|
1
|
Horbal SR, Belancourt PX, Zhang P, Holcombe SA, Saini S, Wang SC, Sales AE, Su GL. Independent Associations of Aortic Calcification with Cirrhosis and Liver Related Mortality in Veterans with Chronic Liver Disease. Dig Dis Sci 2024; 69:2681-2690. [PMID: 38653948 PMCID: PMC11258161 DOI: 10.1007/s10620-024-08450-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Accepted: 04/12/2024] [Indexed: 04/25/2024]
Abstract
INTRODUCTION Abdominal aortic calcifications (AAC) are incidentally found on medical imaging and useful cardiovascular burden approximations. The Morphomic Aortic Calcification Score (MAC) leverages automated deep learning methods to quantify and score AACs. While associations of AAC and non-alcoholic fatty liver disease (NAFLD) have been described, relationships of AAC with other liver diseases and clinical outcome are sparse. This study's purpose was to evaluate AAC and liver-related death in a cohort of Veterans with chronic liver disease (CLD). METHODS We utilized the VISN 10 CLD cohort, a regional cohort of Veterans with the three forms of CLD: NAFLD, hepatitis C (HCV), alcohol-associated (ETOH), seen between 2008 and 2014, with abdominal CT scans (n = 3604). Associations between MAC and cirrhosis development, liver decompensation, liver-related death, and overall death were evaluated with Cox proportional hazard models. RESULTS The full cohort demonstrated strong associations of MAC and cirrhosis after adjustment: HR 2.13 (95% CI 1.63, 2.78), decompensation HR 2.19 (95% CI 1.60, 3.02), liver-related death HR 2.13 (95% CI 1.46, 3.11), and overall death HR 1.47 (95% CI 1.27, 1.71). These associations seemed to be driven by the non-NAFLD groups for decompensation and liver-related death [HR 2.80 (95% CI 1.52, 5.17; HR 2.34 (95% CI 1.14, 4.83), respectively]. DISCUSSION MAC was strongly and independently associated with cirrhosis, liver decompensation, liver-related death, and overall death. Surprisingly, stratification results demonstrated comparable or stronger associations among those with non-NAFLD etiology. These findings suggest abdominal aortic calcification may predict liver disease severity and clinical outcomes in patients with CLD.
Collapse
Affiliation(s)
- Steven R Horbal
- Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
- Morphomics Analysis Group, University of Michigan, Ann Arbor, MI, USA.
| | | | - Peng Zhang
- Department of Surgery, University of Michigan, Ann Arbor, MI, USA
- Morphomics Analysis Group, University of Michigan, Ann Arbor, MI, USA
| | - Sven A Holcombe
- Department of Surgery, University of Michigan, Ann Arbor, MI, USA
- Morphomics Analysis Group, University of Michigan, Ann Arbor, MI, USA
| | - Sameer Saini
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
| | - Stewart C Wang
- Department of Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Anne E Sales
- VA Ann Arbor Healthcare System, Ann Arbor, MI, USA
- Sinclair School of Nursing and Department of Family and Community Medicine, University of Missouri, Colombia, MO, USA
| | - Grace L Su
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
- Gastroenterology Section, Ann Arbor VA Healthcare System, Ann Arbor, MI, USA
| |
Collapse
|
|
2
|
Zhang M, Han Z, Lin Y, Jin Z, Zhou S, Wang S, Tang Y, Li J, Li X, Chen H. Understanding the relationship between HCV infection and progression of kidney disease. Front Microbiol 2024; 15:1418301. [PMID: 39006752 PMCID: PMC11239345 DOI: 10.3389/fmicb.2024.1418301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 06/18/2024] [Indexed: 07/16/2024] Open
Abstract
Hepatitis C virus (HCV) can cause a range of kidney diseases. HCV is the primary cause of mixed cryoglobulinaemia, which leads to cryoglobulinaemic vasculitis and cryoglobulinaemic glomerulonephritis (GN). Patients with acute cryoglobulinaemic vasculitis often exhibit acute kidney disease due to HCV infection, which typically progresses to acute kidney injury (AKI). HCV also increases the risk of chronic kidney disease (CKD) and the likelihood of developing end-stage renal disease (ESRD). Currently, direct-acting antiviral agents (DAAs) can be used to treat kidney disease at different stages. This review focuses on key findings regarding HCV and kidney disease, discusses the impact of DAAs, and highlights the need for further research and treatment.
Collapse
Affiliation(s)
- Meiqi Zhang
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Zhongyu Han
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Naniing Tongren Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Yumeng Lin
- Naniing Tongren Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Zi Jin
- Department of Anesthesiology and Pain Rehabilitation, Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, China
| | - Shuwei Zhou
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Siyu Wang
- Department of Gastroenterology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Yuping Tang
- Hepatobiliary Department of the Third Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Nanning, Guangxi, China
| | - Jiaxuan Li
- School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
| | - Xueping Li
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Haoran Chen
- Department of General Surgery, Chengdu Xinhua Hospital Affiliated to North Sichuan Medical College, Chengdu, China
| |
Collapse
|
|
3
|
Hepatitis C Virus-Lipid Interplay: Pathogenesis and Clinical Impact. Biomedicines 2023; 11:biomedicines11020271. [PMID: 36830808 PMCID: PMC9953247 DOI: 10.3390/biomedicines11020271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 01/13/2023] [Accepted: 01/16/2023] [Indexed: 01/20/2023] Open
Abstract
Hepatitis C virus (HCV) infection represents the major cause of chronic liver disease, leading to a wide range of hepatic diseases, including cirrhosis and hepatocellular carcinoma. It is the leading indication for liver transplantation worldwide. In addition, there is a growing body of evidence concerning the role of HCV in extrahepatic manifestations, including immune-related disorders and metabolic abnormalities, such as insulin resistance and steatosis. HCV depends on its host cells to propagate successfully, and every aspect of the HCV life cycle is closely related to human lipid metabolism. The virus circulates as a lipid-rich particle, entering the hepatocyte via lipoprotein cell receptors. It has also been shown to upregulate lipid biosynthesis and impair lipid degradation, resulting in significant intracellular lipid accumulation (steatosis) and circulating hypocholesterolemia. Patients with chronic HCV are at increased risk for hepatic steatosis, dyslipidemia, and cardiovascular disease, including accelerated atherosclerosis. This review aims to describe different aspects of the HCV viral life cycle as it impacts host lipoproteins and lipid metabolism. It then discusses the mechanisms of HCV-related hepatic steatosis, hypocholesterolemia, and accelerated atherosclerosis.
Collapse
|
|
4
|
Kennedy M, Roche S, McGowan M, Singleton E, Elsheikh E, O'Donovan M, Ryan K, O'Connell NM, O'Mahony B, Lavin M, O'Donnell JS, Turecek PL, Gormley J. Physical activity, physical fitness and cardiometabolic risk amongst adults with moderate and severe haemophilia. Haemophilia 2023; 29:72-83. [PMID: 36195106 PMCID: PMC10092720 DOI: 10.1111/hae.14653] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 07/28/2022] [Accepted: 08/18/2022] [Indexed: 01/25/2023]
Abstract
AIM This study aimed to examine physical activity (PA), physical fitness and cardiometabolic risk amongst people with moderate and severe haemophilia (PwMSH). METHODS The following domains were examined: PA (accelerometry); functional aerobic capacity (6-Minute Walk Test); grip strength (dynamometry); balance (One Leg Stand Test); body composition (anthropometry and bioimpedance analysis); blood pressure; arterial stiffness; and cardiometabolic disorders. RESULTS A total of 53 PwMSH (44 years) and 33 controls (43 years; p = .679) were recruited. Compared to controls, PwMSH were significantly less active in moderate and vigorous PA parameters (all p < .05), and less physically fit indicated by 6-Minute Walk distance (p < .0005), grip strength (p = .040) and balance (p < .0005). PwMSH had higher rates of abdominal adiposity compared to controls measured by waist circumference indices (all p < .05). Resting blood pressure and arterial stiffness were not significantly different (p = .797 and .818, respectively). With respect to overall PA, World Health Organisation recommended targets for adults were achieved by the majority of both groups (haemophilia: 72.9% vs. controls: 90.0%; p = .069). Importantly, the number of PwMSH who achieved guideline recommended PA via longer, sustained bouts of moderate-vigorous PA was significantly lower compared to controls (18.8% vs. 56.7%; p = .001). Lastly, clinically diagnosed hypertension, insulin resistance and hyperlipidaemia were more prevalent amongst PwMSH compared to controls. CONCLUSION Low levels of PA and physical fitness, and significant rates of abdominal adiposity and hypertension may collectively influence the risk and severity of various cardiometabolic and/or musculoskeletal health issues amongst ageing PwMSH. Personalised multi-disciplinary health interventions involving PA, dietary and health psychology input for PwMSH warrant future investigation.
Collapse
Affiliation(s)
- Megan Kennedy
- Discipline of Physiotherapy, Trinity Centre for Health Sciences, Trinity College Dublin, St. James's Hospital, Dublin, Ireland
| | - Sheila Roche
- National Coagulation Centre, St. James's Hospital, Dublin, Ireland
| | - Mark McGowan
- National Coagulation Centre, St. James's Hospital, Dublin, Ireland
| | - Evelyn Singleton
- National Coagulation Centre, St. James's Hospital, Dublin, Ireland
| | - Einas Elsheikh
- National Coagulation Centre, St. James's Hospital, Dublin, Ireland.,Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland
| | | | - Kevin Ryan
- National Coagulation Centre, St. James's Hospital, Dublin, Ireland
| | | | | | - Michelle Lavin
- National Coagulation Centre, St. James's Hospital, Dublin, Ireland.,Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - James S O'Donnell
- National Coagulation Centre, St. James's Hospital, Dublin, Ireland.,Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Peter L Turecek
- Baxalta Innovations GmbH, A Member of the Takeda Group of Companies, Vienna, Austria
| | - John Gormley
- Discipline of Physiotherapy, Trinity Centre for Health Sciences, Trinity College Dublin, St. James's Hospital, Dublin, Ireland
| | | |
Collapse
|
|
5
|
Habas E, Farfar KL, Errayes N, Habas AM, Errayes M, Alfitori G, Rayani A, Elgara M, Al Adab AH, Elzouki A. Hepatitis Virus C-associated Nephropathy: A Review and Update. Cureus 2022; 14:e27322. [PMID: 36043014 PMCID: PMC9412079 DOI: 10.7759/cureus.27322] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/26/2022] [Indexed: 11/17/2022] Open
Abstract
Hepatitis C virus (HCV) infection causes hepatic and extrahepatic organ involvement. Chronic kidney disease (CKD) is a prevalent non-communicable disorder, accounting for significant morbidity and mortality worldwide. Acute kidney injury and CKD are not uncommon sequels of acute or chronic HCV infection. The pathogenesis of HCV-associated kidney injuries is not well explored. Excess cryoglobulin production occurs in HCV infection. The cryoglobulin may initiate immune complex-mediated vasculitis, inducing vascular thrombosis and inflammation due to cryoglobulin deposits. Furthermore, direct damage to nephron parts also occurs in HCV patients. Other contributory causes such as hypertension, diabetes, and genetic polymorphism enhance the risk of kidney damage in HCV-infected individuals. Implementing CKD prevention, regular evaluation, and therapy may improve the HCV burden of kidney damage and its related outcomes. Therefore, in this review, we discuss and update the possible mechanism(s) of kidney injury pathogenesis with HCV infection. We searched for related published articles in EMBASE, Google Scholar, Google, PubMed, and Scopus. We used various texts and phrases, including hepatitis virus and kidney, HCV and CKD, kidney pathology in viral hepatitis, kidney transplantation in HCV-infected patients, kidney allograft survival in viral hepatitis patients, mechanism of kidney pathology in viral hepatitis, dialysis and viral hepatitis, HCV infection and kidney injuries, and viral hepatitis and CKD progression, etc. to identify relevant articles.
Collapse
|
|
6
|
Broker M, Frager SZ, Patel NS, Lebovics E, Frishman WH. The Inflammatory Relationship Between Hepatitis C Virus With Coronary and Carotid Atherosclerosis. Cardiol Rev 2021; 29:178-183. [PMID: 32618587 DOI: 10.1097/crd.0000000000000314] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Hepatitis C virus (HCV), a global health concern, has been linked to various hepatic and extrahepatic deleterious manifestations. Several observational studies have either supported the increased likelihood of coronary and carotid atherosclerosis after infection with HCV or refuted it. To date, there has been no clear consensus to support either train of thought, as randomized, controlled clinical trials have not been completed. In this review, we first discuss articles that support the notion that HCV infection leads to increased plaque formation due to systemic inflammation and then focus on articles that refute this idea. From the literature, we do know that both inflammatory and lipid processes play a role in plaque formation, and thus both components are important in the successful treatment of atherosclerosis. Based on our review of the literature, we do believe that HCV-infected individuals are at an increased risk for more severe coronary artery disease than their healthy counterparts. Although there is no irrefutable evidence that links HCV infection with plaque formation and/or rupture, cardioprotective measures should be taken to reduce poor health outcomes, especially in those individuals who are already at risk of coronary disease.
Collapse
Affiliation(s)
- Michael Broker
- From the Department of Medicine, New York Medical College/Westchester Medical Center, Valhalla, NY
| | - Shalom Z Frager
- Department of Medicine, Division of Gastroenterology and Hepatology, New York Medical College/Westchester Medical Center, Valhalla, NY
| | - Nayan S Patel
- Department of Medicine, University of Rochester/Strong Memorial Hospital, Rochester, NY
| | - Edward Lebovics
- Department of Medicine, Division of Gastroenterology and Hepatology, New York Medical College/Westchester Medical Center, Valhalla, NY
| | - William H Frishman
- From the Department of Medicine, New York Medical College/Westchester Medical Center, Valhalla, NY
| |
Collapse
|
|
7
|
Haykal M, Matsumori A, Saleh A, Fayez M, Negm H, Shalaby M, Bassuony S. Diagnosis and treatment of HCV heart diseases. Expert Rev Cardiovasc Ther 2021; 19:493-499. [PMID: 33861939 DOI: 10.1080/14779072.2021.1917383] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Hepatitis C virus (HCV) infection is an important cause of a variety of otherwise unexplained heart diseases and myocardial injury. A high prevalence of HCV infection has been noted in patients with hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular dysplasia/cardiomyopathy and myocarditis. Various arrhythmias, conduction disturbances and QT prolongation were also associated with HCV infection. A possible role of HCV infection in the pathogenesis of diabetes and atherosclerosis, and the role of immunogenetics of HCV cardiomyopathies is discussed. Recent studies suggest that mononuclear cells may be the major target of HCV, and clinical applications to test this new hypothesis are discussed. AREAS COVERED In this review, we will evaluate the evidence that HCV causes various cardiovascular diseases, and discuss on the pathogenesis of these disorders. EXPERT OPINION HCV is the cause of many different forms of heart disease worldwide, but their existence has not been recognized by most of cardiologists. The recognition and diagnosis are indispensable for the early treatment of these diseases. The diverse clinical manifestation of HCV infection and the presence of multiple extrahepatic disease syndromes could be explained by a new hypothesis that the target of HCV is leukocytes.
Collapse
Affiliation(s)
- Mohammad Haykal
- Cardiovascular and Ultrasonography Research Unit (CURU), Research Institute of Ophthalmology (RIO), Cairo, Egypt
| | - Akira Matsumori
- Clinical Research Center, Kyoto Medical Center, Kyoto, Japan
| | - Ahmed Saleh
- Cardiovascular and Ultrasonography Research Unit (CURU), Research Institute of Ophthalmology (RIO), Cairo, Egypt
| | - Moatez Fayez
- Cardiovascular and Ultrasonography Research Unit (CURU), Research Institute of Ophthalmology (RIO), Cairo, Egypt
| | - Hany Negm
- Cardiovascular and Ultrasonography Research Unit (CURU), Research Institute of Ophthalmology (RIO), Cairo, Egypt
| | - Mohammad Shalaby
- Cardiovascular and Ultrasonography Research Unit (CURU), Research Institute of Ophthalmology (RIO), Cairo, Egypt
| | - Samar Bassuony
- Cardiovascular and Ultrasonography Research Unit (CURU), Research Institute of Ophthalmology (RIO), Cairo, Egypt
| |
Collapse
|
|
8
|
Pennisi G, Spatola F, DI Marco L, DI Martino V, DI Marco V. Impact of Direct-Acting Antivirals (daas) on cardiovascular diseases in patients with chronic hepatitis C. Minerva Gastroenterol (Torino) 2021; 67:254-263. [PMID: 33971709 DOI: 10.23736/s2724-5985.21.02875-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
In the last years the hepatitis C virus (HCV) infection was a relevant public health problem due to the large number of affected people worldwide and the impact on hepatic and extrahepatic complications. The availability of direct-acting antivirals (DAAs) and the very high rate of sustained virological response (SVR) after treatment has radically changed the course of HCV chronic infection. Robust evidence showed a close link between HCV infection and development of cardiovascular disease (CVD), as result of the atherogenic effect of the virus. This review aims to explore the evidence linking HCV infection with cardiovascular disease and to evaluate the impact of SVR after DAAs on cardiovascular complications.
Collapse
Affiliation(s)
- Grazia Pennisi
- Section of Gastroenterology and Hepatology, Dipartimento Di Promozione Della Salute, Materno Infantile, Medicina Interna e Specialistica Di Eccellenza (PROMISE), University of Palermo, Palermo, Italy -
| | - Federica Spatola
- Section of Gastroenterology and Hepatology, Dipartimento Di Promozione Della Salute, Materno Infantile, Medicina Interna e Specialistica Di Eccellenza (PROMISE), University of Palermo, Palermo, Italy
| | - Lorenza DI Marco
- Gastroenterology Unit, Department of Medical Specialties, University of Modena & Reggio Emilia, Modena, Italy
| | - Vincenzo DI Martino
- Section of Gastroenterology and Hepatology, Dipartimento Di Promozione Della Salute, Materno Infantile, Medicina Interna e Specialistica Di Eccellenza (PROMISE), University of Palermo, Palermo, Italy
| | - Vito DI Marco
- Section of Gastroenterology and Hepatology, Dipartimento Di Promozione Della Salute, Materno Infantile, Medicina Interna e Specialistica Di Eccellenza (PROMISE), University of Palermo, Palermo, Italy
| |
Collapse
|
|
9
|
Shengir M, Elgara M, Sebastiani G. Metabolic and cardiovascular complications after virological cure in hepatitis C: What awaits beyond. World J Gastroenterol 2021; 27:1959-1972. [PMID: 34007133 PMCID: PMC8108037 DOI: 10.3748/wjg.v27.i17.1959] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 03/06/2021] [Accepted: 04/12/2021] [Indexed: 02/06/2023] Open
Abstract
The association between chronic hepatitis C (CHC) infection and extrahepatic manifestations (EHMs), particularly cardiometabolic diseases, has been extensively examined. However, there has still been insufficient evaluation for these EHMs after virological cure. Several multidirectional mechanisms have been proposed explaining the ability of hepatitis C virus (HCV) developing EHMs, cardiometabolic ones, as well as the effect of antiviral therapy to resolve these EHMs. Data on these manifestations after achieving sustained virologic response (SVR) are still conflicting. However, current evidence suggests that reversal of hepatic steatosis and its coexistent hypocholesterolemia after successful viral eradication led to unfavorable lipid profile, which increases cardiovascular disease (CVD) risk. Additionally, most observations showed that metabolic alterations, such as insulin resistance and diabetes mellitus (DM), undergo some degree of reduction after viral clearance. These changes seem HCV-genotype dependent. Interferon-based antiviral therapy and direct acting antiviral drugs were shown to minimize incidence of DM. Large epidemiological studies that investigated the effect of SVR on CVD showed great discrepancies in terms of results, with predominant findings indicating that CVD events decreased in patients with SVR compared to non-responders or untreated ones. In this review, we present a summary of the current knowledge regarding extrahepatic sequelae of CHC following SVR, which may have an impact on healthcare providers’ clinical practice.
Collapse
Affiliation(s)
- Mohamed Shengir
- Department of Medicine, McGill University, Montreal, Quebec H3A0G4, Canada
| | - Mohamed Elgara
- Department of Internal Medicine, Hamad Medical Corporation, Doha 3050, Qatar
| | - Giada Sebastiani
- Department of Medicine, McGill University Health Center, Montreal, Quebec H4A3J1, Canada
| |
Collapse
|
|
10
|
Bailey AL, Al-Adwan S, Sneij E, Campbell N, Wiisanen ME. Atherosclerotic Cardiovascular Disease in Individuals with Hepatitis C Viral Infection. Curr Cardiol Rep 2021; 23:52. [PMID: 33822282 DOI: 10.1007/s11886-021-01475-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/11/2021] [Indexed: 12/09/2022]
Abstract
PURPOSE OF REVIEW Hepatitis C virus (HCV) and atherosclerotic cardiovascular disease (ASCVD) are two diseases that affect millions around the globe. Hepatitis C affects more than 70 million individuals globally. ASCVD is commonly encountered and remains the top cause of death worldwide. A link has been identified between HCV and atherosclerosis. RECENT FINDINGS A review of recent studies which define the association between HCV infection and an increased risk of subclinical ASCVD and experiencing cardiovascular (CV) events. It is now recognized that there is an increased burden of atherosclerosis in individuals infected with HCV that translates into increased cardiovascular events. An increase in the number of diagnosed cases of HCV is expected as screening recommendations for the virus have expanded. Strategies to educate healthcare professionals about this increased CV risk will need to be considered as well as the optimal strategy to lower CV risk in this growing population.
Collapse
Affiliation(s)
- Alison L Bailey
- Centennial Heart at Parkridge, HCA Healthcare, 2205 McCallie Avenue, Chattanooga, TN, 37404, USA.
| | - Saif Al-Adwan
- Department of Medicine, Erlanger Heart and Lung Institute/University of Tennessee College of Medicine Chattanooga, Chattanooga, TN, USA
| | - Eliea Sneij
- Department of Medicine, University of Tennessee College of Medicine Chattanooga, Chattanooga, TN, USA
| | - Nicholas Campbell
- Department of Medicine, University of Tennessee College of Medicine Chattanooga, Chattanooga, TN, USA
| | - Matthew E Wiisanen
- Centennial Heart at Parkridge, HCA Healthcare, 2205 McCallie Avenue, Chattanooga, TN, 37404, USA
| |
Collapse
|
|
11
|
Hsu WT, Yang DH, Liao CC, Chen JW, Hsu WH, Kuo CW, Hsu HC, Chang SH, Chen LM. Blood Glucose and Renal Function Evaluation in Patients with Viral Hepatitis. Diabetes Metab Syndr Obes 2021; 14:3337-3344. [PMID: 34321900 PMCID: PMC8312512 DOI: 10.2147/dmso.s303252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Accepted: 05/10/2021] [Indexed: 11/26/2022] Open
Abstract
PURPOSE To evaluate the blood glucose and renal function, determine the prevalence of hyperglycemia/diabetes mellitus (DM) and renal disease (nephropathy), and investigate the association between hyperglycemia/DM and renal disease in patients with viral hepatitis (VH). PATIENTS AND METHODS A total of 491 subjects were included in the study. Patients with VH were further divided into the hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, and HBV-HCV co-infection subgroups. Fasting blood glucose, glycated hemoglobin (HbA1c), glycated albumin (GA), glutamic oxaloacetic transaminase (GOT), creatinine (Cr), and cystatin C (Cys C) levels were measured. Urine microalbumin levels were also assessed. Formulas for estimated average glucose calculated using glycated albumin(eAG(GA)), estimated average glucose calculated using HbA1c (eAG(HbA1c)), and estimated glomerular filtration rate calculated using cystatin C (eGFRcys) were used to evaluate the average glucose and renal function. RESULTS The prevalence of hyperglycemia/DM and renal disease was significantly higher in the VH group, especially in the HCV subgroup. The prevalence of renal disease was significantly higher in patients with VH with eAG(GA) ≥200 mg/dL. CONCLUSION Our study used multiple parameters to evaluate blood glucose and renal function in patients with VH and found that hyperglycemia/DM and renal disease are closely associated with VH, especially in subjects with HCV infection. Patients with VH, especially those with HCV infection and hyperglycemia/DM, were particularly vulnerable to renal disease.
Collapse
Affiliation(s)
- Wen-Tung Hsu
- Division of Laboratory, Taichung Armed Force General Hospital, Taichung, Taiwan, Republic of China
| | - Deng-Ho Yang
- Division of Laboratory, Taichung Armed Force General Hospital, Taichung, Taiwan, Republic of China
- Department of Internal Medicine, Taichung Armed Force General Hospital, Taichung, Taiwan, Republic of China
- School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
- Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan, Republic of China
| | - Chun-Cheng Liao
- School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
- Department of Family Medicine, Taichung Armed Force General Hospital, Taichung, Taiwan, Republic of China
| | - Jia -Wen Chen
- Medicine Laboratory, Ministry of Health and Welfare Feng Yuan Hospital, Taichung, Taiwan, Republic of China
| | - Wen-Hsiu Hsu
- School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
- Division of Gastroenterology, Taichung Armed Force General Hospital, Taichung, Taiwan, Republic of China
| | - Chia-Wen Kuo
- School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
- Division of Nephrology, Taichung Armed Force General Hospital, Taichung, Taiwan, Republic of China
| | - Hung-Chang Hsu
- Division of Laboratory, Ching Chyuan Hospital, Taichung, Taiwan, Republic of China
| | - Sheng-Huang Chang
- Tsaotun Psychiatric Center, Ministry of Health and Welfare, Nantou, Taiwan, Republic of China
| | - Li-Mien Chen
- Department of Internal Medicine, Taichung Armed Force General Hospital, Taichung, Taiwan, Republic of China
- School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
- Correspondence: Li-Mien Chen Department of Internal Medicine, Taichung Armed Force General Hospital, No. 348, Sec. 2, Chung-Shan Road, Taiping, Taichung, Taiwan, Republic of China Email
| |
Collapse
|
|
12
|
Hussein A, Abdel Ghany M, Mahmoud HEM. Short- and long-term outcomes following percutaneous coronary intervention in hepatitis C virus seropositive patients. Egypt Heart J 2020; 72:44. [PMID: 32712829 PMCID: PMC7382666 DOI: 10.1186/s43044-020-00079-9] [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: 05/15/2020] [Accepted: 07/09/2020] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Hepatitis C virus (HCV) infection is progressively recognized as a potential atherogenic condition that is associated with coronary artery disease (CAD). Factors that affect the cardiovascular system as diabetes mellitus and dyslipidemia also may affect the outcomes following PCI. So, HCV infection may have an impact on the outcomes following PCI. We aimed to investigate the impact of HCV seropositivity on the outcomes following percutaneous coronary intervention (PCI).
Results
We conducted a multi-center prospective cohort study on 400 patients candidate for elective PCI using drug-eluting stents; 200 patients were HCV seropositive and did not received antiviral treatment, and 200 patients were HCV seronegative. The patients were followed up for 1 year for the development of major adverse cardiovascular events (MACEs) and clinical in-stent restenosis. Multivariate Cox hazard regression analyses for MACEs and clinical in-stent restenosis at 12 months after adjustment for confounding factors showed that HCV seropositivity did not present a higher hazard upon MACEs (adjusted hazard ratio (HR) 0.74; 95% CI 0.41–1.32; p value 0.302), the individual cardiovascular outcomes (target lesion revascularization (TLR), target vessel revascularization (TVR), myocardial infarction (MI), cerebrovascular stroke (CVS), stent thrombosis, major bleeding, coronary artery bypass graft (CABG), cardiac death, and non-cardiac death), or the incidence of clinical in-stent restenosis (adjusted HR was 1.70; 95% CI 0.64–4.51; p value 0.28) compared to seronegative patients.
Conclusion
HCV seropositivity had no impact on MACEs, individual cardiovascular outcomes, or clinical in-stent restenosis following PCI for a 1 year follow-up period.
Collapse
|
|
13
|
Effects of Eradication of HCV on Cardiovascular Risk and Preclinical Atherosclerosis in HIV/HCV-Coinfected Patients. J Acquir Immune Defic Syndr 2020; 83:292-300. [PMID: 31913996 DOI: 10.1097/qai.0000000000002260] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND To assess the effects of eradication of hepatitis C virus (HCV) on cardiovascular risk (CVR) and preclinical atherosclerosis in HIV/HCV-coinfected patients. SETTING Prospective cohort study. METHODS We assessed serum lipids, 10-year Framingham CVR scores, pulse wave velocity, carotid intima-media thickness, and biomarkers of inflammation and endothelial dysfunction (BMKs) at baseline and 96 weeks (wk) after initiation of anti-HCV therapy (Rx) in HIV/HCV-coinfected patients. RESULTS A total of 237 patients were included. Anti-HCV therapy comprised pegylated interferon and ribavirin plus 1 direct-acting antiviral in 55.2%, pegylated interferon and ribavirin in 33.8%, and all-oral direct-acting antiviral in 11.0%. A total of 147 (62.0%) patients achieved sustained viral response (SVR). Median increases in low-density lipoprotein cholesterol in patients with and without SVR were 14 mg/dL and 0 mg/dL (P = 0.024), respectively. Increases in CVR categories were found in 26.9% of patients with SVR (P = 0.005 vs. baseline) and 8.1% of patients without SVR (P = 0.433). This resulted in a significant interaction between SVR and CVR over time (P < 0.001). No significant effect of SVR was observed for pulse wave velocity (P = 0.446), carotid intima-media thickness (P = 0.320), and BMKs of inflammation and endothelial dysfunction. CONCLUSIONS In coinfected patients, eradication of HCV had no effect on markers of preclinical atherosclerosis and BMKs of inflammation and endothelial dysfunction but was associated with a clinically relevant rise in serum low-density lipoprotein cholesterol. Evaluation of CVR should be an integral part of care after the cure of chronic hepatitis C in patients with HIV.
Collapse
|
|
14
|
Abstract
INTRODUCTION Hepatitis C virus (HCV) infection is associated with an increased incidence and progression of chronic kidney disease (CKD), as well as higher mortality in CKD and renal transplant patients. Direct acting antiviral agents (DAAs) have revolutionized the treatment of HCV, with viral eradication attained in 90-100% of treated patients. DAAs have an excellent safety and tolerability profile in CKD and renal transplant patients. AREAS COVERED In this review, we discuss the association of HCV with incidence and progression of CKD as well as its effect on outcomes and mortality. We also discuss the available treatment options in patients with CKD and renal transplant and in HCV-associated glomerular disease. EXPERT OPINION The availability of newly available direct acting anti-viral agents has revolutionized the treatment of HCV in persons with advanced CKD and undergoing dialysis. With these regimens, viral eradication can be attained in 90-100% of the treated patients. The safety, tolerability, and efficacy of these drugs in renal transplant patients have also made it possible to use HCV-infected grafts and successful virus eradication at a later stage.
Collapse
Affiliation(s)
- Muhammad Umair Khan
- Department of Medicine, Division of Gastroenterology, Hamad Medical Corporation , Doha, Qatar
| | - Mohamed Ibrahim Mahmoud
- Department of Medicine, Division of Gastroenterology, Hamad Medical Corporation , Doha, Qatar
| | - Adeel A Butt
- Weill Cornell Medical College , New York, Qatar.,Department of Medicine, Hamad Medical Corporation , Doha, Qatar
| |
Collapse
|
|
15
|
Chen Y, Ji H, Shao J, Jia Y, Bao Q, Zhu J, Zhang L, Shen Y. Different Hepatitis C Virus Infection Statuses Show a Significant Risk of Developing Type 2 Diabetes Mellitus: A Network Meta-Analysis. Dig Dis Sci 2020; 65:1940-1950. [PMID: 31758432 DOI: 10.1007/s10620-019-05918-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Accepted: 10/22/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND The role of hepatitis C virus (HCV) infection statuses in the development of type 2 diabetes mellitus (T2DM) has not been completely understood. AIM To evaluate the prevalence of T2DM in patients with different HCV infection statuses. METHODS We conducted a systematic study on T2DM risk in five types of individuals with different HCV infection statuses: non-HCV controls, HCV-cleared patients, chronic HCV patients without cirrhosis, patients with HCV cirrhosis and patients with decompensated HCV cirrhosis. Studies published from 2010 to 2019 were selected. Both pairwise and network meta-analyses were employed to compare the T2DM risk among patients with different HCV infection statuses. RESULTS The pairwise meta-analysis showed that non-HCV (OR = 0.60, 95% CI [0.47-0.78]) had a lower risk of T2DM compared with CHC, while cirrhosis had a significant higher risk (OR = 1.90, 95% CI [1.60-2.26]). Network meta-analysis further demonstrated patients with HCV infection were at a significantly higher risk of T2DM than those without HCV infection or with HCV clearance, while decompensated cirrhosis had a significant higher T2DM risk than non-HCV (OR = 3.84, 95% CI [2.01-7.34]), patients with HCV clearance (OR = 3.17, 95% CI [1.49-6.73]), and CHC patients (OR = 2.21, 95% CI [1.24-3.94]). CONCLUSIONS HCV infection is a significant risk factor for developing T2DM. CHC, cirrhosis, and decompensated cirrhosis contribute to an increasingly greater risk of T2DM, but HCV clearance spontaneously or through clinical treatment may immediately reduce the risk of the onset and development of T2DM.
Collapse
Affiliation(s)
- Ying Chen
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, 9 Se-Yuan Road, Nantong, 226019, Jiangsu, China
| | - Hanzhen Ji
- Centre for Liver Diseases, Nantong Third People's Hospital, Nantong University, Nantong, China
| | - Jianguo Shao
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, 9 Se-Yuan Road, Nantong, 226019, Jiangsu, China
- Centre for Liver Diseases, Nantong Third People's Hospital, Nantong University, Nantong, China
| | - Yulong Jia
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, 9 Se-Yuan Road, Nantong, 226019, Jiangsu, China
| | - Qi Bao
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, 9 Se-Yuan Road, Nantong, 226019, Jiangsu, China
| | - Jianan Zhu
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, 9 Se-Yuan Road, Nantong, 226019, Jiangsu, China
| | - Lei Zhang
- Research Centre for Public Health, School of Medicine, Tsinghua University, Beijing, China
- Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC, Australia
- Central Clinical School, Faculty of Medicine, Nursing and Health Science, Monash University, Melbourne, Australia
- School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia
| | - Yi Shen
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, 9 Se-Yuan Road, Nantong, 226019, Jiangsu, China.
| |
Collapse
|
|
16
|
Nahon P, Ganne-Carrié N. Management of patients with pre-therapeutic advanced liver fibrosis following HCV eradication. JHEP Rep 2019; 1:480-489. [PMID: 32039400 PMCID: PMC7005771 DOI: 10.1016/j.jhepr.2019.11.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Revised: 10/30/2019] [Accepted: 11/06/2019] [Indexed: 12/19/2022] Open
Abstract
Patients with HCV-related bridging fibrosis or cirrhosis remain at risk of developing life-threatening complications even after achieving a sustained virological response. Although it is reduced, the risk of liver-related events in these patients justifies their inclusion in surveillance programmes dedicated to the early detection of hepatocellular carcinoma and the screening for portal hypertension. Biochemical parameters or non-invasive tests might indicate the potential progression of liver injury despite viral clearance. Specific attention must be focused on the management of comorbidities, while dedicated educational programmes must be encouraged to increase compliance and commitment to surveillance. Better knowledge of the long-term evolution of these patients, who now live longer, is essential to improve risk stratification and refine screening strategies in this growing population.
Collapse
Key Words
- AFP, alpha-fetoprotein
- ALT, alanine aminotransferase
- APRI, AST-to-platelet ratio index
- AST, aspartate aminotransferase
- DAAs, direct-acting antivirals
- EHC, extrahepatic cancer
- FIB-4, fibrosis-4
- HCC, hepatocellular carcinoma
- HCV
- HR, hazard ratio
- Hepatocellular carcinoma
- LSM, liver stiffness measurement
- Liver failure
- MACEs, major adverse cardiovascular events
- PHT, portal hypertension
- Portal hypertension
- SMR, standardised mortality ratio
- SVR
- SVR, sustained virological response
- surveillance
Collapse
Affiliation(s)
- Pierre Nahon
- AP-HP, Hôpital Jean Verdier, Liver Unit, Bondy, France
- University Paris 13, Sorbonne Paris Cité, “équipe labellisée Ligue Contre le Cancer”, F-93000 Bobigny, France
- INSERM UMR-1162: Functional Genomics of Solid Tumours, F-75010, Paris, France
| | - Nathalie Ganne-Carrié
- AP-HP, Hôpital Jean Verdier, Liver Unit, Bondy, France
- University Paris 13, Sorbonne Paris Cité, “équipe labellisée Ligue Contre le Cancer”, F-93000 Bobigny, France
- INSERM UMR-1162: Functional Genomics of Solid Tumours, F-75010, Paris, France
| |
Collapse
|
|
17
|
Lee KK, Stelzle D, Bing R, Anwar M, Strachan F, Bashir S, Newby DE, Shah JS, Chung MH, Bloomfield GS, Longenecker CT, Bagchi S, Kottilil S, Blach S, Razavi H, Mills PR, Mills NL, McAllister DA, Shah ASV. Global burden of atherosclerotic cardiovascular disease in people with hepatitis C virus infection: a systematic review, meta-analysis, and modelling study. Lancet Gastroenterol Hepatol 2019; 4:794-804. [PMID: 31377134 PMCID: PMC6734111 DOI: 10.1016/s2468-1253(19)30227-4] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Revised: 06/26/2019] [Accepted: 06/28/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND More than 70 million people worldwide are estimated to have hepatitis C virus (HCV) infection. Emerging evidence indicates an association between HCV and atherosclerotic cardiovascular disease. We aimed to determine the association between HCV and cardiovascular disease, and estimate the national, regional, and global burden of cardiovascular disease attributable to HCV. METHODS For this systematic review and meta-analysis, we searched MEDLINE, Embase, Ovid Global Health, and Web of Science databases from inception to May 9, 2018, without language restrictions, for longitudinal studies that evaluated the risk ratio (RR) of cardiovascular disease in people with HCV compared with those without HCV. Two investigators independently reviewed and extracted data from published reports. The main outcome was cardiovascular disease, defined as hospital admission with, or mortality from, acute myocardial infarction or stroke. We calculated the pooled RR of cardiovascular disease associated with HCV using a random-effects model. Additionally, we calculated the population attributable fraction and disability-adjusted life-years (DALYs) from HCV-associated cardiovascular disease at the national, regional, and global level. We also used age-stratified and sex-stratified HCV prevalence estimates and cardiovascular DALYs for 100 countries to estimate country-level burden associated with HCV. This study is registered with PROSPERO, number CRD42018091857. FINDINGS Our search identified 16 639 records, of which 36 studies were included for analysis, including 341 739 people with HCV. The pooled RR for cardiovascular disease was 1·28 (95% CI 1·18-1·39). Globally, 1·5 million (95% CI 0·9-2·1) DALYs per year were lost due to HCV-associated cardiovascular disease. Low-income and middle-income countries had the highest disease burden with south Asian, eastern European, north African, and Middle Eastern regions accounting for two-thirds of all HCV-associated cardiovascular DALYs. INTERPRETATION HCV infection is associated with an increased risk of cardiovascular disease. The global burden of cardiovascular disease associated with HCV infection was responsible for 1·5 million DALYs, with the highest burden in low-income and middle-income countries. FUNDING British Heart Foundation and Wellcome Trust.
Collapse
Affiliation(s)
- Kuan Ken Lee
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
| | - Dominik Stelzle
- Department of Neurology, Center for Global Health, Technical University of Munich, Munich, Germany
| | - Rong Bing
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
| | - Mohamed Anwar
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
| | - Fiona Strachan
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
| | - Sophia Bashir
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
| | - David E Newby
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
| | - Jasmit S Shah
- Department of Medicine, Aga Khan University, Nairobi, Kenya
| | | | - Gerald S Bloomfield
- Department of Medicine, Duke Clinical Research Institute and Duke Global Health Institute, Duke University, Durham, NC, USA
| | - Chris T Longenecker
- Division of Cardiology, University Hospitals Harrington Heart and Vascular Institute, School of Medicine, Case Western Reserve University, Cleveland, OH, USA
| | - Shashwatee Bagchi
- Division of Infectious Diseases and Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Shyamasundaran Kottilil
- Division of Infectious Diseases and Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Sarah Blach
- Center for Disease Analysis Foundation, Lafayette, CO, USA
| | - Homie Razavi
- Center for Disease Analysis Foundation, Lafayette, CO, USA
| | - Peter R Mills
- Department of Gastroenterology, Gartnavel General Hospital, NHS Greater Glasgow and Clyde, Glasgow, UK
| | - Nicholas L Mills
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK; Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
| | | | - Anoop S V Shah
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK; Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
| |
Collapse
|
|
18
|
Lövdahl S, Henriksson KM, Baghaei F, Holmström M, Berntorp E, Astermark J. Hypertension and cardiovascular diseases in Swedish persons with haemophilia — A longitudinal registry study. Thromb Res 2019; 181:106-111. [DOI: 10.1016/j.thromres.2019.07.017] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Revised: 06/25/2019] [Accepted: 07/19/2019] [Indexed: 11/28/2022]
|
|
19
|
Revuelto Artigas T, Zaragoza Velasco N, Gómez Arbones X, Vidal Ballester T, Piñol Felis C, Reñe Espinet J, Betriu Bars A. Chronic hepatitis C infection: An independent risk factor for subclinical atheromatosis. Rev Clin Esp 2019. [DOI: 10.1016/j.rceng.2019.02.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
20
|
Factor VIII: Long-established role in haemophilia A and emerging evidence beyond haemostasis. Blood Rev 2019; 35:43-50. [DOI: 10.1016/j.blre.2019.03.002] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Revised: 02/01/2019] [Accepted: 03/01/2019] [Indexed: 12/20/2022]
|
|
21
|
Wen D, Du X, Dong JZ, Ma CS. Hepatitis C virus infection and risk of coronary artery disease: A meta-analysis. Eur J Intern Med 2019; 63:69-73. [PMID: 31006509 DOI: 10.1016/j.ejim.2019.03.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Revised: 01/08/2019] [Accepted: 03/05/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND A few recent studies have demonstrated that hepatitis C virus (HCV) infection was associated with coronary artery diseases (CAD). However, there still existed studies did not confirm this correlation. OBJECTIVE The objective of this study was to evaluate the association between HCV infection and CAD using a meta-analysis. METHODS Pubmed, Embase, and Cochrane library databases were systemically searched. Data were extracted by two independent reviewers and pooled odds ratio (OR) and relative risk (RR) with 95% confidence interval (CI) were calculated using the fixed and random effects models. RESULTS Eight cohort studies and six case-control and cross-sectional studies were enrolled in this meta-analysis. In the cohort studies, the overall RR and 95% CIs of HCV infection for CAD was 1.25, 1.12-1.40 in random effects model. For the case-control and cross-sectional studies, the overall OR and 95% CIs of HCV infection for CAD were 1.94, 1.58-2.38 in fixed effects model. No publication bias was found in this meta-analysis. CONCLUSIONS This meta-analysis showed that HCV infection was a risk factor for CAD.
Collapse
Affiliation(s)
- Dan Wen
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China
| | - Xin Du
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China
| | - Jian-Zeng Dong
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China
| | - Chang-Sheng Ma
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China.
| |
Collapse
|
|
22
|
Revuelto Artigas T, Zaragoza Velasco N, Gómez Arbones X, Vidal Ballester T, Piñol Felis C, Reñe Espinet JM, Betriu Bars A. Chronic hepatitis C infection: An independent risk factor for subclinical atheromatosis. Rev Clin Esp 2019; 219:293-302. [PMID: 30773286 DOI: 10.1016/j.rce.2018.12.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Revised: 09/27/2018] [Accepted: 12/04/2018] [Indexed: 01/20/2023]
Abstract
BACKGROUND The association between subclinical atheromatosis and chronic hepatitis C virus (HCV) infection is unknown but is relevant now that antivirals are improving the survival of patients with the infection. OBJECTIVES To determine whether HCV is an independent risk factor for subclinical atheromatosis and to analyse the changes in lipid profiles according to viral RNA levels and hepatic fibrosis. PATIENTS AND METHODS We conducted an observational, cross-sectional study that included 102 HCV-positive patients and 102 HCV-negative patients with parity in terms of sex and age, with no history of cardiovascular or kidney disease or diabetes. Atheromatosis (the presence of atheromatous plaques) and the carotid intima-media thickness (CIMT) were assessed using ultrasonography of the carotid and femoral arteries. RESULTS There was a greater presence of atheromatosis in any vascular territory in HCV-positive patients than in the patients without infection (58.8% vs. 28.4%, p<.0001). In the multivariate analysis, the factors significantly associated with atheromatosis included HCV infection (OR, 14.37 [5.5-37.3]; p<.001), age (OR, 1.12 [1.1-1.2]; p<.001), male sex (OR, 4.32 [1.9-9.5]; p<.001) and the triglyceride/HDL cholesterol coefficient (TG/HDL-indirect indicator of insulin resistance) (OR, 1.34 [1.1-1.6]; p=.007). The HCV-positive patients with atheromatous plaques had a higher TG/HDL coefficient but no significant differences in terms of the viral load or degree of hepatic fibrosis and with a 'low risk' lipid profile. CONCLUSIONS HCV infection is an independent risk factor for subclinical atheromatosis. Systemic arterial ultrasonography for this population improves the cardiovascular risk assessment beyond lipid profile abnormalities and the risk calculation using SCORE tables.
Collapse
Affiliation(s)
- T Revuelto Artigas
- Servicio de Aparato Digestivo, Hospital Universitario Santa María, Lleida, España; Servicio de Aparato Digestivo, Hospital Universitario Arnau de Vilanova, Lleida, España; Unidad de Detección y Tratamiento de Enfermedades Aterotrombóticas (UDETMA), Hospital Universitario Arnau de Vilanova (Grupo de Investigación Translacional Vascular y Renal, IRBLleida), Lleida, España; Instituto de Investigación Biomédica, Lleida, España.
| | - N Zaragoza Velasco
- Servicio de Aparato Digestivo, Hospital Universitario Arnau de Vilanova, Lleida, España; Unidad de Detección y Tratamiento de Enfermedades Aterotrombóticas (UDETMA), Hospital Universitario Arnau de Vilanova (Grupo de Investigación Translacional Vascular y Renal, IRBLleida), Lleida, España; Instituto de Investigación Biomédica, Lleida, España
| | - X Gómez Arbones
- Instituto de Investigación Biomédica, Lleida, España; Universidad de Lleida (UdL), Lleida, España
| | - T Vidal Ballester
- Unidad de Detección y Tratamiento de Enfermedades Aterotrombóticas (UDETMA), Hospital Universitario Arnau de Vilanova (Grupo de Investigación Translacional Vascular y Renal, IRBLleida), Lleida, España
| | - C Piñol Felis
- Instituto de Investigación Biomédica, Lleida, España; Universidad de Lleida (UdL), Lleida, España
| | - J M Reñe Espinet
- Servicio de Aparato Digestivo, Hospital Universitario Arnau de Vilanova, Lleida, España; Instituto de Investigación Biomédica, Lleida, España; Universidad de Lleida (UdL), Lleida, España
| | - A Betriu Bars
- Unidad de Detección y Tratamiento de Enfermedades Aterotrombóticas (UDETMA), Hospital Universitario Arnau de Vilanova (Grupo de Investigación Translacional Vascular y Renal, IRBLleida), Lleida, España; Instituto de Investigación Biomédica, Lleida, España
| |
Collapse
|
|
23
|
Hamed AE, Elsahar M, Elwan NM, El-Nakeep S, Naguib M, Soliman HH, Ahmed Aboubakr A, AbdelMaqsod A, Sedrak H, Assaad SN, Elwakil R, Esmat G, Salh S, Mostafa T, Mogawer S, Sadek SE, Saber MM, Ezelarab H, Mahmoud AA, Sultan S, El Kassas M, Kamal E, ElSayed NM, Moussa S. Managing diabetes and liver disease association. Arab J Gastroenterol 2018; 19:166-179. [PMID: 30420265 DOI: 10.1016/j.ajg.2018.08.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Accepted: 08/26/2018] [Indexed: 02/05/2023]
Abstract
There is strong association between liver diseases and diabetes (DM) which is higher than expected by a chance association of two very common disorders. It can be classified into three categories: Liver disease related to diabetes, hepatogenous diabetes (HD), and liver disease occurring coincidentally with DM. The criteria for the diagnosis of diabetes associating liver disease are the same for primary diabetes. Two hours post glucose load is a better screening test for HD. HbA1c may not be suitable for diagnosis or monitoring of diabetes associating advanced liver disease. Apart from the increased cardiovascular risk in patients with type 2 DM (T2 DM) and NAFLD, the cardiovascular and retinopathy risk is low in HD. Patients with metabolic derangement should be screened for NAFLD which in turn may predict T2 DM development. Similarly, patients with established T2 DM should also be screened for NAFLD which further contributes to diabetes worsening. Diabetes is a significant risk factor for progression of the chronic liver disease. It is associated with poor patient survival. Treatment of diabetes associating liver disease appears beneficial. Metformin, if tolerated and not contraindicated, is recommended as a first-line therapy for patients with diabetes and chronic liver disease (CLD). If the hepatic disease is severe, insulin secretagogues should be avoided because of the increased risk of hypoglycaemia. Pioglitazone may be useful in patients with fatty liver disease. DPP-4 inhibitors showed effectiveness and safety for the treatment of T2 DM in CLD patients up to those with child B stage. GLP-1 receptor agonists and SGLT-2 inhibitors exhibit positive effects on weight and are associated with minimal risk of hypoglycaemia. Insulin must be used with caution, as hypoglycaemia may be a problem. Insulin analogues are preferred in the context of hypoglycaemia Statins can be used to treat dyslipidaemia in NAFLD, also the use of angiotensin II receptor antagonist for hypertension is safe and beneficial Given the clear association between diabetes mellitus and hepatocellular carcinoma, the strict control of glycaemia with insulin sensitizers can be essential in its prevention. The addition of DM to the currently used scores (Child-Pugh and MELD scores) may enhance the sensitivity and the specificity for prediction of morbidity and mortality rates in cirrhotic patients. In the new era of directly acting antiviral agents (DAAs) for HCV treatment, it is recommended to follow up lipid profile and blood sugar levels following SVR in order to adjust doses of medications used in diabetic (SVR is associated with reduction in insulin requirements) and dyslipidaemic patients (rebound increase in the lipid profile after clearing the virus may increase risk of cardiovascular disease (CVD)). The issues of post liver transplant diabetes and relation between DM and chronic HBV are highlighted. This narrative review and Consensus-based practice guidance (under revision and criticism) are based on a formal review and analysis of the recently published world literature on the topic (Medline search up to September 2017); and the experience of the authors and independent reviewers.
Collapse
Affiliation(s)
- Abd Elkhalek Hamed
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt.
| | - Medhat Elsahar
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Police Medical Academy, Egypt
| | | | | | | | | | - Ashraf Ahmed Aboubakr
- Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt
| | | | | | | | - Reda Elwakil
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Ain Shams University, Egypt
| | - Gamal Esmat
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Kasr Al Aini, Egypt
| | - Samira Salh
- Department of Pharmacy, Cairo University, Egypt
| | | | | | - Sameh Emil Sadek
- Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt
| | - Maha M Saber
- Department of Clinical Nutrition National Research Centre, Egypt
| | - Hanan Ezelarab
- Department of Clinical Nutrition National Research Centre, Egypt
| | - Asem Ashraf Mahmoud
- Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt
| | | | | | - Ehab Kamal
- Medical Department, National Research Centre, Egypt
| | | | | |
Collapse
|
|
24
|
|
|
25
|
Zubkin ML, Chervinko VI, Ovchinnikov YV, Kryukov EV, Kotenko ON. [Chronic HCV infection: An internist's opinion (Part 2)]. TERAPEVT ARKH 2018. [PMID: 28635834 DOI: 10.17116/terarkh20168811138-148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Hepatitis C virus (HCV) infection results in not only chronic hepatitis and subsequent complications as liver cirrhosis and hepatocellular carcinoma, but also in a significant number of other diseases, the so-called extrahepatic manifestations of chronic HCV infection. In addition to lymphoproliferative and autoimmune disorders discussed in Part 1 of this review, many other diseases turned to be associated with chronic HCV infection. Part 2 of this review is dedicated to the analysis of the relationship of chronic HCV-infection to the development of some endocrine diseases, such as thyroiditis and diabetes mellitus, and cardiovascular disorders. It also provides the characteristics of the currently available antiviral agents and considers whether they may be used in patents with extrahepatic manifestations of chronic HCV infection.
Collapse
Affiliation(s)
- M L Zubkin
- G.N. Gabrichevsky Moscow Research Institute for Epidemiology and Microbiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare, Moscow, Russia; Branch, S.M. Kirov Military Medical Academy, Moscow, Russia
| | - V I Chervinko
- Branch, S.M. Kirov Military Medical Academy, Moscow, Russia
| | | | - E V Kryukov
- N.N. Burdenko Main Military Clinical Hospital, Moscow, Russia
| | - O N Kotenko
- City Clinical Hospital Fifty-Two, Moscow Healthcare Department, Moscow, Russia
| |
Collapse
|
|
26
|
Gadallah M, Kandil S, Mohsen A. Association between hepatitis C infection and cerebro-cardiovascular disease: analysis of a national population-based survey in Egypt. Trop Med Int Health 2018; 23:738-747. [PMID: 29723920 DOI: 10.1111/tmi.13068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES To examine the association between hepatitis C virus (HCV) infection, cardiovascular risk factors and cerebro-cardiovascular (CCV) disease. METHODS The source of data was the Egypt Health Issues Survey conducted in 2015. Participants were 11 256 individuals with complete HCV testing, age 25-59 years. Data on demographics, cardiovascular risk factors, CCV disease (myocardial infarction and/or cerebral stroke) and HCV infection were retrieved. Descriptive, bivariate, multivariable logistic regression and sensitivity analyses were performed to determine the independent association of past HCV exposure or chronic infection with diabetes, hypertension and CCV disease. RESULTS 3.9% of participants were antibody positive/RNA negative and considered to have past HCV exposure; 7.9% had detectable HCV-RNA and were considered to have chronic infection. Participants with negative antibodies and no history of liver disease (n = 9928) were the control group. In addition to the previously known risk factors, multivariable analyses revealed that diabetes was independently associated with past HCV exposure (OR = 1.71, 95% CI: 1.27-2.32) and HCV chronic infection (OR = 1.56, 95% CI: 1.23-1.97), whereas CCV disease was independently associated with past exposure (OR = 2.69, 95% CI: 1.62-4.46) and not with chronic infection. No evidence of an association between hypertension and either HCV status was found. CONCLUSION The association of both past HCV exposure and chronic infection with diabetes and that of past HCV exposure with CCV disease may suggest targeting HCV-positive reactors for preventive and curative programmes addressing extrahepatic complications.
Collapse
Affiliation(s)
- Mohsen Gadallah
- Department of Community, Environmental and Occupational Medicine, Ain Shams University, Cairo, Egypt
| | - Sahar Kandil
- Department of Community, Environmental and Occupational Medicine, Ain Shams University, Cairo, Egypt
| | | |
Collapse
|
|
27
|
Cacoub P, Nahon P, Layese R, Blaise L, Desbois AC, Bourcier V, Cagnot C, Marcellin P, Guyader D, Pol S, Larrey D, De Lédinghen V, Ouzan D, Zoulim F, Roulot D, Tran A, Bronowicki JP, Zarski JP, Riachi G, Calès P, Péron JM, Alric L, Bourlière M, Mathurin P, Blanc JF, Abergel A, Serfaty L, Mallat A, Grangé JD, Attali P, Bacq Y, Wartelle C, Dao T, Thabut D, Pilette C, Silvain C, Christidis C, Capron D, Thiefin G, Zucman D, Di Martino V, Bagnis CI, Ziol M, Sutton A, Letouze E, Roudot-Thoraval F, Audureau E. Prognostic value of viral eradication for major adverse cardiovascular events in hepatitis C cirrhotic patients. Am Heart J 2018; 198:4-17. [PMID: 29653647 DOI: 10.1016/j.ahj.2017.10.024] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Accepted: 10/29/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND The objective was to examine the role of a sustained virological response (SVR) on major adverse cardiovascular events (MACEs) in patients with compensated hepatitis C virus (HCV) cirrhosis. METHODS Patients with the following criteria were enrolled in 35 French centers: (1) biopsy-proven HCV cirrhosis; (2) Child-Pugh A; (3) positive viremia; and (4) no prior liver complication, and then prospectively followed. All patients received HCV treatment after inclusion. MACEs included stroke, myocardial infarction, ischemic heart disease, heart failure, peripheral arterial disease, cardiac arrest, and cardiovascular death. SVR, defined as negative viremia 12 weeks posttreatment, was considered as a time-dependent covariate, and its effect on MACE occurrence was assessed. The median follow up was 57.5 months, ending in December 2015. RESULTS Sixty-two of 878 (7.1%) patients presented a total of 79 MACEs. The main predictive baseline factors of MACEs were Asian ethnic origin, history of MACEs, arterial hypertension, diabetes mellitus, current smoking, low serum albumin level, high total bilirubin level, and low platelet count. In multivariate analysis, SVR was associated with a decreased risk of MACEs (hazard ratio=0.35, 95% CI 0.09-0.97, P=.044), whereas Asian ethnic origin, arterial hypertension, smoking, and low serum albumin level remained predictive of MACE occurrence. The 5-year survival rate was 60.1% versus 87.5% in patients who did versus those who did not present a MACE (P<.001). CONCLUSIONS In patients with compensated HCV-related cirrhosis, Asian ethnic origin, arterial hypertension, smoking, and low serum albumin are independent predictive factors of cardiovascular events, whereas an SVR is associated with a decreased rate of cardiovascular events.
Collapse
Affiliation(s)
- Patrice Cacoub
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR_S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France.
| | - Pierre Nahon
- AP-HP, Hôpital Jean Verdier, Service d'Hépatologie, Bondy; Université Paris 13, Sorbonne Paris Cité, "Equipe labellisée Ligue Contre le Cancer", Saint-Denis; Inserm, UMR-1162, "Génomique fonctionnelle des tumeur solides", Paris
| | - Richard Layese
- AP-HP, Hôpital Henri Mondor, Unité de Recherche Clinique (URC-Mondor), and Université Paris-Est, A-TVB DHU, CEpiA (Clinical Epidemiology and Aging) Unit EA4393, UPEC, Créteil
| | | | - Anne Claire Desbois
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR_S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | | | - Carole Cagnot
- Unit for Basic and Clinical research on Viral Hepatitis, ANRS (France REcherche Nord & sud Sida-HIV Hépatites-FRENCH)
| | | | | | - Stanislas Pol
- Université Paris Descartes, APHP, Unité d'Hépatologie, Hôpital Cochin, INSERM U-1223 et USM20, Institut Pasteur, Paris, France
| | | | | | - Denis Ouzan
- Institut Arnaud Tzanck, Service d'Hépatologie, St Laurent du Var
| | | | | | - Albert Tran
- Institut National de la Santé et de la Recherche Médicale (INSERM), U1065, Team 8, "Hepatic Complications in Obesity", Nice, France and University Hospital of Nice, Digestive Centre, Nice, France
| | | | | | - Ghassan Riachi
- Hôpital Charles-Nicolle, Service d'Hépato-gastro-entérologie, Rouen
| | - Paul Calès
- CHU d'Angers, Service d'Hépatologie, Angers
| | | | - Laurent Alric
- Service de Médecine Interne-Pôle Digestif CHU Toulouse, UMR 152, IRD, Toulouse 3 University
| | | | | | | | - Armand Abergel
- Hôpital Hôtel Dieu, Service d'Hépatologie, Clermont-Ferrand
| | | | - Ariane Mallat
- AP-HP, Hôpital Henri Mondor, Service d'Hépatologie, Créteil
| | | | - Pierre Attali
- AP-HP, Hôpital Paul Brousse, Service d'Hépatologie, Villejuif
| | - Yannick Bacq
- Hôpital Trousseau, Unité d'Hépatologie, CHRU de Tours
| | - Claire Wartelle
- Hôpital d'Aix-En-Provence, Service d'Hépatologie, Aix-En-Provence
| | - Thông Dao
- Hôpital de la Côte de Nacre, Service d'Hépatologie, Caen
| | - Dominique Thabut
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; AP-HP, Groupe Hospitalier de La Pitié-Salpêtrière, Service d'Hépatologie, Paris
| | | | | | | | | | | | | | | | - Corinne Isnard Bagnis
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Nephrology, Paris, France
| | - Marianne Ziol
- Inserm, UMR-1162, "Génomique fonctionnelle des tumeur solides", Paris; AP-HP, Hôpital Jean Verdier, Service d'Anatomopathologie, Bondy; CRB (liver disease biobank) Groupe Hospitalier Paris Seine-Saint-Denis BB-0033-00027
| | - Angela Sutton
- CRB (liver disease biobank) Groupe Hospitalier Paris Seine-Saint-Denis BB-0033-00027; AP-HP, Hôpital Jean Verdier, Service de Biochimie, Bondy
| | - Eric Letouze
- Inserm, UMR-1162, "Génomique fonctionnelle des tumeur solides", Paris
| | - Françoise Roudot-Thoraval
- AP-HP, Hôpital Henri Mondor, Unité de Recherche Clinique (URC-Mondor), and Université Paris-Est, A-TVB DHU, CEpiA (Clinical Epidemiology and Aging) Unit EA4393, UPEC, Créteil
| | - Etienne Audureau
- AP-HP, Hôpital Henri Mondor, Unité de Recherche Clinique (URC-Mondor), and Université Paris-Est, A-TVB DHU, CEpiA (Clinical Epidemiology and Aging) Unit EA4393, UPEC, Créteil
| |
Collapse
|
|
28
|
Alvaro-Meca A, Ryan P, Martínez-Larrull E, Micheloud D, Berenguer J, Resino S. Epidemiological trends of deep venous thrombosis in HIV-infected subjects (1997-2013): A nationwide population-based study in Spain. Eur J Intern Med 2018; 48:69-74. [PMID: 29102088 DOI: 10.1016/j.ejim.2017.10.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Revised: 10/09/2017] [Accepted: 10/16/2017] [Indexed: 11/27/2022]
Abstract
BACKGROUND Chronic infections may be a triggering factor as well as a risk factor of deep venous thrombosis (DVT). The purpose of this study was to analyze the epidemiological trends of hospital admissions related to DVT in human immunodeficiency virus (HIV)-infected patients during the combination antiretroviral therapy (cART) era, in relation to hepatitis C virus (HCV) serological status. METHODS We performed a retrospective study using the Spanish Minimum Basic Data Set. We selected HIV-infected subjects over 15years old with a hospital admission and DVT diagnosis (ICD-9-CM codes: 453.4x and 453.8x) between 1997 and 2013. Patients were classified according to HCV serology. We estimated the incidence (events per 100,000 patient-years) in four calendar periods (1997-1999, 2000-2003, 2004-2007, and 2008-2013). RESULTS Overall, the incidence of DVT-related hospitalizations had a significant upward trend in all HIV-infected patients (P<0.001), with significant differences between 1997-1999 and 2008-2013 [49.5 vs. 88.1 (P<0.001)]. Moreover, the incidence was higher in HIV-monoinfected patients than in HIV/HCV-coinfected patients during the entire follow-up (P<0.001). However, the incidence had a significant downward trend in HIV-monoinfected patients (P=0.002) and a significant upward trend in HIV/HCV-coinfected patients (P<0.001). Specifically, the incidence of DVT-related hospitalizations in HIV-monoinfected patients significantly decreased from 1997-1999 to 2008-2013 [142.7 vs. 103.1 (P=0.006)], whereas in HIV/HCV-coinfected patients, the incidence increased from 8.4 (1997-1999) to 70.7 (2008-2013) (P<0.001). CONCLUSIONS Our findings suggest that DVT is an emerging health problem among HIV-infected patients, with increasing incidence during the first 17years after the introduction of cART, particularly in HIV/HCV-coinfected patients.
Collapse
Affiliation(s)
- Alejandro Alvaro-Meca
- Unidad de Medicina Preventiva y Salud Pública, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain
| | - Pablo Ryan
- Servicio de Medicina Interna, Hospital Universitario Infanta Leonor, Madrid, Spain
| | | | - Dariela Micheloud
- Servicio de Urgencias, Hospital General Universitario "Gregorio Marañón", Madrid, Spain
| | - Juan Berenguer
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Salvador Resino
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
| |
Collapse
|
|
29
|
Kuo SH, Hung WT, Tang PL, Huang WC, Yang JS, Lin HC, Mar GY, Chang HT, Liu CP. Impact of hepatitis C virus infection on long-term mortality after acute myocardial infarction: a nationwide population-based, propensity-matched cohort study in Taiwan. BMJ Open 2018; 8:e017412. [PMID: 29374659 PMCID: PMC5829782 DOI: 10.1136/bmjopen-2017-017412] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION The influence of hepatitis C virus (HCV) infection on long-term outcomes of patients with acute myocardial infarction (AMI) is unclear. Therefore, this study aimed to analyse the impact of HCV infection on 12-year mortality rates after AMI using data from the Taiwan National Health Insurance Research Database (NHIRD). METHODS NHIRD data for approximately 23 000 000 patients between January 2000 and December 2012 were analysed. A total of 186 112 cases of first AMI admission were identified. A total of 4659 patients with HCV infection not receiving interferon therapy were enrolled and divided into those with (n=107) or without (n=4552) cirrhosis. Using one-to-one matching, 4552 matched controls were included in the final analysis. RESULTS The 12-year mortality rate was significantly higher in patients with AMI with HCV infection and cirrhosis than in those with HCV infection but without cirrhosis (P<0.0001) or controls (P<0.0001). Patients with HCV infection but without cirrhosis had significantly higher long-term mortality rates than the matched controls (P<0.0001). The HR for mortality was higher in patients with HCV infection (HR 1.12; 95% CI 1.06 to 1.18). HCV influenced outcomes among the subgroups of patients who were male (HR 1.15) and those who had hypertension (HR 1.14). CONCLUSIONS HCV infection influenced the 12-year mortality rates of patients with AMI, especially those who were male and those who had hypertension. Cirrhosis further increased the long-term mortality rates of patients with AMI with HCV infection.
Collapse
Affiliation(s)
- Shu-Hung Kuo
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Wang-Ting Hung
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Pei-Ling Tang
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Wei-Chun Huang
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Department of Physical Therapy, Fooyin University, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Jin-Shiou Yang
- Department of Physical Therapy, Fooyin University, Kaohsiung, Taiwan
| | - Hsiao-Chin Lin
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Guang-Yuan Mar
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Hong-Tai Chang
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Chun-Peng Liu
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| |
Collapse
|
|
30
|
Babiker A, Jeudy J, Kligerman S, Khambaty M, Shah A, Bagchi S. Risk of Cardiovascular Disease Due to Chronic Hepatitis C Infection: A Review. J Clin Transl Hepatol 2017; 5:343-362. [PMID: 29226101 PMCID: PMC5719192 DOI: 10.14218/jcth.2017.00021] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Revised: 07/15/2017] [Accepted: 07/27/2017] [Indexed: 12/17/2022] Open
Abstract
Hepatitis C (HCV) infection has an estimated global prevalence of 2.5%, causing chronic liver disease in 170 million people worldwide. Recent data has identified HCV infection as a risk factor for subclinical and clinical cardiovascular disease (CVD), but these data have been mixed and whether HCV is an independent risk factor for development of CVD remains controversial. In this review, we present the literature regarding the association of HCV with subclinical and clinical CVD and the possible underlying mechanisms leading to increased CVD among those infected with HCV. HCV infection leads to increased CVD via direct and indirect mechanisms with chronic inflammation, endothelial dysfunction and direct invasion of the arterial wall cited as possible mechanisms. Our review showed that HCV infection, particularly chronic HCV infection, appears to lead to increased subclinical CVD most consistently and potentially also to increased clinical CVD outcomes, leading to increased morbidity and mortality. Furthermore, the majority of studies evaluating the impact of HCV therapy on CVD morbidity and mortality showed an improvement in subclinical and clinical CVD endpoints in patients who were successfully treated and achieved sustained viral suppression. These results are of particular interest following the development of new direct antiviral agents which have made HCV eradication simple and feasible for many more patients globally, and in doing so may possibly reduce CVD morbidity and mortality in those with chronic HCV infection.
Collapse
Affiliation(s)
| | - Jean Jeudy
- Department of Radiology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Seth Kligerman
- Department of Radiology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Miriam Khambaty
- Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, MD, USA
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Anoop Shah
- Division of Cardiology, University of Edinburgh, Little France, Edinburgh
| | - Shashwatee Bagchi
- Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, MD, USA
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
- *Correspondence to: Shashwatee Bagchi, Division of Infectious Diseases, University of Maryland School of Medicine, 725 West Lombard Street, N359, Baltimore, MD 21201, USA. Tel: +1-410-706-4606, Fax: +1-410-706-3243, E-mail:
| |
Collapse
|
|
31
|
Bedimo R, Abodunde O. Metabolic and Cardiovascular Complications in HIV/HCV-Co-infected Patients. Curr HIV/AIDS Rep 2017; 13:328-339. [PMID: 27595755 DOI: 10.1007/s11904-016-0333-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE OF REVIEW Fifteen to thirty percent of HIV-infected persons in North America and Europe are co-infected with chronic hepatitis C (HCV). The latter is associated with a significant number of extra-hepatic metabolic complications that could compound HIV-associated increased cardiovascular risk. This article reviews the basic science and epidemiologic and clinical evidence for increased cardio-metabolic risk among HIV/HCV-co-infected patients and discusses potential underlying mechanisms. We will finally review the impact of control of HCV viremia on the cardio-metabolic morbidity and mortality of HIV/HCV-co-infected patients. RECENT FINDINGS HCV infection is associated with a number of immune-related complications such as cryoglobulinemia but also metabolic complications including dyslipidemias, hepatic steatosis, insulin resistance, diabetes, and chronic kidney disease. The incidence of these complications is higher among HIV-co-infected patients and might contribute to increased mortality. The potential mechanisms of increased cardiovascular risk among HIV/HCV-co-infected subjects include endothelial dysfunction, chronic inflammation and immune activation, the cardio-metabolic effects of HCV-induced hepatic steatosis and fibrosis or insulin resistance, and chronic kidney disease. However, epidemiologic studies show discordant findings as to whether HCV co-infection further increases the risk of atherosclerotic cardiovascular diseases (acute myocardial infarctions and strokes) among HIV-infected patients. Nonetheless, successful treatment of HCV is associated with significant improvements in cardio-metabolic risk factors including diabetes mellitus. HCV co-infection is associated with a higher incidence of metabolic complications-and likely increased risk of cardiovascular events-that might contribute to increased mortality in HIV. These appear to improve with successful HCV therapy.
Collapse
Affiliation(s)
- Roger Bedimo
- Infectious Diseases Section, Medical Service, Veterans Affairs North Texas Healthcare System, Dallas, TX, USA. .,Department of Internal Medicine, Division of Infectious Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA.
| | - Oladapo Abodunde
- Infectious Diseases Section, Medical Service, Veterans Affairs North Texas Healthcare System, Dallas, TX, USA.,Department of Internal Medicine, Division of Infectious Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA
| |
Collapse
|
|
32
|
Abstract
Hepatitis C virus (HCV) infection is a prevalent condition associated with numerous extrahepatic manifestations. Epidemiologic studies have found that HCV is associated with increased cardiovascular morbidity and mortality, in particular with carotid atherosclerosis, cerebrovascular events, and coronary heart disease. The mechanisms involved encompass a chronic systemic inflammatory state, insulin resistance, and a potential, direct infection of the vascular endothelium. Sustained virologic response with interferon-based regimens is associated with reduced cardiovascular events, although this must be validated with newer direct-acting antivirals. This clear association between HCV and cardiovascular events may have significant economical and public health implications.
Collapse
Affiliation(s)
- Nicolas Goossens
- Division of Gastroenterology and Hepatology, Geneva University Hospitals, 4 Rue Gabrielle-Perret-Gentil, Geneva 4 1211, Switzerland
| | - Francesco Negro
- Division of Gastroenterology and Hepatology, Geneva University Hospitals, 4 Rue Gabrielle-Perret-Gentil, Geneva 4 1211, Switzerland; Division of Clinical Pathology, Geneva University Hospitals, 4 Rue Gabrielle-Perret-Gentil, Geneva 4 1211, Switzerland.
| |
Collapse
|
|
33
|
Berenguer J, Rodríguez‐Castellano E, Carrero A, Von Wichmann MA, Montero M, Galindo MJ, Mallolas J, Crespo M, Téllez MJ, Quereda C, Sanz J, Barros C, Tural C, Santos I, Pulido F, Guardiola JM, Rubio R, Ortega E, Montes ML, Jusdado JJ, Gaspar G, Esteban H, Bellón JM, González‐García J. Eradication of hepatitis C virus and non-liver-related non-acquired immune deficiency syndrome-related events in human immunodeficiency virus/hepatitis C virus coinfection. Hepatology 2017; 66:344-356. [PMID: 28109003 PMCID: PMC5575524 DOI: 10.1002/hep.29071] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2016] [Revised: 01/11/2017] [Accepted: 01/15/2017] [Indexed: 02/06/2023]
Abstract
UNLABELLED We assessed non-liver-related non-acquired immunodeficiency syndrome (AIDS)-related (NLR-NAR) events and mortality in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients treated with interferon (IFN) and ribavirin (RBV), between 2000 and 2008. The censoring date was May 31, 2014. Cox regression analysis was performed to assess the adjusted hazard rate (HR) of overall death in responders and nonresponders. Fine and Gray regression analysis was conducted to determine the adjusted subhazard rate (sHR) of NLR deaths and NLR-NAR events considering death as the competing risk. The NLR-NAR events analyzed included diabetes mellitus, chronic renal failure, cardiovascular events, NLR-NAR cancer, bone events, and non-AIDS-related infections. The variables for adjustment were age, sex, past AIDS, HIV transmission category, nadir CD4+ T-cell count, antiretroviral therapy, HIV RNA, liver fibrosis, HCV genotype, and exposure to specific anti-HIV drugs. Of the 1,625 patients included, 592 (36%) had a sustained viral response (SVR). After a median 5-year follow-up, SVR was found to be associated with a significant decrease in the hazard of diabetes mellitus (sHR, 0.57; 95% confidence interval [CI], 0.35-0.93; P = 0.024) and decline in the hazard of chronic renal failure close to the threshold of significance (sHR, 0.43; 95% CI, 0.17-1.09; P = 0.075). CONCLUSION Our data suggest that eradication of HCV in coinfected patients is associated not only with a reduction in the frequency of death, HIV progression, and liver-related events, but also with a reduced hazard of diabetes mellitus and possibly of chronic renal failure. These findings argue for the prescription of HCV therapy in coinfected patients regardless of fibrosis stage. (Hepatology 2017;66:344-356).
Collapse
Affiliation(s)
- Juan Berenguer
- Hospital General Universitario Gregorio MarañónMadridSpain,Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM)MadridSpain
| | | | - Ana Carrero
- Hospital General Universitario Gregorio MarañónMadridSpain,Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM)MadridSpain
| | | | | | | | | | - Manuel Crespo
- Complexo Hospitalario Universitario de VigoVigoSpain
| | | | | | - José Sanz
- Hospital Universitario Príncipe de AsturiasAlcalá de HenaresSpain
| | | | - Cristina Tural
- Hospital Universitari Germans Trias i PujolBadalonaSpain
| | | | | | | | - Rafael Rubio
- Hospital Universitario 12 de Octubre (imas12)MadridSpain
| | | | | | | | | | | | - José M. Bellón
- Hospital General Universitario Gregorio MarañónMadridSpain,Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM)MadridSpain
| | | | | |
Collapse
|
|
34
|
Alvaro-Meca A, Berenguer J, Díaz A, Micheloud D, Aldámiz-Echevarría T, Fanciulli C, Resino S. Stroke in HIV-infected individuals with and without HCV coinfection in Spain in the combination antiretroviral therapy era. PLoS One 2017; 12:e0179493. [PMID: 28617855 PMCID: PMC5472313 DOI: 10.1371/journal.pone.0179493] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Accepted: 05/31/2017] [Indexed: 12/22/2022] Open
Abstract
The incidence of stroke in human immunodeficiency virus (HIV)–infected individuals has been well analyzed in recent epidemiological studies. However, little is known about the specific contribution of hepatitis C virus (HCV) infection to stroke among HIV-infected individuals. The aims of this study were to analyze trends in the incidence rates of stroke in HIV-infected individuals during the combination antiretroviral (cART) era in Spain and to categorize them by the presence or absence of HCV coinfection. We analyzed hospital discharges with a diagnosis of stroke in Spain according to ICD-9-CM during 1997–2013. The study period was divided into four calendar periods (1997–1999, 2000–2003, 2004–2007, and 2008–2013). Patients were classified according to HCV serology. The number of HIV-infected patients was estimated based on data from the National Centre of Epidemiology. We calculated incidence rates (events per 10,000 patient-years) and in-hospital case fatality rates (CFR). The incidence of hemorrhagic stroke (HS) decreased in HIV-monoinfected patients (15.8 [1997–1999] to 6.5 [2008–2013]; P<0.001) and increased in HIV/HCV-coinfected patients (1.3 [1997–1999] to 5.5 [2008–2013]; P<0.001). The incidence of ischemic stroke (IS) decreased in HIV-monoinfected patients (27.4 [1997–1999] to 21.7 [2008–2013]; P = 0.005) and increased in HIV/HCV-coinfected patients (1.8 [1997–1999] to 11.9 [2008–2013]; P<0.001). The CFR was 3.3 times higher for HS than for IS for the whole study period. The CFR of HS in HIV-monoinfected patients decreased significantly (47.4% [1997–1999] to 30.6% [2008–2013]; P = 0.010) but did not change significantly among HIV/HCV-coinfected patients (41.4% [1997–1999] to 44.7% [2008–2013]; P = 0.784). The CFR of IS in the whole HIV-infected population decreased significantly (14.6% [1997–1999] to 10.9% [2008–2013]; P = 0.034), although no significant differences were found when each group was analyzed separately. In conclusion, after the introduction of cART, HS and IS rates decreased in HIV-monoinfected individuals, but increased steadily in HIV/HCV-coinfected individuals.
Collapse
Affiliation(s)
- Alejandro Alvaro-Meca
- Unidad de Medicina Preventiva y Salud Pública, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain
| | - Juan Berenguer
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario Gregorio Marañón, Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
- * E-mail:
| | - Asunción Díaz
- Área de Vigilancia Epidemiológica de VIH/SIDA y comportamientos de riesgo, Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Madrid, Spain
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - Dariela Micheloud
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
- Servicio de Medicina Interna, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Teresa Aldámiz-Echevarría
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario Gregorio Marañón, Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Chiara Fanciulli
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario Gregorio Marañón, Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Salvador Resino
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| |
Collapse
|
|
35
|
Desbois AC, Cacoub P. Diabetes mellitus, insulin resistance and hepatitis C virus infection: A contemporary review. World J Gastroenterol 2017; 23:1697-1711. [PMID: 28321170 PMCID: PMC5340821 DOI: 10.3748/wjg.v23.i9.1697] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Revised: 11/10/2016] [Accepted: 02/08/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To summarise the literature data on hepatitis C virus (HCV)-infected patients concerning the prevalence of glucose abnormalities and associated risk.
METHODS We conducted a PubMed search and selected all studies found with the key words "HCV" or "hepatitis C virus" and "diabetes" or "insulin resistance". We included only comparative studies written in English or in French, published from January 2000 to April 2015. We collected the literature data on HCV-infected patients concerning the prevalence of glucose abnormalities [diabetes mellitus (DM) and insulin resistance (IR)] and associated risk [i.e., severe liver fibrosis, response to antivirals, and the occurrence of hepatocellular carcinoma (HCC)].
RESULTS HCV infection is significantly associated with DM/IR compared with healthy volunteers and patients with hepatitis B virus infection. Glucose abnormalities were associated with advanced liver fibrosis, lack of sustained virologic response to interferon alfa-based treatment and with a higher risk of HCC development. As new antiviral therapies may offer a cure for HCV infection, such data should be taken into account, from a therapeutic and preventive point of view, for liver and non-liver consequences of HCV disease. The efficacy of antidiabetic treatment in improving the response to antiviral treatment and in decreasing the risk of HCC has been reported by some studies but not by others. Thus, the effects of glucose abnormalities correction in reducing liver events need further studies.
CONCLUSION Glucose abnormalities are strongly associated with HCV infection and show a negative impact on the main liver related outcomes.
Collapse
|
|
36
|
Hepatitis C virus and atherosclerosis: A legacy after virologic cure? Clin Res Hepatol Gastroenterol 2017; 41:25-30. [PMID: 27840032 DOI: 10.1016/j.clinre.2016.09.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Revised: 09/14/2016] [Accepted: 09/22/2016] [Indexed: 02/07/2023]
Abstract
Hepatitis C virus (HCV) is a major pathogen with approximately 3% of the world's population (over 170 million) infected. Epidemiological studies have shown HCV is associated with an increased risk of cardiovascular and cerebrovascular mortality as well as peripheral arterial disease. This is despite HCV inducing an ostensibly favourable lipid profile with accompanying low classical risk score for atherosclerosis (AS). We discuss possible factors involved in the aetiopathogenesis of atherosclerosis in chronic HCV and hypothesise that an important mechanism underlying the development of AS is the presence of circulating low-density immune complexes that induce an inflammatory response. We suggest that HCV particles may be inducing an antibody response to lipoproteins present in the lipoviral particles and sub-viral particles - a concept similar to the more general 'autoantibody' response to modified LDL. After virologic cure some AS risk factors will recede but an increase in serum cholesterol could result in progression of early atherosclerotic lesions, leaving a legacy from persistent HCV infection that has clinical and therapeutic implications.
Collapse
|
|
37
|
Yan W, Song Y, Zhou L, Jiang J, Yang F, Duan Q, Che L, Shen Y, Song H, Wang L. Immune Cell Repertoire and Their Mediators in Patients with Acute Myocardial Infarction or Stable Angina Pectoris. Int J Med Sci 2017; 14:181-190. [PMID: 28260995 PMCID: PMC5332848 DOI: 10.7150/ijms.17119] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Accepted: 12/21/2016] [Indexed: 12/14/2022] Open
Abstract
Background: To evaluate the natural innate and adaptive immunity through gene expression and cytology levels in peripheral blood mononuclear cells in patients with acute myocardial infarction (AMI), stable angina pectoris (SAP) and controls. Methods: 210 patients with AMI, 210 with SAP, and 250 clinical controls were recruited. Whole human genome microarray analysis was performed in 20 randomly chosen subjects per group were examined to detect the expressions of complement markers, natural killer cells, T cells and B cells. The quantity of these cells and related cytokines as well as immunoglobulin levels were measured in all subjects. Results: In AMI group, the mRNA expressions of late complement component, markers of natural killer cells, CD3+, CD8+ T cells and B cells were down-regulated, while those of early complement component and CD4+T cells were up-regulated (p<0.05). In both AMI and SAP patients, the quantity of natural killer cells, CD3+, CD8+ T cells, B cells, IgM and IgG were significantly lower than those of the controls. CD4+ T cells, CH50, C3, C4, IL-2, IL-4, IL-6 and IFN-γ were significantly higher (p<0.05). Conclusions: In AMI patients, both of gene expressions related to complement, natural killer cells, CD3+, CD8+ T cells, B cells and the quantity of these immune cells decreased while cell number reduced in SAP patients. Immune function in both AMI and SAP patients decreased especially in AMI patients with declined gene and protein levels. To improve the immune system is a potential target for medical interventions and prevention in AMI.
Collapse
Affiliation(s)
- Wenwen Yan
- Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Yanli Song
- Department of Emergency Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Lin Zhou
- Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Jinfa Jiang
- Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Fang Yang
- Department of Experimental Diagnosis, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Qianglin Duan
- Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Lin Che
- Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Yuqin Shen
- Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Haoming Song
- Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Lemin Wang
- Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| |
Collapse
|
|
38
|
Lonardo A, Ballestri S, Guaraldi G, Nascimbeni F, Romagnoli D, Zona S, Targher G. Fatty liver is associated with an increased risk of diabetes and cardiovascular disease - Evidence from three different disease models: NAFLD, HCV and HIV. World J Gastroenterol 2016; 22:9674-9693. [PMID: 27956792 PMCID: PMC5124973 DOI: 10.3748/wjg.v22.i44.9674] [Citation(s) in RCA: 91] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Revised: 09/29/2016] [Accepted: 10/31/2016] [Indexed: 02/06/2023] Open
Abstract
Fatty liver, which frequently coexists with necro-inflammatory and fibrotic changes, may occur in the setting of nonalcoholic fatty liver disease (NAFLD) and chronic infections due to either hepatitis C virus (HCV) or human immunodeficiency virus (HIV). These three pathologic conditions are associated with an increased prevalence and incidence of cardiovascular disease (CVD) and type 2 diabetes (T2D). In this multidisciplinary clinical review, we aim to discuss the ever-expanding wealth of clinical and epidemiological evidence supporting a key role of fatty liver in the development of T2D and CVD in patients with NAFLD and in those with HCV or HIV infections. For each of these three common diseases, the epidemiological features, pathophysiologic mechanisms and clinical implications of the presence of fatty liver in predicting the risk of incident T2D and CVD are examined in depth. Collectively, the data discussed in this updated review, which follows an innovative comparative approach, further reinforce the conclusion that the presence of fatty/inflamed/fibrotic liver might be a shared important determinant for the development of T2D and CVD in patients with NAFLD, HCV or HIV. This review may also open new avenues in the clinical and research arenas and paves the way for the planning of future, well-designed prospective and intervention studies.
Collapse
|
|
39
|
Chang CY, Lin SY, Tsai JR, Tsai CH, Chen YC. Successful multivessel percutaneous coronary intervention for acute coronary syndrome in a HIV-positive severe haemophiliac. Haemophilia 2016; 22:e481-4. [PMID: 27501528 DOI: 10.1111/hae.13056] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/27/2016] [Indexed: 12/14/2022]
Affiliation(s)
- C-Y Chang
- School of Medicine, Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.,Hemophilia Center, Division of Pediatric Hematology/Oncology, Department of Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan
| | - S-Y Lin
- School of Medicine, Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.,Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - J-R Tsai
- School of Medicine, Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.,Department of Hematology/Oncology, Taipei Medical University Hospital, Taipei, Taiwan
| | - C-H Tsai
- School of Medicine, Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.,Department of Hematology/Oncology, Cheng Hsin General Hospital, Taipei, Taiwan
| | - Y-C Chen
- Division of Hematology/Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. .,Hemophilia Care and Research Center, Tri-Service General Hospital, Taipei, Taiwan.
| |
Collapse
|
|
40
|
Petta S. Hepatitis C virus and cardiovascular: A review. J Adv Res 2016; 8:161-168. [PMID: 28149651 PMCID: PMC5272956 DOI: 10.1016/j.jare.2016.06.001] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2016] [Revised: 06/05/2016] [Accepted: 06/11/2016] [Indexed: 02/07/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection is a systemic disease that leads to increased risks of cirrhosis and its complications, as well as extrahepatic disturbances, including immune-related disorders and metabolic alterations such as insulin resistance and steatosis. Recent accumulating evidence suggests that HCV infection can increase cardiovascular risk, and that viral eradication can improve cardiovascular outcomes in the clinical setting. These data are strengthened by evidence identifying potential mechanisms (in)directly linking HCV infection to vascular damage. However, the high prevalence of both HCV infection and cardiovascular alterations, as well as the presence of contrasting results not identifying any association between HCV infection and cardiovascular dysfunction, provides uncertainty about a direct association of HCV infection with cardiovascular risk. Further studies are needed to clarify definitively the role of HCV infection in cardiovascular alterations, as well as the impact of viral eradication on cardiovascular outcomes. These features are now more attractive, considering the availability of new, safe, and very effective interferon-free antiviral agents for the treatment of HCV infection. This review aims to discuss carefully available data on the relationship between HCV infection and cardiovascular risk.
Collapse
Affiliation(s)
- Salvatore Petta
- Sezione di Gastroenterologia, Dipartimento Biomedico di Medicina Interna e Specialistica, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| |
Collapse
|
|
41
|
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.
Collapse
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.
| |
Collapse
|
|
42
|
Domont F, Cacoub P. Chronic hepatitis C virus infection, a new cardiovascular risk factor? Liver Int 2016; 36:621-7. [PMID: 26763484 DOI: 10.1111/liv.13064] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Accepted: 12/31/2015] [Indexed: 12/13/2022]
Abstract
Among the large scope of extrahepatic manifestations related to hepatitis C virus (HCV) infection, many studies recently evaluated the frequency and characteristics of cardiovascular involvement. To assess the current published data on HCV infection and cardiovascular diseases. Published studies on cardiovascular disease, i.e. cerebrovascular accident and ischaemic heart disease in subjects with HCV infection were analysed from literature databases. Subjects with HCV chronic infection have an increased prevalence of carotid atherosclerosis and increased intima-media thickness compared to healthy controls or those with hepatitis B or non-alcoholic steatohepatitis. Active chronic HCV infection appears as an independent risk factor for ischaemic cerebrovascular accidents. Active chronic HCV infection is associated with increased risk of ischaemic heart disease. In some studies, successful interferon-based therapy showed a beneficial impact on the cardiovascular risk. The risk of major cardiovascular events is higher in patients with HCV infection compared to controls, independent of the severity of the liver disease or the common cardiovascular risk factors. The beneficial impact of interferon-based therapy needs to be confirmed with new direct antiviral interferon-free agents in prospective studies with extended follow-up.
Collapse
Affiliation(s)
- Fanny Domont
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, Paris, France.,Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France.,Department of Internal Medicine and Clinical Immunology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
| | - Patrice Cacoub
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, Paris, France.,Department of Internal Medicine and Clinical Immunology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.,INSERM, UMR-S 959, Paris, France.,CNRS, FRE3632, Paris, France
| |
Collapse
|
|
43
|
Hu JH, Chen MY, Yeh CT, Lin HS, Lin MS, Huang TJ, Chang ML. Sexual Dimorphic Metabolic Alterations in Hepatitis C Virus-infected Patients: A Community-Based Study in a Hepatitis B/Hepatitis C Virus Hyperendemic Area. Medicine (Baltimore) 2016; 95:e3546. [PMID: 27149466 PMCID: PMC4863783 DOI: 10.1097/md.0000000000003546] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
The impact of sex on metabolic alterations in individuals with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection remains elusive.A community-based study was performed to assess sex, age, body mass index, the lipid profile, blood pressure, glucose, alanine aminotransferase, HBV surface antigen (HBsAg), and HCV antibody levels, smoking and alcohol drinking habits, and cardiometabolic diseases, including diabetes, hypertension, cardiovascular events, and renal diseases. The HCV-RNA level and genotype were further assessed in HCV antibody-positive subjects, and the hepatitis B e antigen and HBV-DNA levels were further examined in HBsAg-positive subjects.Among the 10,959 adults enrolled, 1949 (17.8%) and 1536 (14.0%) were HBV and HCV-infected, respectively. Univariate and multivariate analyses showed that the lipid profile and hypertension were independently associated with HCV infection (95% confidence intervals of odds ratios [OR 95% CI]: total cholesterol [TC] = 0.508-0.677; triglycerides = 0.496-0.728; hypertension = 0.669-0.937), but not with HBV infection. Consistently, HCV, but not HBV infection, was negatively associated with the TC and triglyceride levels (OR 95% CI for TC: 0.450-0.601; triglycerides: 0.443-0.671). Generalized linear models revealed that HCV infection, sex, and age interactively affected the lipid profile (OR 95% CI TC = 1.189-1.385; triglycerides = 1.172-5.289). Age-stratification analysis showed that the lipid levels were lower in both the HCV-positive females aged ≥49 years (TC, P < 0.001; triglycerides, P = 0.001) and males of all ages (TC, P < 0.001; triglycerides, P < 0.001) compared with their sex and age-matched HCV-negative counterparts. HCV infection was associated with a higher body mass index (≥49 years, β = 0.405, P = 0.002) and increased rates of cardiovascular events (<49 years, OR 95% CI 1.23-9.566), diabetes (≥49 years, OR 95% CI 1.114-1.932), and renal diseases (≥49 years, OR 95% CI 1.23-9.55), and with a lower rate of hypertension (≥49 years, OR 95% CI 0.616-0.964) in the females, but not in the males, as determined by multivariate analyses.Only HCV infection was associated with metabolic alterations in this HBV/HCV-hyperendemic area. Females aged ≥49 years and males of all ages exhibited HCV-associated hypolipidemia. HCV-associated cardiometabolic diseases were evident only in the females. Sex dimorphism in HCV-associated metabolic complications warrants personalized follow-up of HCV-positive patients.
Collapse
Affiliation(s)
- Jing-Hong Hu
- From the Department of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Yunlin, Taiwan (J-HH); College of Nursing, Chang Gung University of Science and Technology, Putz City, Chiayi County, Taiwan (M-YC); Liver Research Center and Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taiwan (C-TY, M-LC); Division of Infection Disease, Department of Medicine, Chang Gung Memory Hospital, Chia-yi, Taiwan (H-SL); Division of Cardiology, Chang-Gung Memorial Hospital, Yunlin, Taiwan (M-SL); Division of Thoracic Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital, Yunlin, Taiwan (T-JH); and Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, (M-LC)
| | | | | | | | | | | | | |
Collapse
|
|
44
|
Ballestri S, Nascimbeni F, Romagnoli D, Baldelli E, Targher G, Lonardo A. Type 2 Diabetes in Non-Alcoholic Fatty Liver Disease and Hepatitis C Virus Infection--Liver: The "Musketeer" in the Spotlight. Int J Mol Sci 2016; 17:355. [PMID: 27005620 PMCID: PMC4813216 DOI: 10.3390/ijms17030355] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Revised: 02/29/2016] [Accepted: 03/02/2016] [Indexed: 02/07/2023] Open
Abstract
The pathogenesis of type 2 diabetes (T2D) involves chronic hyperinsulinemia due to systemic and hepatic insulin resistance (IR), which if uncorrected, will lead to progressive pancreatic beta cell failure in predisposed individuals. Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of fatty (simple steatosis and steatohepatitis) and non-fatty liver changes (NASH-cirrhosis with or without hepatocellular carcinoma (HCC)) that are commonly observed among individuals with multiple metabolic derangements, notably including visceral obesity, IR and T2D. Hepatitis C virus (HCV) infection is also often associated with both hepatic steatosis and features of a specific HCV-associated dysmetabolic syndrome. In recent years, the key role of the steatotic liver in the development of IR and T2D has been increasingly recognized. Thus, in this comprehensive review we summarize the rapidly expanding body of evidence that links T2D with NAFLD and HCV infection. For each of these two liver diseases with systemic manifestations, we discuss the epidemiological burden, the pathophysiologic mechanisms and the clinical implications. To date, substantial evidence suggests that NAFLD and HCV play a key role in T2D development and that the interaction of T2D with liver disease may result in a "vicious circle", eventually leading to an increased risk of all-cause mortality and liver-related and cardiovascular complications. Preliminary evidence also suggests that improvement of NAFLD is associated with a decreased incidence of T2D. Similarly, the prevention of T2D following HCV eradication in the era of direct-acting antiviral agents is a biologically plausible result. However, additional studies are required for further clarification of mechanisms involved.
Collapse
Affiliation(s)
- Stefano Ballestri
- Operating Unit Internal Medicine, Pavullo General Hospital, Azienda USL Modena, ViaSuore di San Giuseppe Benedetto Cottolengo, 5, Pavullo, 41026 Modena, Italy.
| | - Fabio Nascimbeni
- Outpatient Liver Clinic and Operating Unit Internal Medicine, NOCSAE, Azienda USL Modena, Via P. Giardini, 1355, 41126 Modena, Italy.
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via P. Giardini, 1355, 41126 Modena, Italy.
| | - Dante Romagnoli
- Outpatient Liver Clinic and Operating Unit Internal Medicine, NOCSAE, Azienda USL Modena, Via P. Giardini, 1355, 41126 Modena, Italy.
| | - Enrica Baldelli
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via P. Giardini, 1355, 41126 Modena, Italy.
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale Stefani, 1, 37126 Verona, Italy.
| | - Amedeo Lonardo
- Outpatient Liver Clinic and Operating Unit Internal Medicine, NOCSAE, Azienda USL Modena, Via P. Giardini, 1355, 41126 Modena, Italy.
| |
Collapse
|
|
45
|
Vanni E, Bugianesi E, Saracco G. Treatment of type 2 diabetes mellitus by viral eradication in chronic hepatitis C: Myth or reality? Dig Liver Dis 2016; 48:105-11. [PMID: 26614641 DOI: 10.1016/j.dld.2015.10.016] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2015] [Revised: 10/05/2015] [Accepted: 10/16/2015] [Indexed: 12/15/2022]
Abstract
Chronic hepatitis C is a systemic disease inducing metabolic alterations leading to extrahepatic consequences. In particular, hepatitis C virus (HCV) infection seems to increase the risk of incident type 2 diabetes mellitus in predisposed individuals, independently of liver disease stage. The mechanisms through which hepatitis C induces T2DM involve direct viral effects, insulin resistance, pro-inflammatory cytokines and other immune-mediated processes. Many studies have reported the clinical consequences of type 2 diabetes mellitus on hepatitis C outcome, but very few studies have addressed the issue of microangiopathic complications among patients with hepatitis C only, who develop type 2 diabetes mellitus. Moreover, clinical trials in HCV-positive patients have reported improvement in glucose metabolism after antiviral treatment; recent studies have suggested that this metabolic amelioration might have a clinical impact on type 2 diabetes mellitus-related complications. These observations raise the question as to whether the HCV eradication may also have an impact on the future morbidity and mortality due to type 2 diabetes mellitus. The scope of this review is to summarise the current evidence linking successful antiviral treatment and the prevention of type 2 diabetes mellitus and its complications in hepatitis C-infected patients.
Collapse
Affiliation(s)
- Ester Vanni
- Gastro-hepatology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Elisabetta Bugianesi
- Gastro-hepatology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Giorgio Saracco
- Gastroenterology Unit, Oncology Department, University of Turin, Italy.
| |
Collapse
|
|
46
|
Chang ML. Metabolic alterations and hepatitis C: From bench to bedside. World J Gastroenterol 2016; 22:1461-1476. [PMID: 26819514 PMCID: PMC4721980 DOI: 10.3748/wjg.v22.i4.1461] [Citation(s) in RCA: 93] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2015] [Revised: 08/14/2015] [Accepted: 10/26/2015] [Indexed: 02/06/2023] Open
Abstract
In addition to causing cirrhosis and hepatocellular carcinoma, hepatitis C virus (HCV) is thought to cause hypolipidemia, hepatic steatosis, insulin resistance, metabolic syndrome, and diabetes. The viral life cycle of HCV depends on cholesterol metabolism in host cells. HCV core protein and nonstructural protein 5A perturb crucial lipid and glucose pathways, such as the sterol regulatory element-binding protein pathway and the protein kinase B/mammalian target of rapamycin/S6 kinase 1 pathway. Although several lines of transgenic mice expressing core or full HCV proteins exhibit hepatic steatosis and/or dyslipidemia, whether they completely reflect the metabolic alterations in humans with HCV infection remains unknown. Many cross-sectional studies have demonstrated increased prevalences of metabolic alterations and cardiovascular events in patients with chronic hepatitis C (CHC); however, conflicting results exist, primarily due to unavoidable individual variations. Utilizing anti-HCV therapy, most longitudinal cohort studies of CHC patients have demonstrated the favorable effects of viral clearance in attenuating metabolic alterations and cardiovascular risks. To determine the risks of HCV-associated metabolic alterations and associated complications in patients with CHC, it is necessary to adjust for crucial confounders, such as HCV genotype and host baseline glucose metabolism, for a long follow-up period after anti-HCV treatment. Adipose tissue is an important endocrine organ due to its release of adipocytokines, which regulate lipid and glucose metabolism. However, most data on HCV infection and adipocytokine alteration are inconclusive. A comprehensive overview of HCV-associated metabolic and adipocytokine alterations, from bench to bedside, is presented in this topic highlight.
Collapse
|
|
47
|
Atherosclerosis as Extrahepatic Manifestation of Chronic Infection with Hepatitis C Virus. HEPATITIS RESEARCH AND TREATMENT 2016; 2016:7629318. [PMID: 26885388 PMCID: PMC4738722 DOI: 10.1155/2016/7629318] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/11/2015] [Accepted: 12/20/2015] [Indexed: 12/11/2022]
Abstract
Chronic hepatitis C virus infection is associated with significant morbidity and mortality, as a result of progression towards advanced natural course stages including cirrhosis and hepatocellular carcinoma. On the other hand, the SVR following successful therapy is generally associated with resolution of liver disease in patients without cirrhosis. Patients with cirrhosis remain at risk of life-threatening complications despite the fact that hepatic fibrosis may regress and the risk of complications such as hepatic failure and portal hypertension is reduced. Furthermore, recent data suggest that the risk of HCC and all-cause mortality is significantly reduced, but not eliminated, in cirrhotic patients who clear HCV compared to untreated patients and nonsustained virological responders. Data derived from studies have demonstrated a strong link between HCV infection and the atherogenic process. Subsequently HCV seems to represent a strong, independent risk factor for coronary heart disease, carotid atherosclerosis, stroke, and, ultimately, CVD related mortality. 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 which may influence the life expectancy and the quality of patients' life.
Collapse
|
|
48
|
Petta S, Maida M, Macaluso FS, Barbara M, Licata A, Craxì A, Cammà C. Hepatitis C Virus Infection Is Associated With Increased Cardiovascular Mortality: A Meta-Analysis of Observational Studies. Gastroenterology 2016; 150:145-155.e4; quiz e15-6. [PMID: 26386298 DOI: 10.1053/j.gastro.2015.09.007] [Citation(s) in RCA: 187] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Revised: 08/11/2015] [Accepted: 09/03/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS There have been many studies of the effects of hepatitis C virus (HCV) infection on cardiovascular risk, but these have produced ambiguous results. We performed a meta-analysis of these studies to systematically assess the risk of HCV infection on cardiovascular disease (CVD)-related morbidity and mortality. METHODS We searched PubMed Central, Medline, Embase, and Cochrane Library, as well as reference lists of articles, for studies published through July 2015 that compared the occurrence of CVD between HCV-infected and HCV-uninfected subjects, or assessed the prevalence of HCV infection among subjects with CVDs. In total, 22 studies were analyzed. Data on the patient populations and outcomes were extracted from each study by 3 independent observers and combined by a random-effects model. RESULTS Compared with uninfected individuals (controls), HCV-infected patients had increased risks of CVD-related mortality (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.07-2.56; P = .02), carotid plaques (OR, 2.27; 95% CI, 1.76-2.94; P < .001), and cerebrocardiovascular events (OR, 1.30; 95% CI, 1.10-1.55; P = .002). Significant heterogeneity was observed in the risk of cerebrocardiovascular disease among individuals with HCV infection. The effect of HCV infection on cerebrocardiovascular disease was stronger in populations with a higher prevalence of diabetes (>10%) or hypertension (>20%) (OR, 1.71; 95% CI, 1.32-2.23; P < .001 for both). CONCLUSIONS In a meta-analysis of published studies, individuals with HCV infections were found to be at increased risk for CVD-related morbidity and mortality-especially patients with diabetes and hypertension.
Collapse
Affiliation(s)
- Salvatore Petta
- Sezione di Gastroenterologia, Dipartimento Biomedico di Medicina Interna e Specialistica, Università di Palermo, Palermo, Italy.
| | - Marcello Maida
- Sezione di Gastroenterologia, Dipartimento Biomedico di Medicina Interna e Specialistica, Università di Palermo, Palermo, Italy
| | - Fabio Salvatore Macaluso
- Sezione di Gastroenterologia, Dipartimento Biomedico di Medicina Interna e Specialistica, Università di Palermo, Palermo, Italy
| | - Marco Barbara
- Sezione di Gastroenterologia, Dipartimento Biomedico di Medicina Interna e Specialistica, Università di Palermo, Palermo, Italy
| | - Anna Licata
- Sezione di Gastroenterologia, Dipartimento Biomedico di Medicina Interna e Specialistica, Università di Palermo, Palermo, Italy
| | - Antonio Craxì
- Sezione di Gastroenterologia, Dipartimento Biomedico di Medicina Interna e Specialistica, Università di Palermo, Palermo, Italy
| | - Calogero Cammà
- Sezione di Gastroenterologia, Dipartimento Biomedico di Medicina Interna e Specialistica, Università di Palermo, Palermo, Italy
| |
Collapse
|
|
49
|
Ciccone MM, Principi M, Ierardi E, Di Leo A, Ricci G, Carbonara S, Gesualdo M, Devito F, Zito A, Cortese F, Scicchitano P. Inflammatory bowel disease, liver diseases and endothelial function: is there a linkage? J Cardiovasc Med (Hagerstown) 2015; 16:11-21. [PMID: 25427048 DOI: 10.2459/jcm.0000000000000149] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Atherosclerosis is a systemic inflammatory disease able to deeply worsen the outcome of patients because of its serious clinical consequences. The complex inflammatory background underlining such a disease makes atherosclerosis linked to several systemic inflammatory conditions able to impair endothelial function and morphology. Inflammatory bowel diseases are a group of gastrointestinal diseases including Crohn's disease and ulcerative colitis, that is, syndromes characterized by changes in mucosal immunity and gastrointestinal physiology, which could negatively influence the vascular endothelial function and structure. Hepatitis (i.e. inflammatory diseases of the liver mainly due to viral infections) and nonalcoholic fatty liver disease could be aligned to inflammatory bowel disease in such an induction of atherosclerosis disease.Many studies tried to point out the relationship between bowel and liver inflammatory diseases and early vascular changes, considered the first step for atherosclerosis development.The aim of such a narrative review is to explain the relationship between inflammatory bowel disease, hepatitis and nonalcoholic fatty liver disease and their role in increasing cardiovascular risk profile due to early impairment in vascular function and morphology.
Collapse
Affiliation(s)
- Marco Matteo Ciccone
- aDepartment of Emergency and Organ Transplantation (DETO) bUniversity of Bari, Bari cDepartment of Medical Sciences, Section of Gastroenterology, University of Foggia, Foggia, Italy
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
50
|
Kukla M, Piotrowski D, Waluga M, Hartleb M. Insulin resistance and its consequences in chronic hepatitis C. Clin Exp Hepatol 2015; 1:17-29. [PMID: 28856251 PMCID: PMC5421163 DOI: 10.5114/ceh.2015.51375] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2015] [Accepted: 03/10/2015] [Indexed: 02/07/2023] Open
Abstract
Chronic hepatitis C (CHC) is generally a slowly progressive disease, but some factors associated with rapid progression have been identified. Hepatitis C virus (HCV) may contribute to a broad spectrum of metabolic disturbances - namely, steatosis, insulin resistance (IR), increased prevalence of impaired glucose tolerance, type 2 diabetes mellitus (T2DM), lipid metabolism abnormalities and atherosclerosis. HCV can directly or indirectly cause both IR and steatosis, but it is still not resolved whether this viral impact bears the same prognostic value as the metabolic counterparts. As the population exposed to HCV ages, the morbidity due to this disease is increasing. The rising epidemic of obesity contributes to higher prevalence of IR and T2DM. Our understanding of the mutual association between both disease states continues to grow, but is still far from complete. This review briefly discusses the most probable mechanisms involved in IR development in the course of CHC. Molecular mechanisms for the direct and indirect influence of HCV on intracellular insulin signaling are described. Subsequently, the consequences of IR/T2DM for disease progression and management are summarized.
Collapse
Affiliation(s)
- Michał Kukla
- Department of Gastroenterology and Hepatology, Medical University of Silesia in Katowice, Poland
| | - Damian Piotrowski
- Department of Infectious Diseases in Bytom, Medical University of Silesia in Katowice, Poland
| | - Marek Waluga
- Department of Gastroenterology and Hepatology, Medical University of Silesia in Katowice, Poland
| | - Marek Hartleb
- Department of Gastroenterology and Hepatology, Medical University of Silesia in Katowice, Poland
| |
Collapse
|