.8 and 27.8 % of its variation in the metabolic syndrome and HCV. In conclusion, we demonstrate that HCV patients have a significant reduction of e-GFR and that insulin resistance is the major predictor of renal dysfunction.
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Affiliation(s)
- Angela Sciacqua
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, V.le Europa, 88100, Catanzaro, Italy
| | - Maria Perticone
- Department of Experimental and Clinical Medicine, University Magna Græcia of Catanzaro, Catanzaro, Italy
| | - Eliezer J Tassone
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, V.le Europa, 88100, Catanzaro, Italy
| | - Antonio Cimellaro
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, V.le Europa, 88100, Catanzaro, Italy
| | - Benedetto Caroleo
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, V.le Europa, 88100, Catanzaro, Italy
| | - Sofia Miceli
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, V.le Europa, 88100, Catanzaro, Italy
| | - Michele Andreucci
- Department of Health Sciences, University Magna Græcia of Catanzaro, Catanzaro, Italy
| | - Anna Licata
- Biomedical Department of Internal and Specialistic Medicine, University of Palermo, Palermo, Italy
| | - Giorgio Sesti
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, V.le Europa, 88100, Catanzaro, Italy
| | - Francesco Perticone
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, V.le Europa, 88100, Catanzaro, Italy.
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15
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Ampuero J, Romero-Gómez M. Assessing cardiovascular risk in hepatitis C: An unmet need. World J Hepatol 2015; 7:2214-2219. [PMID: 26380047 PMCID: PMC4561776 DOI: 10.4254/wjh.v7.i19.2214] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Revised: 04/13/2015] [Accepted: 08/31/2015] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis C virus (HCV) is associated with significant morbidity and mortality, as a result of the progression towards cirrhosis and hepatocellular carcinoma. Additionally, HCV seems to be an independent risk factor for cardiovascular diseases (CVD) due to its association with insulin resistance, diabetes and steatosis. HCV infection represents an initial step in the chronic inflammatory cascade, showing a direct role in altering glucose metabolism. After achieving sustained virological response, the incidence of insulin resistance and diabetes dramatically decrease. HCV core protein plays an essential role in promoting insulin resistance and oxidative stress. On the other hand, atherosclerosis is a common disease in which the artery wall thickens due to accumulation of fatty deposits. The main step in the formation of atherosclerotic plaques is the oxidation of low density lipoprotein particles, together with the increased production of proinflammatory markers [tumor necrosis factor-α, interleukin (IL)-6, IL-18 or C-reactive protein]. The advent of new direct acting antiviral therapy has dramatically increased the sustained virological response rates of hepatitis C infection. In this scenario, the cardiovascular risk has emerged and represents a major concern after the eradication of the virus. Consequently, the number of studies evaluating this association is growing. Data derived from these studies have demonstrated the strong link between HCV infection and the atherogenic process, showing a higher risk of coronary heart disease, carotid atherosclerosis, peripheral artery disease and, ultimately, CVD-related mortality.
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16
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Nagano T, Seki N, Tomita Y, Sugita T, Aida Y, Itagaki M, Sutoh S, Abe H, Tsubota A, Aizawa Y. Impact of Chronic Hepatitis C Virus Genotype 1b Infection on Triglyceride Concentration in Serum Lipoprotein Fractions. Int J Mol Sci 2015; 16:20576-20594. [PMID: 26334270 PMCID: PMC4613219 DOI: 10.3390/ijms160920576] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Revised: 08/13/2015] [Accepted: 08/20/2015] [Indexed: 12/14/2022] Open
Abstract
Reduced low-density lipoprotein (LDL) cholesterol level is a characteristic feature of dyslipidemia in chronic hepatitis C virus (HCV) infection. However, abnormality in serum triglyceride (TG) has not been fully investigated. To clarify the impact of HCV genotype 1b (G1b) infection and advanced fibrosis on serum TG profiles, TG concentrations in lipoprotein fractions were examined in fasting sera from 185 subjects with active or cleared HCV infection by high-performance liquid chromatography. Serum lipoproteins were fractionated into four classes: chylomicron, very low-density lipoprotein (VLDL), LDL, and high-density lipoprotein (HDL). Then, the significance of HCV G1b infection on TG levels in each lipoprotein fraction was determined using multiple regression models. We found that active HCV G1b infection was positively associated with high HDL-TG levels and low VLDL-TG levels, independent of other factors included in the regression model. In VLDL sub-fractions, active HCV infection was only found to be associated with low levels of large VLDL-TG. Similarly, advanced liver fibrosis in chronic HCV G1b infection was associated with high levels of LDL-TG, HDL-TG, and small VLDL-TG, independent of other clinical factors. These findings indicate that active HCV G1b infection and advanced fibrosis are closely associated with abnormal serum TG profiles.
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Affiliation(s)
- Tomohisa Nagano
- Department of Gastroenterology and Hepatology Internal Medicine, Jikei University Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan.
| | - Nobuyoshi Seki
- Department of Gastroenterology and Hepatology Internal Medicine, Jikei University Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan.
| | - Yoichi Tomita
- Department of Gastroenterology and Hepatology Internal Medicine, Jikei University Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan.
| | - Tomonori Sugita
- Department of Gastroenterology and Hepatology Internal Medicine, Jikei University Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan.
| | - Yuta Aida
- Department of Gastroenterology and Hepatology Internal Medicine, Jikei University Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan.
| | - Munenori Itagaki
- Department of Gastroenterology and Hepatology Internal Medicine, Jikei University Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan.
| | - Satoshi Sutoh
- Department of Gastroenterology and Hepatology Internal Medicine, Jikei University Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan.
| | - Hiroshi Abe
- Department of Gastroenterology and Hepatology Internal Medicine, Jikei University Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan.
| | - Akihito Tsubota
- Core Research Facilities for Basic Science, Research Center for Medical Science, Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan.
| | - Yoshio Aizawa
- Department of Gastroenterology and Hepatology Internal Medicine, Jikei University Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan.
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Sciacqua A, Perticone M, Cimellaro A, Tassone EJ, Tripepi G, Andreucci M, Sesti G, Perticone F. Multiplicative effect of serum phosphorus levels and insulin resistance on hypertensive vascular stiffness. Thromb Haemost 2015; 115:227-9. [PMID: 26290443 DOI: 10.1160/th15-04-0349] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Accepted: 07/03/2015] [Indexed: 11/05/2022]
Affiliation(s)
| | | | | | | | | | | | | | - Francesco Perticone
- Francesco Perticone, MD, Department of Medical and Surgical Sciences, Campus Universitario di Germaneto, V.le Europa, 88100 - Catanzaro, Italy, Tel.: +39 0961 3647149, Fax: +39 0961 3647634, E-mail:
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