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Brzdęk M, Gałuszka-Garnuszek J, Dobrowolska K, Brzdęk K, Janczura J, Tronina O, Kal M, Stępień P, Zarębska-Michaluk D. Oral manifestations in patients with chronic hepatitis C. BMC Oral Health 2025; 25:944. [PMID: 40490688 DOI: 10.1186/s12903-025-06307-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2025] [Accepted: 05/29/2025] [Indexed: 06/11/2025] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) infection, a systemic disease characterized by extrahepatic manifestations (EMs), affects approximately 50 million people worldwide. Recognizing EMs, which may involve multiple organs and systems, is crucial for timely diagnosis and effective antiviral therapy. Purpose of the study was to investigate extrahepatic symptoms occurring in the oral mucosa in HCV-infected patients. METHODS The observational study included 153 consecutive patients with chronic hepatitis C and healthy controls. Data collection encompassed demographic parameters, medical history, laboratory results, and oral examinations, which included evaluation of dry mouth, pain and burning in the mouth and on the tongue, pain in the angles of the mouth, bad breath, gingival bleeding, dysphagia and taste disorders using scales designed for this purpose, clinical and dental examination. RESULTS Subjective oral symptoms were twice as common in the study group as in controls with the most frequent dry mouth, followed by oral pain, and burning in the mouth. Pathological changes (oral candidiasis, angular cheilitis and lichen planus), were identified in 73.2% of patients, compared to 32% in the control group. Oral hygiene was worse in the study group with a median score of 1.8 compared to 1.1 as assessed by the Oral Hygiene Index scale. The incidence of Mikulicz's aphthae, papillomas, fibromas and sublingual varices did not reach statistically significant differences. The study group had fewer teeth with dental fillings. Additionally, age ≥ 40 years and GT1 infection were identified as independent predictors of oral pathologies in HCV-infected patients. CONCLUSIONS In patients with chronic HCV infection, oral mucosal pathologies were significantly more common compared to controls, with candidiasis, angular cheilitis, and oral lichen planus being the most frequently observed conditions. Subjective symptoms such as dry mouth, oral pain, and burning were also markedly higher in the HCV group. Age ≥ 40 years and GT1b HCV genotype were identified as independent positive predictors of oral mucosal lesions.
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Affiliation(s)
- Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland
- Department of Gastroenterology, Medical University of Lodz, Lodz, Poland
| | | | | | - Kinga Brzdęk
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland.
| | - Jakub Janczura
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland
| | - Olga Tronina
- Department of Transplant Medicine, Immunology, Nephrology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Magdalena Kal
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland
- Ophthalmic Clinic of the Voivodeship Hospital in Kielce, Kielce, Poland
| | - Piotr Stępień
- Department of Infectious Diseases and Allergology, Jan Kochanowski University, Kielce, Poland
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Yang F, Luo J. The association between hepatitis C virus infection status and blood pressure in adults in the United States: NHANES 1999-2012. Front Cell Infect Microbiol 2024; 14:1401323. [PMID: 38895738 PMCID: PMC11183278 DOI: 10.3389/fcimb.2024.1401323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 05/22/2024] [Indexed: 06/21/2024] Open
Abstract
Background The Hepatitis C virus (HCV) infection is strongly associated with cardiovascular disease risk factors, but the relationship with blood pressure (BP) remains unclear. Objectives To assess the association between HCV infection status and BP in US adults. Methods Data for the study were obtained from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2012. The association of HCV infection status (including HCV infection, current HCV infection, and past HCV infection) with hypertension, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were explored using logistic or linear regression analyses respectively. Results A total of 25,850 participants (age≥18 years) were enrolled in the current study, including 14,162 participants with hypertension. After adjusting for all covariates, HCV infection/current HCV infection was not associated with hypertension and SBP compared to participants with non-HCV infection (OR: 1.34,95% CI 0.96-1.87/1.31 95% CI 0.91,1.91, β: -0.92, 95% CI -2.7-0.86/-0.35 95% CI -2.51,1.81, respectively). HCV infection/current HCV infection was only associated with elevated DBP (β: 4.1,95% CI 2.57-5.63/4.24,95% CI 2.27-6.21). However, there was no correlation with past HCV infection in participants with hypertension, SBP, and DBP compared to those with non-HCV infection (OR: 1.23,95% CI 0.59-2.54; β: -3.79, 95% CI -7.67-0.08 and 2.28 95% CI -0.36-4.92, respectively). Conclusion In a representative sample of US adults, it was found that both HCV infection and current HCV infection were independently linked to higher DBP. However, there was no association between past HCV infection and DBP.
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Affiliation(s)
| | - Jianping Luo
- Department of Cardiology, Ganzhou People’s Hospital, Ganzhou, Jiangxi, China
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Yang L, Lu Z, Bian J, Li F, Zou H. Association between chronic viral infection-related hospitalization and risk of cardiovascular disease: A population-based cohort study. J Med Virol 2024; 96:e29350. [PMID: 38180233 DOI: 10.1002/jmv.29350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 12/12/2023] [Accepted: 12/15/2023] [Indexed: 01/06/2024]
Abstract
Chronic viral infection induces immunosenescence and systemic low-grade inflammation, leading to worsened long-term outcomes. We sought to explore the short- and long-term effects of chronic viral infection on cardiovascular disease (CVD). Based on UK Biobank data, exposed group was identified as individuals who had chronic virus infection-related hospitalization (IRH). Unexposed group was randomly selected, matched by 5-year age interval, sex, and Charlson comorbidity index at a ratio up to 1:10. Restricted cubic splines were used to model time-varying effects of IRH in nonproportional Cox models. A cut-off value of 5 years was recorded and used in piecewise Cox proportional hazards models as we estimated short- and long-term effects of IRH on CVD. A total of 2826 exposed participants and 28 212 matched unexposed participants were included. Chronic viral IRH was associated with increased risk of CVD (0-5 years: hazard ratio, 1.57 [95% confidence interval: 1.32, 1.87] and 5+ years: 1.31 [1.06, 1.61]). Elevated risk of stroke was only observed within the initial 5-year follow-up (0-5 years: 1.91 [1.30, 2.81]). The short- and long-term associations were observed in herpes or hepatitis virus IRH with risk of CVD (all p < 0.05). Subgroup analysis revealed long-term association between chronic viral IRH and CVD among female (5+ years: 1.68 [1.27, 2.22]) but not among male. The association between chronic viral infection and elevated CVD risk appeared to be stronger among individuals who did not take cholesterol-lowering medication, antithrombotic medication, or certain antihypertensive medications (all p for interaction < 0.05). The risk of CVD event remained persistently higher within and over 5 years following chronic viral IRH, especially in individuals infected with herpes and hepatitis virus.
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Affiliation(s)
- Luoyao Yang
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, People's Republic of China
| | - Zhen Lu
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, People's Republic of China
| | - Junye Bian
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, People's Republic of China
| | - Feng Li
- Department of Cardiac and Vascular Surgery, The 1st Affiliated Hospital of AnHui Medical University, Hefei, China
| | - Huachun Zou
- School of Public Health, Fudan University, Shanghai, China
- School of Public Health, Southwest Medical University, Luzhou, China
- Kirby Institute, University of New South Wales, Sydney, Australia
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Neokosmidis G, Protopapas AA, Stogiannou D, Filippidis A, Tziomalos K. Cardiometabolic effects of direct-acting antivirals in patients with hepatitis C. GASTROENTEROLOGIA Y HEPATOLOGIA 2023; 46:58-66. [PMID: 35460863 DOI: 10.1016/j.gastrohep.2022.03.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 03/08/2022] [Indexed: 01/18/2023]
Abstract
Hepatitis C virus (HCV) has long been associated with several extrahepatic manifestations, including increased cardiovascular risk. The emergence of direct-acting antivirals (DAAs) has allowed us to evaluate the potential reversal of these manifestations after successful treatment. Therefore, many studies have provided significant takeaways regarding the positive effect of DAAs therapy on insulin resistance, type 2 diabetes mellitus, cardiovascular disease and atherosclerosis. In contrast, studies have shown detrimental effects on lipid metabolism and indeterminate results regarding renal function and uric acid metabolism. Nevertheless, as more and more patients achieve sustained virological response, the effects of HCV eradication on cardiometabolic processes will be extensively studied, allowing more reliable conclusions on the extent of extrahepatic outcomes.
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Affiliation(s)
- Georgios Neokosmidis
- First Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| | - Adonis A Protopapas
- First Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece.
| | - Dimitrios Stogiannou
- First Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| | - Athanasios Filippidis
- First Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| | - Konstantinos Tziomalos
- First Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
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Beydoun N, Feinstein MJ. Heart Failure in Chronic Infectious and Inflammatory Conditions: Mechanistic Insights from Clinical Heterogeneity. Curr Heart Fail Rep 2022; 19:267-278. [PMID: 35838874 PMCID: PMC9283814 DOI: 10.1007/s11897-022-00560-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/29/2022] [Indexed: 01/21/2023]
Abstract
PURPOSE OF REVIEW The balance between inflammation and its resolution plays an important and increasingly appreciated role in heart failure (HF) pathogenesis. In humans, different chronic inflammatory conditions and immune-inflammatory responses to infection can lead to diverse HF manifestations. Reviewing the phenotypic and mechanistic diversity of these HF presentations offers useful clinical and scientific insights. RECENT FINDINGS HF risk is increased in patients with chronic inflammatory and autoimmune disorders and relates to disease severity. Inflammatory condition-specific HF manifestations exist and underlying pathophysiologic causes may differ across conditions. Although inflammatory disease-specific presentations of HF differ, chronic excess in inflammation and auto-inflammation relative to resolution of this inflammation is a common underlying contributor to HF. Further studies are needed to phenotypically refine inflammatory condition-specific HF pathophysiologies and prognoses, as well as potential targets for intervention.
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Affiliation(s)
- Nour Beydoun
- Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Matthew J Feinstein
- Division of Cardiology, Department of Medicine, Northwestern University, Chicago, IL, USA.
- Department of Pathology, Northwestern University, Chicago, IL, USA.
- Department of Preventive Medicine, Northwestern University, Chicago, IL, USA.
- Northwestern University Feinberg School of Medicine, 300 E. Superior St, Tarry 3-703, Chicago, IL, 60611, USA.
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Wang CH, Ou SF, Tseng YT. Long-term impact of certain coexisting extrahepatic unisystem and multisystem manifestations on trends in incidence of liver cirrhosis in treatment-naïve patients with chronic hepatitis C: A nested case-control study. Medicine (Baltimore) 2022; 101:e29697. [PMID: 35866797 PMCID: PMC9302331 DOI: 10.1097/md.0000000000029697] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Diabetes mellitus (DM) was found to be more common in hepatitis C virus (HCV)-related cirrhotic males. However, the association between DM, or other extrahepatic manifestations (EHMs), and liver cirrhosis is still undetermined. We used a large-scale long-term study to analyze the cirrhosis risk of treatment-naïve HCV patients with EHMs as compared to those without. In this retrospective nested case-control study, we identified 11 872 treatment-naïve patients with chronic HCV between 2001 and 2013 from Taiwan National Health Insurance Research Database and divided them into patients with (cases) and without cirrhosis (controls). All patients were followed up from the index month (exact month of diagnosis) to the end of 2013, death, or study outcome, whichever occurred first. The cases and controls were 1:6 propensity score matched for age, sex, and exact month of diagnosis; finally, 8078 patients (1154 with and 6924 without cirrhosis) were included in the analysis. The presence of coexisting EHMs and a new diagnosis of cirrhosis was analyzed. Adjusted hazard ratios (HRs) and cumulative incidence for cirrhosis were calculated in conditional Cox regression models after propensity score matching. Patients with high-cirrhosis-risk EHMs, such as DM (HR: 1.72, 95% CI: 1.51-1.96, P < .001), HCD (HR: 1.45, 95% CI: 1.27-1.67, P < .007), CKD (HR: 1.21, 95% CI: 1.05-1.38, P < .001), hyperlipidemia (HR: 0.53, 95% CI: 0.46-0.60, P < .001), lichen planus (HR: 2.71, 95% CI: 1.56-4.72, P < .001), and palpable purpura (HR: 2.67, 95% CI: 2.13-3.35, P < .001) exhibited significantly higher risk of liver cirrhosis than those without. Cumulative incidence (P < .001) of liver cirrhosis by pairwise comparisons of multiple high-cirrhosis-risk EHMs, and that of lichen planus was the highest. Our study provided direct estimates of specific HCV-associated EHM time trends of cirrhosis risk, with an upward trend in incidence. Lichen planus was at the top of the list of single-EHM comparisons, and the maximum combination of certain EHMs was the greatest risk factor across a different array of multi-EHM comparisons for liver cirrhosis development.
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Affiliation(s)
- Chun-Hsiang Wang
- Department of Hepatogastroenterology, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan
- Department of Optometry, Chung Hwa Medical University, Tainan, Taiwan
| | - Shih-Fang Ou
- Department of Hepatogastroenterology, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan
| | - Yuan-Tsung Tseng
- Committee of Medical Research, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan
- * Correspondence: Yuan-Tsung Tseng, MS, Committee of Medical Research, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Taiwan (e-mail: )
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El-Kassas M, Awad A. Metabolic aspects of hepatitis C virus. World J Gastroenterol 2022; 28:2429-2436. [PMID: 35979265 PMCID: PMC9258278 DOI: 10.3748/wjg.v28.i22.2429] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 03/18/2022] [Accepted: 04/22/2022] [Indexed: 02/06/2023] Open
Abstract
Many metabolic factors are associated with chronic hepatitis C virus (HCV) infection and can influence the course of the illness and impact the progression of liver and non-liver-related diseases through complex interactions. Several of these factors impact the course of chronic HCV (CHC) and result in the conceptual translation of CHC from a localized to systemic disease. Besides the traditional liver manifestations associated with CHC infection, such as cirrhosis and hepatocellular carcinoma, various extrahepatic disorders are associated with HCV infection, including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases. The coexistence of metabolic disorders and CHC is known to influence the chronicity and virulence of HCV and accelerates the progression to liver fibrosis and hepatocellular carcinoma. Insulin resistance is one of the key factors that have a tremendous metabolic impact on CHC. Therefore, there is a great need to properly evaluate patients with CHC infection and correct the modifiable metabolic risk factors. Furthermore, patients with HCV who achieved a sustained virological response showed an overall improvement in glucose metabolism, but the exact evidence still requires further studies with long-term follow-up. This review delineates the most recent evidence on the main metabolic factors associated with CHC and the possible influence of chronic HCV infection on metabolic features.
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Affiliation(s)
- Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo 11795, Egypt
| | - Abeer Awad
- Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 11566, Egypt
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Ciardullo S, Mantovani A, Ciaccio A, Carbone M, Invernizzi P, Perseghin G. Hepatitis C virus infection and diabetes: A complex bidirectional relationship. Diabetes Res Clin Pract 2022; 187:109870. [PMID: 35398458 DOI: 10.1016/j.diabres.2022.109870] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 03/22/2022] [Accepted: 04/04/2022] [Indexed: 11/03/2022]
Abstract
Chronic hepatitis C (CHC) and diabetes represent two severe chronic conditions responsible for a considerable number of deaths worldwide. They have a complex, bidirectional relationship. On the one hand, several cohort studies have shown that chronic HCV infection increases both the risk of developing diabetes in non-diabetic subjects (by inducing insulin resistance and promoting β-cell dysfunction) as well as the risk of developing macro and microvascular complications in patients with known diabetes; on the other hand, diabetes is an independent risk factor for liver-related events among patients with CHC, including a higher incidence of hepatocellular carcinoma, liver-related death and transplantation. Importantly, sustained virological response, which can be obtained in the vast majority of patients with the use of direct antiviral agents, does not only lead to a lower rate of liver-related outcomes, but also to improvements of glycemic control and reduction in the rate of complications among patients with diabetes. The aim of this review is to summarize available clinical evidence on the association among CHC, diabetes and related clinical outcomes. We will also briefly discuss the biological mechanisms underpinning the association between CHC and diabetes, as well as the implications this relationship should have on everyday clinical practice.
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Affiliation(s)
- Stefano Ciardullo
- Department of Medicine and Rehabilitation, Monza Policlinico di Monza, Monza, Italy; Department of Medicine and Surgery, University of Milan Bicocca, Monza, Italy.
| | - Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, University of Verona
| | - Antonio Ciaccio
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Marco Carbone
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Gianluca Perseghin
- Department of Medicine and Rehabilitation, Monza Policlinico di Monza, Monza, Italy; Department of Medicine and Surgery, University of Milan Bicocca, Monza, Italy
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Pandey B, Barnes RFW, Sun HL, Jackson S, Kruse-Jarres R, Quon DV, von Drygalski A. Risk of diabetes in haemophilia patients compared to clinic and non-clinic control cohorts. Haemophilia 2022; 28:445-452. [PMID: 35238443 DOI: 10.1111/hae.14515] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 01/19/2022] [Accepted: 02/04/2022] [Indexed: 01/10/2023]
Abstract
INTRODUCTION Ageing patients with haemophilia (PWH) develop cardiovascular risk factors impacting care. Little is known about the prevalence of diabetes in PWH and its relation to other comorbidities. AIM To examine the risk of diabetes for adult PWH compared to men from the general United States population (National Health and Nutrition Examination Surveys [NHANES]) and outpatients attending a Veterans Affairs Medical Center (VAMC) clinic. METHODS Retrospective cross-sectional design. PWH from four haemophilia centres (n = 690) were matched with random samples from NHANES and VAMC. Diabetes (yes/no) was the outcome, while age, body mass index (BMI), race and Hepatitis C (HCV; by serology) and human immunodeficiency virus (HIV) positivity were covariates. We fitted semiparametric generalized additive models (GAMs) in order to compare diabetes risk between cohorts. RESULTS Younger PWH were at lower risk of diabetes than NHANES or VAMC subjects irrespective of BMI. However, the risk of diabetes rose in older PWH and was closely associated with HCV. For HCV-negative subjects, the risk of diabetes was considerably lower for PWH than NHANES and VAMC subjects. The difference persisted after controlling for BMI and age, indicating that the low risk of diabetes in PWH cannot be explained by lean body mass alone. CONCLUSION Since many ageing PWH are HCV positive and therefore at heightened risk for diabetes, it is important to incorporate diabetes screening into care algorithms in Haemophilia Treatment Centers, especially since PWH are not always followed in primary care clinics.
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Affiliation(s)
- Braj Pandey
- Department of Primary Care, Veterans Affairs Medical Center, San Diego, California, USA.,Department of Medicine, University of California San Diego, San Diego, California, USA
| | - Richard F W Barnes
- Department of Medicine, University of California San Diego, San Diego, California, USA
| | | | | | | | - Doris V Quon
- Washington Center for Bleeding Disorders at Bloodworks NorthWest, Seattle, Washington, USA
| | - Annette von Drygalski
- Department of Medicine, University of California San Diego, San Diego, California, USA
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Moran CA, Collins LF, Beydoun N, Mehta PK, Fatade Y, Isiadinso I, Lewis TT, Weber B, Goldstein J, Ofotokun I, Quyyumi A, Choi MY, Titanji K, Lahiri CD. Cardiovascular Implications of Immune Disorders in Women. Circ Res 2022; 130:593-610. [PMID: 35175848 PMCID: PMC8869407 DOI: 10.1161/circresaha.121.319877] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Immune responses differ between men and women, with women at higher risk of developing chronic autoimmune diseases and having more robust immune responses to many viruses, including HIV and hepatitis C virus. Although immune dysregulation plays a prominent role in chronic systemic inflammation, a key driver in the development of atherosclerotic cardiovascular disease (ASCVD), standard ASCVD risk prediction scores underestimate risk in populations with immune disorders, particularly women. This review focuses on the ASCVD implications of immune dysregulation due to disorders with varying global prevalence by sex: autoimmune disorders (female predominant), HIV (male-female equivalent), and hepatitis C virus (male predominant). Factors contributing to ASCVD in women with immune disorders, including traditional risk factors, dysregulated innate and adaptive immunity, sex hormones, and treatment modalities, are discussed. Finally, the need to develop new ASCVD risk stratification tools that incorporate variables specific to populations with chronic immune disorders, particularly in women, is emphasized.
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Affiliation(s)
- Caitlin A. Moran
- Emory University School of Medicine, Department of Medicine, Division of Infectious Diseases, Atlanta, GA, USA
| | - Lauren F. Collins
- Emory University School of Medicine, Department of Medicine, Division of Infectious Diseases, Atlanta, GA, USA
| | - Nour Beydoun
- Emory University School of Medicine, Department of Medicine, Center for Heart Disease Prevention, Division of Cardiology and Emory Women’s Heart Center, Atlanta, GA, USA
| | - Puja K. Mehta
- Emory University School of Medicine, Department of Medicine, Center for Heart Disease Prevention, Division of Cardiology and Emory Women’s Heart Center, Atlanta, GA, USA
| | - Yetunde Fatade
- Emory University School of Medicine, Department of Medicine, Atlanta, GA, USA
| | - Ijeoma Isiadinso
- Emory University School of Medicine, Department of Medicine, Center for Heart Disease Prevention, Division of Cardiology and Emory Women’s Heart Center, Atlanta, GA, USA
| | - Tené T Lewis
- Emory University, Rollins School of Public Health, Department of Epidemiology, Atlanta, GA, USA
| | - Brittany Weber
- Harvard Medical School, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
| | - Jill Goldstein
- Massachusetts General Hospital, Department of Psychiatry, and Harvard Medical School, Departments of Psychiatry and Medicine, Boston, MA, USA
| | - Igho Ofotokun
- Emory University School of Medicine, Department of Medicine, Division of Infectious Diseases, Atlanta, GA, USA
| | - Arshed Quyyumi
- Emory University School of Medicine, Department of Medicine, Center for Heart Disease Prevention, Division of Cardiology and Emory Women’s Heart Center, Atlanta, GA, USA
| | - May Y. Choi
- Cumming School of Medicine, University of Calgary, Calgary, AB Canada
| | - Kehmia Titanji
- Emory University, Department of Medicine, Division of Endocrinology, Metabolism, and Lipids, Atlanta, GA, USA
| | - Cecile D. Lahiri
- Emory University School of Medicine, Department of Medicine, Division of Infectious Diseases, Atlanta, GA, USA
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Mazzaro C, Quartuccio L, Adinolfi LE, Roccatello D, Pozzato G, Nevola R, Tonizzo M, Gitto S, Andreone P, Gattei V. A Review on Extrahepatic Manifestations of Chronic Hepatitis C Virus Infection and the Impact of Direct-Acting Antiviral Therapy. Viruses 2021; 13:2249. [PMID: 34835054 PMCID: PMC8619859 DOI: 10.3390/v13112249] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 11/02/2021] [Accepted: 11/05/2021] [Indexed: 02/06/2023] Open
Abstract
Extrahepatic manifestations are a feature of chronic hepatitis C virus (HCV) infection. In the course of chronic HCV infection, about 70% of patients have one or more extrahepatic manifestations. The latter are often the first and only clinical sign of infection. Experimental and clinical data support a causal association for many extrahepatic manifestations and HCV infection, which include mixed cryoglobulinemia, non-Hodgkin lymphomas (NHL), cardiovascular disease, insulin resistance, type 2 diabetes, neurological and psychiatric disease and other rheumatic diseases. All these extrahepatic conditions influence the morbidity, quality of life and mortality of HCV-infected patients. Currently, interferon-free therapeutic regimens with direct-acting antiviral agents (DAA) offer the possibility of treatment to almost the entire infected population, irrespective of stage of cirrhosis and associated serious comorbidities, always maintaining a high efficacy and tolerability. Several studies have shown a close association between HCV clearance by DAAs and an improvement or reduction in the risk of extrahepatic manifestations. Patients with HCV after a sustained virologic response (SVR) by DAA treatment have a lower risk than non-responders of developing cryoglobulinemic vasculitis and B-cell non-Hodgkin's lymphomas. Furthermore, the SVR by DAA also reduces the risk of acute coronary syndrome, cardiovascular disease, insulin resistance and type 2 diabetes, and it improves atherosclerosis. HCV clearance by DAA also improves the quality of life and survival of patients with chronic HCV infection with associated extrahepatic diseases. Thus, DAAs should be initiated as early as possible in HCV patients with extrahepatic manifestations.
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Affiliation(s)
- Cesare Mazzaro
- Clinical Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy;
| | - Luca Quartuccio
- Rheumatology Clinic Department of Medicine (DAME), ASUFC, University of Udine, 34100 Udine, Italy;
| | - Luigi Elio Adinolfi
- Unit Internal Medicine, Department of Advanced Medical and Surgery Sciences, Luigi Vanvitelli University of Campania, 80100 Naples, Italy; (L.E.A.); (R.N.)
| | - Dario Roccatello
- Unit of Nefrology and Dialysis, Department of Clinical and Biological Sciences, San Giovanni Bosco Hospital, University of Turin,10092 Turin, Italy;
| | - Gabriele Pozzato
- Department of Clinical and Surgical Sciences, Maggiore Hospital University of Trieste, 34121 Trieste, Italy;
| | - Riccardo Nevola
- Unit Internal Medicine, Department of Advanced Medical and Surgery Sciences, Luigi Vanvitelli University of Campania, 80100 Naples, Italy; (L.E.A.); (R.N.)
| | - Maurizio Tonizzo
- Department of Internal Medicine Pordenone General Hospital, 33170 Pordenone, Italy;
| | - Stefano Gitto
- Department of Experimental and Clinical Medicine, University of Florence, 50100 Florence, Italy;
| | - Pietro Andreone
- Unit of Internal Medicine and Metabolic Medicine, University Hospital Moidena and Reggio Emilia, 41100 Modena, Italy;
| | - Valter Gattei
- Clinical Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy;
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12
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Kim T, Kim J. Factors Associated with Hepatitis C Antibody Positivity in Korean Adults: A Cross-Sectional Study Based on 2013-2018 Korea National Health and Nutrition Examination Survey. Healthcare (Basel) 2021; 9:healthcare9101366. [PMID: 34683045 PMCID: PMC8544486 DOI: 10.3390/healthcare9101366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 10/06/2021] [Accepted: 10/12/2021] [Indexed: 12/09/2022] Open
Abstract
This study aimed to provide basic data on the prevention of hepatitis C infection by identifying factors related to it based on the data from the National Health and Nutrition Examination Survey (KNHANES). The sixth (2013-2015) and seventh (2016-2018) Korean National Health and Nutrition Examination Surveys conducted by the Korean Disease Control and Prevention Agency were analyzed. This is a population-based, nationally representative, multistage, cross-sectional survey of noninstitutionalized persons in Korea. Multivariate regression analysis was used to assess the significance of the variables. A total of 32,942 persons aged >20 years were selected for this study. Among them, 282 tested positive for hepatitis C antibodies, while 32,660 tested negative. Of the 282 persons who tested positive, 48.6% were men and 51.4% were women. The factors associated with hepatitis C infection were age, education level, self-rated health status, and liver cirrhosis. Therefore, there is a need to educate people and implement preventive programs based on age and education levels to reduce the incidence of hepatitis C infections. In addition, it is necessary to include hepatitis C screening as part of the National Health Examination to diagnose hepatitis C infections.
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Affiliation(s)
- Taehui Kim
- Department of Nursing, Joongbu University, 201 Daehak-ro, Geumsan-gun 32713, Chungcheongnam-do, Korea;
| | - Jiyoung Kim
- Department of Nursing, Chungcheong University, 38 Wolgok-gil, Cheongju-si 28171, Chungcheongbuk-do, Korea
- Correspondence: ; Tel.: +82-43-230-2808
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13
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Calvaruso V, Petta S, Cacciola I, Cabibbo G, Cartabellotta F, Distefano M, Scifo G, Di Rosolini MA, Russello M, Prestileo T, Madonia S, Malizia G, Montineri A, Digiacomo A, Licata A, Benanti F, Bertino G, Enea M, Battaglia S, Squadrito G, Raimondo G, Cammà C, Craxì A, Di Marco V, Rete Sicilia Selezione Terapia ‐ HCV (RESIST‐HCV). Liver and cardiovascular mortality after hepatitis C virus eradication by DAA: Data from RESIST-HCV cohort. J Viral Hepat 2021; 28:1190-1199. [PMID: 33896097 PMCID: PMC8359835 DOI: 10.1111/jvh.13523] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 03/11/2021] [Accepted: 04/13/2021] [Indexed: 01/06/2023]
Abstract
Real-world evidence on the course of Hepatitis C Virus (HCV) chronic liver disease after Sustained Virologic Response (SVR) obtained with direct-acting antiviral drugs (DAAs) are still limited, and the effects on mortality remain unclear. We evaluated the post-treatment survival of 4307 patients in the RESIST-HCV cohort (mean age 66.3 ± 11.6 years, 56.9% males, 24.7% chronic hepatitis, 66.9% Child-Pugh A cirrhosis and 8.4% Child-Pugh B cirrhosis) treated with DAAs between March 2015 and December 2016 and followed for a median of 73 weeks (range 16-152). Proportional cause-specific hazard regression for competing risks was used to evaluate the survival and to assess the predictors of liver and cardiovascular death. Overall, 94.7% of patients achieved SVR while 5.3% were HCV RNA-positive at last follow-up. Sixty-three patients (1.4%) died during the observation period. SVR was associated with a decreased risk of liver mortality (hazard ratio,HR0.09, beta -2.37, p < .001). Also, platelet count (HR 0.99, beta-0.01, p = .007) and albumin value (HR 0.26, beta -1.36 p = .001) were associated with liver mortality by competing risk analysis. SVR was associated with a reduced risk of cardiovascular mortality regardless of presence of cirrhosis (HR 0.07, beta-2.67, p < .001). Presence of diabetes (HR 3.45, beta 1.24, p = .014) and chronic kidney disease class ≥3 (HR 3.60, beta 1.28, p = 0.016) were two factors independently associated with higher risk of cardiovascular mortality. Patients with SVR to a DAA therapy have a better liver and cardiovascular survival, and the effects of HCV eradication are most evident in patients with compensated liver disease.
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Affiliation(s)
- Vincenza Calvaruso
- Gastroenterology and Hepatology UnitDepartment of Health Promotion Sciences Maternal and Infantile CareInternal Medicine and Medical SpecialitiesPROMISEUniversity of PalermoPalermoItaly
| | - Salvatore Petta
- Gastroenterology and Hepatology UnitDepartment of Health Promotion Sciences Maternal and Infantile CareInternal Medicine and Medical SpecialitiesPROMISEUniversity of PalermoPalermoItaly
| | - Irene Cacciola
- UOC Epatologia Clinica e BiomolecolareMessinaItaly
- AOUP G. MartinoDipartimento di Medicina Interna e SperimentaleUniversity of MessinaMessinaItaly
| | - Giuseppe Cabibbo
- Gastroenterology and Hepatology UnitDepartment of Health Promotion Sciences Maternal and Infantile CareInternal Medicine and Medical SpecialitiesPROMISEUniversity of PalermoPalermoItaly
| | | | - Marco Distefano
- UOC Malattie InfettiveOspedale Umberto I di SiracusaASP SiracusaSiracusaItaly
| | - Gaetano Scifo
- UOC Malattie InfettiveOspedale Umberto I di SiracusaASP SiracusaSiracusaItaly
| | | | | | - Tullio Prestileo
- UOC Malattie InfettiveARNAS Civico‐Di Cristina‐BenefratelliPalermoItaly
| | | | | | - Arturo Montineri
- UOC Malattie infettiveAO Universitaria V. Emanuele di CataniaCataniaItaly
| | | | - Anna Licata
- UOC Medicina InternaAOUP Paolo GiacconePalermoItaly
| | | | - Gaetano Bertino
- UOC Medicina InternaAO Universitaria V. Emanuele di CataniaCataniaItaly
| | - Marco Enea
- Gastroenterology and Hepatology UnitDepartment of Health Promotion Sciences Maternal and Infantile CareInternal Medicine and Medical SpecialitiesPROMISEUniversity of PalermoPalermoItaly
| | - Salvatore Battaglia
- Gastroenterology and Hepatology UnitDepartment of Health Promotion Sciences Maternal and Infantile CareInternal Medicine and Medical SpecialitiesPROMISEUniversity of PalermoPalermoItaly
| | - Giovanni Squadrito
- UOC Epatologia Clinica e BiomolecolareMessinaItaly
- AOUP G. MartinoDipartimento di Medicina Interna e SperimentaleUniversity of MessinaMessinaItaly
| | - Giovanni Raimondo
- UOC Epatologia Clinica e BiomolecolareMessinaItaly
- AOUP G. MartinoDipartimento di Medicina Interna e SperimentaleUniversity of MessinaMessinaItaly
| | - Calogero Cammà
- Gastroenterology and Hepatology UnitDepartment of Health Promotion Sciences Maternal and Infantile CareInternal Medicine and Medical SpecialitiesPROMISEUniversity of PalermoPalermoItaly
| | - Antonio Craxì
- Gastroenterology and Hepatology UnitDepartment of Health Promotion Sciences Maternal and Infantile CareInternal Medicine and Medical SpecialitiesPROMISEUniversity of PalermoPalermoItaly
| | - Vito Di Marco
- Gastroenterology and Hepatology UnitDepartment of Health Promotion Sciences Maternal and Infantile CareInternal Medicine and Medical SpecialitiesPROMISEUniversity of PalermoPalermoItaly
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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: 4] [Impact Index Per Article: 1.0] [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.
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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
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15
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Jeong D, Karim ME, Wong S, Wilton J, Butt ZA, Binka M, Adu PA, Bartlett S, Pearce M, Clementi E, Yu A, Alvarez M, Samji H, Velásquez García HA, Abdia Y, Krajden M, Janjua NZ. Impact of HCV infection and ethnicity on incident type 2 diabetes: findings from a large population-based cohort in British Columbia. BMJ Open Diabetes Res Care 2021; 9:9/1/e002145. [PMID: 34099439 PMCID: PMC8186745 DOI: 10.1136/bmjdrc-2021-002145] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Accepted: 05/09/2021] [Indexed: 12/15/2022] Open
Abstract
INTRODUCTION Increasing evidence indicates that chronic hepatitis C virus (HCV) infection is associated with higher risk of diabetes. Previous studies showed ethnic disparities in the disease burden of diabetes, with increased risk in Asian population. We described the incidence of type 2 diabetes related to HCV infection and assessed the concurrent impact of HCV infection and ethnicity on the risk of diabetes. RESEARCH DESIGN AND METHODS In British Columbia Hepatitis Testers Cohort, individuals were followed from HCV diagnosis to the earliest of (1) incident type 2 diabetes, (2) death or (3) end of the study (December 31, 2015). Study population included 847 021 people. Diabetes incidence rates in people with and without HCV were computed. Propensity scores (PS) analysis was used to assess the impact of HCV infection on newly acquired diabetes. PS-matched dataset included 117 184 people. We used Fine and Gray multivariable subdistributional hazards models to assess the effect of HCV and ethnicity on diabetes while adjusting for confounders and competing risks. RESULTS Diabetes incidence rates were higher among people with HCV infection than those without. The highest diabetes incidence rate was in South Asians with HCV (14.7/1000 person-years, 95% CI 12.87 to 16.78). Compared with Others, South Asians with and without HCV and East Asians with HCV had a greater risk of diabetes. In the multivariable stratified analysis, HCV infection was associated with increased diabetes risk in all subgroups: East Asians, adjusted HR (aHR) 3.07 (95% CI 2.43 to 3.88); South Asians, aHR 2.62 (95% CI 2.10 to 3.26); and Others, aHR 2.28 (95% CI 2.15 to 2.42). CONCLUSIONS In a large population-based linked administrative health data, HCV infection was associated with higher diabetes risk, with a greater relative impact in East Asians. South Asians had the highest risk of diabetes. These findings highlight the need for care and screening for HCV-related chronic diseases such as type 2 diabetes among people affected by HCV.
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Affiliation(s)
- Dahn Jeong
- School of Population and Public Health, The University of British Columbia, Vancouver, British Columbia, Canada
- Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Mohammad Ehsanul Karim
- School of Population and Public Health, The University of British Columbia, Vancouver, British Columbia, Canada
- Centre for Health Evaluation and Outcome Sciences, St Paul's Hospital, Vancouver, British Columbia, Canada
| | - Stanley Wong
- Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - James Wilton
- Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Zahid Ahmad Butt
- Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
- School of Public Health and Health Systems, University of Waterloo, Waterloo, Ontario, Canada
| | - Mawuena Binka
- Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Prince Asumadu Adu
- School of Population and Public Health, The University of British Columbia, Vancouver, British Columbia, Canada
- Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Sofia Bartlett
- Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
- Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada
| | - Margo Pearce
- School of Population and Public Health, The University of British Columbia, Vancouver, British Columbia, Canada
- Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Emilia Clementi
- School of Population and Public Health, The University of British Columbia, Vancouver, British Columbia, Canada
- Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Amanda Yu
- Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Maria Alvarez
- Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Hasina Samji
- Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
- Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada
| | | | - Younathan Abdia
- School of Population and Public Health, The University of British Columbia, Vancouver, British Columbia, Canada
- Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Mel Krajden
- Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
- Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada
| | - Naveed Zafar Janjua
- School of Population and Public Health, The University of British Columbia, Vancouver, British Columbia, Canada
- Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
- Centre for Health Evaluation and Outcome Sciences, St Paul's Hospital, Vancouver, British Columbia, Canada
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16
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Estefan S, Brandão-Melo CE, Dos Santos Silva CM, Gomes DCK, Cardoso P, Costa MHS. Metabolic Evaluation in Patients With Hepatitis C Treated With Direct Antiviral Agents. Front Med (Lausanne) 2021; 8:631600. [PMID: 34136497 PMCID: PMC8200477 DOI: 10.3389/fmed.2021.631600] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 03/01/2021] [Indexed: 12/17/2022] Open
Abstract
Epidemiological data clearly indicate a link between hepatitis C virus (HCV) and altered glucose homeostasis. Objective: To evaluate the response of treatment with direct antiviral agents (DAAs) on metabolic variables of patients with hepatitis C. Methods: Observational, cross-sectional study in a sample of patients with hepatitis C starting therapy with DAAs followed on the hepatology division of Federal University of Rio de Janeiro State. Data were collected in two stages: before the start of therapy and between 12 and 52 weeks after obtaining the sustained virological response. Results: In the baseline assessment of the 97 patients selected, 19.3% were obese, 38.6% were overweight, 50% were hypertensive, 43.8% were pre-diabetic, 12.5% were diabetic, 31.2% were dyslipidemic, and 21.8% had metabolic syndrome. There was an increase in total cholesterol and LDL levels (p < 0.001), and a non-significant reduction in blood glucose, glycated hemoglobin, insulin, and HOMA-IR levels after treatment. In the post-treatment, there was a reduction in fibrosis (p = 0.016), with a reduction in the levels of GGT, AST, and ALT (all with p < 0.001), as well as in the FIB4 and APRI scores (both with p < 0.001) and in the degree of fibrosis evaluated by elastography represented in kPa (p = 0.006). The blood glucose level was higher in patients with steatosis (p = 0.039) after treatment. There was a positive pre-treatment correlation between the degree of fibrosis (kPa) and FIB4 (r = 0.319, p = 0.004), APRI (r = 0.287, p = 0.010), and the NAFLD score (r = 0.275, p = 0.016). Conclusion: Patients with hepatitis C had a high prevalence of metabolic disturbance in the pre-treatment phase, but the therapy did not show beneficial effects, especially on glucose metabolism.
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Affiliation(s)
- Sergio Estefan
- Endocrinology and Hepatology Division of Federal University of Rio de Janeiro State, Rio de Janeiro, Brazil
| | | | | | - Danilo Cosme Klein Gomes
- Endocrinology and Hepatology Division of Federal University of Rio de Janeiro State, Rio de Janeiro, Brazil
| | - Paula Cardoso
- Endocrinology and Hepatology Division of Federal University of Rio de Janeiro State, Rio de Janeiro, Brazil
| | - Marcia Helena S Costa
- Endocrinology and Hepatology Division of Federal University of Rio de Janeiro State, Rio de Janeiro, Brazil
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17
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Wu A, Burrowes S, Zisman E, Brown TT, Bagchi S. Association of hepatitis C infection and acute coronary syndrome: A case-control study. Medicine (Baltimore) 2021; 100:e26033. [PMID: 34032724 PMCID: PMC8154507 DOI: 10.1097/md.0000000000026033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 04/30/2021] [Accepted: 05/03/2021] [Indexed: 01/04/2023] Open
Abstract
ABSTRACT Infections with hepatitis C virus (HCV) represent a substantial national and international public health burden. HCV has been associated with numerous extrahepatic conditions and can lead to metabolic derangements that are associated with atherosclerosis and cardiovascular disease. We investigated whether HCV infection is associated with an increased number of acute coronary syndrome (ACS) events among hospitalized patients in an inner-city tertiary hospital.We performed a matched (age, sex, and race/ethnicity) case-control study on patients at least 18 years old admitted to inpatient medical and cardiac services at the University of Maryland Medical Center from 2015 through 2018. The primary outcome was ACS and the primary exposure was HCV infection. Covariates of interest included: alcohol use, tobacco use, illicit drug use, hypertension, diabetes mellitus, human immunodeficiency virus infection, body mass index, dyslipidemia, and family history of coronary heart disease. Covariates with significant associations with both exposure and outcome in bivariate analyses were included in the multivariable analyses of the final adjusted model.There were 1555 cases and 3110 controls included in the final sample. Almost 2% of cases and 2.4% of controls were HCV infected. In adjusted models, there was no significant association found between experiencing an ACS event in those with HCV infection compared to those without HCV infection (odds ratio 0.71, 95% confidence interval 0.45-1.11).We found no significant association between HCV infection and ACS in our study population. However, given the mixed existing literature, the association between HCV and ACS warrants further investigation in future prospective cohort and/or interventional studies.
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Affiliation(s)
- Angela Wu
- University of Maryland School of Medicine, Baltimore, MD
| | - Shana Burrowes
- Section of Infectious Diseases, Boston University School of Medicine, Boston, MA
| | - Erin Zisman
- University of Maryland School of Medicine, Baltimore, MD
| | - Todd Tarquin Brown
- Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University
| | - Shashwatee Bagchi
- Section of Infectious Diseases, University of Maryland School of Medicine
- Institute of Human Virology, University of Maryland School of Medicine
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18
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Roguljic H, Nincevic V, Bojanic K, Kuna L, Smolic R, Vcev A, Primorac D, Vceva A, Wu GY, Smolic M. Impact of DAA Treatment on Cardiovascular Disease Risk in Chronic HCV Infection: An Update. Front Pharmacol 2021; 12:678546. [PMID: 34045969 PMCID: PMC8144519 DOI: 10.3389/fphar.2021.678546] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 04/27/2021] [Indexed: 12/31/2022] Open
Abstract
Hepatitis C virus (HCV) infection is a systemic disease associated with multiple significant extrahepatic manifestations. Emerging studies indicate association between the HCV infection and a higher incidence of major adverse cardiovascular events such as: coronary artery disease, heart failure, stroke and peripheral artery disease, when compared to general population. Atherosclerosis is a common pathophysiologic mechanism of cardiovascular disease (CVD) development which is the leading cause of mortality in the Western world. Proposed mechanisms of HCV-induced atherosclerosis includes systemic inflammation due to the chronic infection with increased levels of pro-atherogenic cytokines and chemokines. Furthermore, it has been demonstrated that HCV exists and replicates within atheroschlerotic plaques, supporting the theory of direct pro-atherogenic effect of the virus. Direct acting antiviral agents (DAAs) represent a safe and highly effective treatment of HCV infection. Beside the improvement in liver-related outcomes, DAAs exhibit a beneficial effect on extra-hepatic manifestations of chronic HCV infection. Recently, it has been shown that patients with chronic HCV infection treated with DAA-based therapeutic regimes had a 43% reduction of CVD events incidence risk. Moreover, eradication of HCV with DAAs results in a significant positive effect on risk factors for cardiovascular disease, despite a general worsening of the lipid profile. This positive effects is mainly due to an improvement of endothelial function and glucose metabolism. Although DAA treatment is associated with a beneficial impact on cardiovascular events, further studies are needed to fully elucidate the mechanisms responsible.
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Affiliation(s)
- Hrvoje Roguljic
- Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, Osijek, Croatia
- University Hospital Osijek, Osijek, Croatia
- Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, Osijek, Croatia
| | - Vjera Nincevic
- Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, Osijek, Croatia
- Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, Osijek, Croatia
| | - Kristina Bojanic
- Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, Osijek, Croatia
- Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, Osijek, Croatia
- Health Center Osijek, Osijek, Croatia
| | - Lucija Kuna
- Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, Osijek, Croatia
- Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, Osijek, Croatia
| | - Robert Smolic
- Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, Osijek, Croatia
- Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, Osijek, Croatia
| | - Aleksandar Vcev
- Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, Osijek, Croatia
- University Hospital Osijek, Osijek, Croatia
- Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, Osijek, Croatia
| | - Dragan Primorac
- Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, Osijek, Croatia
- Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, Osijek, Croatia
- St. Catherine Specialty Hospital, Zabok, Croatia
- Eberly College of Science, The Pennsylvania State University, State College, PA, United States
- The Henry C. Lee College of Criminal Justice and Forensic Sciences, University of New Haven, West Haven, CT, United States
- Medical School, University of Split, Split, Croatia
- Medical School, University of Rijeka, Rijeka, Croatia
- Medical School REGIOMED, Coburg, Germany
- Medical School, University of Mostar, Mostar, Bosnia and Herzegovina
| | - Andrijana Vceva
- Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, Osijek, Croatia
- University Hospital Osijek, Osijek, Croatia
| | - George Y. Wu
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, United States
| | - Martina Smolic
- Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, Osijek, Croatia
- Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, Osijek, Croatia
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19
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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.
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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
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Impact of DAA-Based Regimens on HCV-Related Extra-Hepatic Damage: A Narrative Review. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1323:115-147. [PMID: 33326112 DOI: 10.1007/5584_2020_604] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Two-third of patients with chronic hepatitis C show extrahepatic manifestations due to HCV infection of B lymphocytes, such as mixed cryoglobulinemia and non-Hodgkin B-cell lymphoma, or develop a chronic inflammatory status that may favor the development of adverse cardiovascular events, kidney diseases or metabolic abnormalities.DAAs treatments induce HCV eradication in 95% of treated patients, which also improves the clinical course of extrahepatic manifestations, but with some limitations. After HCV eradication a good compensation of T2DM has been observed, but doubts persist about the possibility of obtaining a stable reduction in fasting glucose and HbA1c levels.Chronic HCV infection is associated with low total and LDL cholesterol serum levels, which however increase significantly after HCV elimination, possibly due to the disruption of HCV/lipid metabolism interaction. Despite this adverse effect, HCV eradication exerts a favorable action on cardiovascular system, possibly by eliminating numerous other harmful effects exerted by HCV on this system.DAA treatment is also indicated for the treatment of patients with mixed cryoglobulinemia syndrome, since HCV eradication results in symptom reduction and, in particular, is effective in cryoglobulinemic vasculitis. Furthermore, HCV eradication exerts a favorable action on HCV-related lymphoproliferative disorders, with frequent remission or reduction of clinical manifestations.There is also evidence that HCV clearance may improve impaired renal functions, but same conflicting data persist on the effect of some DAAs on eGFR.
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21
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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.
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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
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22
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Impact of HCV cure with drug-acting antivirals in the use of concomitant medication and lipid profile: follow-up data 2 years after the sustained virological response. Eur J Gastroenterol Hepatol 2021; 32:214-222. [PMID: 32195695 DOI: 10.1097/meg.0000000000001714] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND AND AIM Patients with chronic hepatitis C (CHC) frequently associated comorbidities and concomitant medication. Sustained virological response (SVR12) has been related to an increase in cholesterol serum levels and in peripheral vascular resistance. Our aim was to evaluate the impact of SVR12 on the use of concomitant medication and serum lipid profile. METHODS Prospective study including patients treated with direct-acting antivirals who had achieved the SVR12. Clinical data and concomitant drugs were analysed at baseline and at least 1 year after SVR12. Differences from baseline to follow-up in the concomitant medication were evaluated by Stuart-Maxwell test and lipid profile by Wilcoxon signed-rank test. Patients were categorized according to the increase/decrease in the number of drugs included in each class (Anatomical Therapeutic Chemical classification system). RESULTS Two hundred twenty-six patients with SVR12 were included, 73.5% were receiving concomitant drugs (49.6% with antihypertensive effect, 30.5% antacids, 16.4% anti-diabetic drugs, and 7.1% lipid-lowering agents). One year after SVR12, total cholesterol serum levels increased from 161 to 179 mg/dl (P < 0.001) and, after a median time of 25.7 months, the use of lipid-lowering drugs increased from 7.8 to 11.5% (P = 0.009). In addition, we observed a trend to use more antihypertensive drugs in older patients (P = 0.06), especially in those with cirrhosis. Anxiolytics decreased after SVR12 from 13.7 to 10.6% (P = 0.035). CONCLUSION CHC cure is associated with a significant increase in cholesterol serum levels and the use of lipid-lowering agents, as well as the use of drugs with antihypertensive effect in older patients.
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Nevola R, Acierno C, Pafundi PC, Adinolfi LE. Chronic hepatitis C infection induces cardiovascular disease and type 2 diabetes: mechanisms and management. Minerva Med 2020; 112:188-200. [PMID: 33205641 DOI: 10.23736/s0026-4806.20.07129-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Despite the availability of effective treatments, hepatitis C virus (HCV) still remains a threat to public health. HCV is capable to trigger, behind liver damage, extrahepatic manifestations, including cardiovascular disease and type 2 diabetes (T2DM). A close association has been reported between HCV infection and cardiovascular disease due to imbalances in metabolic pathways and chronic inflammation. HCV through both direct and indirect mechanisms causes a higher incidence of ischemic stroke, acute coronary syndrome, heart failure and peripheral arterial disease. In addition, a higher risk of death from cardiovascular events has been showed in HCV patients. Insulin resistance is a hallmark of HCV infection and represents the link between HCV and T2DM, which is one of the most frequent HCV-associated extrahepatic manifestations. The pathological basis of the increased risk of T2DM in HCV infection is provided by the alterations of the molecular mechanisms of IR induced both by the direct effects of the HCV proteins, and by the indirect effects mediated by chronic inflammation, oxidative stress and hepatic steatosis. T2DM increases the risk of compensated and decompensate cirrhosis and hepatocellular carcinoma as well as increases the risk of cardiovascular disease, lower limb amputation and end stage renal disease. Current evidence suggests that HCV eradication reduces the incidence and mortality of cardiovascular disease and T2DM, further underling the importance of public health strategies for eradication the infection. The aim of this review was to update evidence and management of interaction between HCV, cardiovascular disease, and T2DM in the era of DAA treatment.
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Affiliation(s)
- Riccardo Nevola
- Unit of Internal Medicine, Department of Advanced Medical and Surgery Sciences, Luigi Vanvitelli University of Campania, Naples, Italy
| | - Carlo Acierno
- Unit of Internal Medicine, Department of Advanced Medical and Surgery Sciences, Luigi Vanvitelli University of Campania, Naples, Italy
| | - Pia C Pafundi
- Unit of Internal Medicine, Department of Advanced Medical and Surgery Sciences, Luigi Vanvitelli University of Campania, Naples, Italy
| | - Luigi E Adinolfi
- Unit of Internal Medicine, Department of Advanced Medical and Surgery Sciences, Luigi Vanvitelli University of Campania, Naples, Italy -
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Mazzaro C, Mauro E, Ermacora A, Doretto P, Fumagalli S, Tonizzo M, Toffolutti F, Gattei V. Hepatitis C virus-related cryoglobulinemic vasculitis. Minerva Med 2020; 112:175-187. [PMID: 33198444 DOI: 10.23736/s0026-4806.20.07120-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Hepatitis C virus (HCV) infection affects about 170 million people worldwide. HCV is responsible for both hepatitis and extra-hepatic manifestations. Chronic infection has been shown to develop in about 70% of cases, and it can progress to cirrhosis or hepatocellular carcinoma. Ten percent of HCV patients may develop extra-hepatic manifestations, including mixed cryoglobulinemia (MC) and non-Hodgkin lymphomas (NHL). Cryoglobulinemic vasculitis (CV) varies, ranging from mild-moderate clinical symptoms (purpura on the legs, asthenia and arthralgias) and chronic hepatitis to severe symptoms (ulcers on the legs, peripheral neuropathy, glomerulonephritis, low-grade NHL to life threatening complications (rapid progressive glomerulonephritis, gastrointestinal vasculitis, acute hyper-viscosity). EVIDENCE ACQUISITION CV is associated with significant morbidity and mortality. Some studies have shown kidney involvement, cirrhosis, central nervous system involvement, and heart involvement as unfavorable prognostic factors. Many studies have demonstrated that, after antiviral therapy, CV can disappear along with HCV. After the introduction of the new direct antiviral agents (DAAs), the combination of pegylated interferon and ribavirin has been abandoned. EVIDENCE SYNTHESIS Several studies on new DAAs have reported remarkable 90% to 100% HCV eradication rates, regardless of genotype. Treatment with DAAs has comparable efficacy on viral eradication in CV patients but definite clinical improvements of vasculitis can be observed only in half the patients. CONCLUSIONS In patients with mild to moderate CV disease, DAAs therapy should be used as first line approach. In patients with severe vasculitis, DAAs therapy and a second-line treatment with RTX with or without aphaeresis are a required.
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Affiliation(s)
- Cesare Mazzaro
- Unit of Clinical of Experimental Onco-Hematology, IRCCS Centro di Riferimento Oncologico (CRO), Aviano, Pordenone, Italy -
| | - Endri Mauro
- Unit of Hematology, Department of Internal Medicine, Cà Foncello Hospital, Treviso, Italy
| | - Anna Ermacora
- Department of Internal Medicine, Pordenone General Hospital, Pordenone, Italy
| | - Paolo Doretto
- Unit of Laboratory, Pordenone General Hospital, Pordenone, Italy
| | - Silvia Fumagalli
- Unit of Hematology, Department of Internal Medicine, Cà Foncello Hospital, Treviso, Italy
| | - Maurizio Tonizzo
- Department of Internal Medicine, Pordenone General Hospital, Pordenone, Italy
| | - Federica Toffolutti
- Unit of Cancer Epidemiology, IRCCS Centro di Riferimento Oncologico (CRO), Aviano, Pordenone, Italy
| | - Valter Gattei
- Unit of Clinical of Experimental Onco-Hematology, IRCCS Centro di Riferimento Oncologico (CRO), Aviano, Pordenone, Italy
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Ndako JA, Owolabi AO, Olisa JA, Akinwumi JA, Dojumo VT, Olatinsu O, Adebayo BA. Studies on the prevalence of Hepatitis C virus infection in diabetic patients attending a tertiary health-care facility South-west Nigeria. BMC Infect Dis 2020; 20:664. [PMID: 32907538 PMCID: PMC7488326 DOI: 10.1186/s12879-020-05388-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Accepted: 08/31/2020] [Indexed: 02/08/2023] Open
Abstract
Background Hepatitis C virus (HCV) infection and type 2 diabetes mellitus (T2DM) are two major public health problems associated with increasing complications and mortality rates worldwide. The objective of this study is to evaluate the prevalence of hepatitis C virus (HCV) infection in diabetic patients and to investigate the influence of several epidemiological and clinical factors on HCV infection. Method A total number of one hundred and eighty diabetic patients were recruited for this study. Consented subjects made up of 71(39.4%) males and 109(60.56%) females were recruited for the study. While one-Hundred (100) Non-Diabetics (Controls) were also recruited for the study. Structured questionnaires were administered to the consented participants to obtain relevant data. Sera samples were assayed for antibodies to HCV using an enzyme linked immunosorbent assay [Inteco Diagnostic Limited]. ELISA technique. Result Overall prevalence of HCV infection among diabetes patients assayed was 13.3% out of which 8(11.3%) was obtained from the male subjects compared to 16 (14.7%) seropositivity recorded among the females (P = 0.511; P > 0.05). Considering age distribution, Subjects aged 41–50 years recorded, 9 (22.5%) positivity (P = 0.238; P > 0.05).Considering educational status of subjects screened, 22 (14.9%) positivity was rescored among subjects who have attained tertiary status of education.(P = 0.574;P > 0.05).Risk factors considered showed that, 7 (18.9%) seropositive subject were alcoholic consumers(P value = 0.2621;P > 0.05) while 5 (8.9%) recorded history of sharing sharp objects P = 0.2427;P > 0.05). Conclusion Our study shows a slightly higher prevalence of hepatitis C infection in type 2 diabetics. This call for urgent routine screening exercise among diabetic patients for HCV infection. This study also emphasizes the need for public enlightenment on the association between HCV infection and T2DM, to avert possible complications among diabetic patients.
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Affiliation(s)
- James A Ndako
- Department of Microbiology, Landmark University, Omu-aran, Nigeria.
| | | | - Joseph A Olisa
- Department of Medical Services, Landmark University Medical Center, LMU, Omu-aran, Nigeria
| | - Jeremiah A Akinwumi
- Department of Medical Laboratory Services, Landmark University Medical Center, LMU, Omu-aran, Nigeria
| | - Victor T Dojumo
- Department of Medical Laboratory Services, Landmark University Medical Center, LMU, Omu-aran, Nigeria
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de Castro GLC, Bichara CDA, Santiago AM, de Brito WB, Pereira LMS, Moura TCF, da Silva Graça Amoras E, de Araújo MSM, da Silva Conde SRS, Queiroz MAF, Ishak R, Vallinoto ACR. Polymorphisms in the TGFB1 and FOXP3 genes are associated with the presence of antinuclear antibodies in chronic hepatitis C. Heliyon 2020; 6:e04524. [PMID: 32743104 PMCID: PMC7387822 DOI: 10.1016/j.heliyon.2020.e04524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 05/11/2020] [Accepted: 07/17/2020] [Indexed: 11/18/2022] Open
Abstract
Chronic infection with Hepacivirus C (HCV) can lead to the occurrence of antinuclear antibodies (ANAs) and changes in cytokine profiles that can be similar to autoimmune diseases. The aim of the study was to identify polymorphisms in important mediators of the immune response in association with ANAs, which could contribute to the development of autoimmunity in hepatitis C. The study included 87 patients with chronic hepatitis C who were evaluated for the presence of ANA (indirect immunofluorescence) and for polymorphisms in the FOXP3, IFNG, IL6, IL8, IL10, MBL2, CRP, TGFΒ1 and TNFA genes (real-time PCR). Of the patients evaluated, 17 (19.54%) had ANA reactivity. The G allele of the FOXP3 rs2232365 polymorphism was more frequent in ANA-positive women (p = 0.0231; OR = 3,285). The C allele of the TGFΒ1 rs1800469 polymorphism was associated with ANA production (p = 0.0169; OR = 2.88). The results suggest that polymorphisms in genes related to immunological regulation may be associated with mechanisms that lead to the emergence of autoantibodies in the context of chronic Hepacivirus C infection.
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Affiliation(s)
| | - Carlos David A. Bichara
- Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil
| | - Angélica Menezes Santiago
- Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil
| | - William Botelho de Brito
- Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil
| | | | | | | | - Mauro Sérgio Moura de Araújo
- Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil
- Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, PA, Brazil
| | | | | | - Ricardo Ishak
- Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil
| | - Antonio Carlos Rosário Vallinoto
- Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil
- Corresponding author.
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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.
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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.
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Badawi A, Di Giuseppe G, Gupta A, Poirier A, Arora P. Bayesian network modelling study to identify factors influencing the risk of cardiovascular disease in Canadian adults with hepatitis C virus infection. BMJ Open 2020; 10:e035867. [PMID: 32371519 PMCID: PMC7228556 DOI: 10.1136/bmjopen-2019-035867] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
OBJECTIVES The present study evaluates the extent of association between hepatitis C virus (HCV) infection and cardiovascular disease (CVD) risk and identifies factors mediating this relationship using Bayesian network (BN) analysis. DESIGN AND SETTING A population-based cross-sectional survey in Canada. PARTICIPANTS Adults from the Canadian Health Measures Survey (n=10 115) aged 30 to 74 years. PRIMARY AND SECONDARY OUTCOME MEASURES The 10-year risk of CVD was determined using the Framingham Risk Score in HCV-positive and HCV-negative subjects. Using BN analysis, variables were modelled to calculate the probability of CVD risk in HCV infection. RESULTS When the BN is compiled, and no variable has been instantiated, 73%, 17% and 11% of the subjects had low, moderate and high 10-year CVD risk, respectively. The conditional probability of high CVD risk increased to 13.9%±1.6% (p<2.2×10-16) when the HCV variable is instantiated to 'Present' state and decreased to 8.6%±0.2% when HCV was instantiated to 'Absent' (p<2.2×10-16). HCV cases had 1.6-fold higher prevalence of high-CVD risk compared with non-infected individuals (p=0.038). Analysis of the effect modification of the HCV-CVD relationship (using median Kullback-Leibler divergence; DKL ) showed diabetes as a major effect modifier on the joint probability distribution of HCV infection and CVD risk (DKL =0.27, IQR: 0.26 to 0.27), followed by hypertension (0.24, IQR: 0.23 to 0.25), age (0.21, IQR: 0.10 to 0.38) and injection drug use (0.19, IQR: 0.06 to 0.59). CONCLUSIONS Exploring the relationship between HCV infection and CVD risk using BN modelling analysis revealed that the infection is associated with elevated CVD risk. A number of risk modifiers were identified to play a role in this relationship. Targeting these factors during the course of infection to reduce CVD risk should be studied further.
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Affiliation(s)
- Alaa Badawi
- Public Health Risk Sciences Division, Public Health Agency of Canada, Toronto, Ontario, Canada
- Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Giancarlo Di Giuseppe
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
- Pediatric Oncology Group of Ontario, Toronto, Ontario, Canada
| | - Alind Gupta
- Lighthouse Outcomes, Toronto, Ontario, Canada
| | - Abbey Poirier
- Department of Cancer Epidemiology and Prevention Research, Alberta Health Services, Calgary, Alberta, Canada
| | - Paul Arora
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
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Collins LF, Adekunle RO, Cartwright EJ. Metabolic Syndrome in HIV/HCV Co-infected Patients. CURRENT TREATMENT OPTIONS IN INFECTIOUS DISEASES 2020; 11:351-371. [PMID: 32030090 DOI: 10.1007/s40506-019-00207-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Purpose of review We review the scope and burden of metabolic syndrome in HIV/HCV co-infected patients, risk factors and potential mechanisms driving the increased cardio-metabolic risk in this population, and discuss relevant clinical considerations for management in the era of highly effective antiretroviral therapy (ART) and curative anti-HCV direct-acting antivirals. Recent findings HIV/HCV co-infected patients are at elevated risk of metabolic syndrome, attributed to (1) patient-specific factors, (2) viral-mediated effects, and (3) ART exposure. Risk factors for cardio-metabolic disorders are common in this population and include poor socioeconomic conditions, substance use, cardiovascular comorbidities, and liver/kidney disease. Chronic HIV/HCV infection induces an inflammatory and immune activated state in the host leading to alterations in glucose and lipid metabolism. Selection of life-saving ART must carefully consider the differential metabolic risk associated with each drug class and agent, such as dyslipidemia, hyperglycemia and insulin resistance, weight gain and hypertension. Emerging evidence supports metabolic derangements in chronic HCV may be improved by viral eradication with direct-acting antivirals, however, additional study in HIV/HCV co-infected patients is needed. Summary Future research programs should aim to better characterize metabolic syndrome in HIV/HCV co-infected patients with the goal of improved screening, treatment and prevention.
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Affiliation(s)
- Lauren F Collins
- Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Ruth O Adekunle
- Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Emily J Cartwright
- Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.,Atlanta VA Medical Center, Decatur, GA, USA
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Poliwczak AR, Białkowska J, Woźny J, Koziróg M, Bała A, Jabłkowski M. Cardiovascular risk assessment by electrocardiographic Holter monitoring in patients with chronic hepatitis C. Arch Med Sci 2020; 16:1031-1039. [PMID: 32863991 PMCID: PMC7444696 DOI: 10.5114/aoms.2020.96600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Accepted: 03/05/2018] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Cardiovascular diseases are ranked as the third cause of mortality among people infected with hepatitis C virus (HCV), but the relationship of infection with cardiovascular risk remains disputable. We have focused on the comprehensive use of parameters obtainable during long-term electrocardiographic (ECG) Holter monitoring. MATERIAL AND METHODS Heart rate variability and turbulence (HRV and HRT), deceleration/acceleration capacity (DC/AC), corrected QT interval (QTc) and late potential (LP) were used. 36 persons were included, and 30 healthy subjects formed a control group. All were submitted to 24-hour Holter ECG-monitoring. RESULTS The studied groups were not statistically significantly different with regards to basic anthropometric parameters. Statistically significantly higher medium and maximum heart rhythm and aminotransferase activities were recorded in patients with hepatitis C. The HRV parameters r-MSSD, p50NN, HF, and absolute DC/AC values were significantly lower in the subjects with hepatitis C than those in the control group. The QTc interval, measured for nocturnal hours, was also significantly longer in that group. There were no differences in the albumin level or basic echocardiographic parameters, including left ventricle ejection fraction. Nor was there any difference in the HRT parameters, or LP. The most interesting observation was the positive correlation among the number of viral RNA copies and DC, and LF. CONCLUSIONS We confirmed the presence of autonomic disorders with prevalence of sympathetic system activity and prolonged QTc interval in patients with chronic hepatitis C. Those parameters significantly correlated with infection intensity. Our results suggest that HCV infection could be an independent cardiovascular risk factor, not associated with the lipid profile. Further prospective studies are needed.
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Affiliation(s)
- Adam R. Poliwczak
- Department of Human Physiology, Medical University of Lodz, Lodz, Poland
| | - Jolanta Białkowska
- Department of Infectious and Liver Diseases, Medical University of Lodz, Lodz, Poland
| | - Joanna Woźny
- Department of Infectious and Liver Diseases, Medical University of Lodz, Lodz, Poland
| | - Marzena Koziróg
- Department of Internal Diseases and Cardiac Rehabilitation, Medical University of Lodz, Lodz, Poland
| | - Agnieszka Bała
- Department of Internal Diseases and Clinical Pharmacology, Medical University of Lodz, Lodz, Poland
| | - Maciej Jabłkowski
- Department of Infectious and Liver Diseases, Medical University of Lodz, Lodz, Poland
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Marei ES, Gabr HM, Shaheen DS. Potential role of vaspin and apelin in chronic hepatitis C virus patients with and without diabetes. JOURNAL OF RADIATION RESEARCH AND APPLIED SCIENCES 2020. [DOI: 10.1080/16878507.2020.1715556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Rossi C, Jeong D, Wong S, McKee G, Butt ZA, Buxton J, Wong J, Darvishian M, Bartlett S, Samji H, Yu A, Binka M, Alvarez M, Adu PA, Tyndall M, Krajden M, Janjua NZ. Sustained virological response from interferon-based hepatitis C regimens is associated with reduced risk of extrahepatic manifestations. J Hepatol 2019; 71:1116-1125. [PMID: 31433302 DOI: 10.1016/j.jhep.2019.07.021] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Revised: 06/26/2019] [Accepted: 07/22/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS HCV infection is associated with several extrahepatic manifestations (EHMs). We evaluated the impact of sustained virological response (SVR) on the risk of 7 EHMs that contribute to the burden of extrahepatic disease: type 2 diabetes mellitus, chronic kidney disease or end-stage renal disease, stroke, ischemic heart disease, major adverse cardiac events, mood and anxiety disorders, and rheumatoid arthritis. METHODS A longitudinal cohort study was conducted using data from the British Columbia Hepatitis Testers Cohort, which included ~1.3 million individuals screened for HCV. We identified all HCV-infected individuals who were treated with interferon-based therapies between 1999 and 2014. SVR was defined as a negative HCV RNA test ≥24 weeks post-treatment or after end-of-treatment, if unavailable. We computed adjusted subdistribution hazard ratios (asHR) for the effect of SVR on each EHM using competing risk proportional hazard models. Subgroup analyses by birth cohort, sex, injection drug exposure and genotype were also performed. RESULTS Overall, 10,264 HCV-infected individuals were treated with interferon, of whom 6,023 (59%) achieved SVR. Compared to those that failed treatment, EHM risk was significantly reduced among patients with SVR for type 2 diabetes mellitus (asHR 0.65; 95%CI 0.55-0.77), chronic kidney disease or end-stage renal disease (asHR 0.53; 95% CI 0.43-0.65), ischemic or hemorrhagic stroke (asHR 0.73; 95%CI 0.49-1.09), and mood and anxiety disorders (asHR 0.82; 95%CI 0.71-0.95), but not for ischemic heart disease (asHR 1.23; 95%CI 1.03-1.47), major adverse cardiac events (asHR 0.93; 95%CI 0.79-1.11) or rheumatoid arthritis (asHR 1.09; 95% CI 0.73-1.64). CONCLUSIONS SVR was associated with a reduction in the risk of several EHMs. Increased uptake of antiviral therapy may reduce the growing burden of EHMs in this population. LAY SUMMARY We estimated the rates of chronic comorbidities other than liver disease between those who were cured and those who failed treatment for hepatitis C virus (HCV) infection. Our findings showed that the rates of these non-liver diseases were largely reduced for those who were cured with interferon-based treatments. Early HCV treatments could provide many benefits in the prevention of various HCV complications beyond liver disease.
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Affiliation(s)
- Carmine Rossi
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Dahn Jeong
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Stanley Wong
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Geoffrey McKee
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Zahid Ahmad Butt
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Jane Buxton
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Jason Wong
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Maryam Darvishian
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Sofia Bartlett
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Hasina Samji
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Amanda Yu
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Mawuena Binka
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Maria Alvarez
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Prince Asumadu Adu
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Mark Tyndall
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Mel Krajden
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Naveed Zafar Janjua
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.
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Rosso C, Caviglia GP, Ciruolo M, Ciancio A, Younes R, Olivero A, Giordanino C, Troshina G, Abate ML, Rizzetto M, Pellicano R, Saracco GM, Bugianesi E, Smedile A. Clinical outcomes in chronic hepatitis C long-term responders to pre-direct antiviral agents: a single-center retrospective study. Minerva Med 2019; 110:401-409. [PMID: 31081312 DOI: 10.23736/s0026-4806.19.06108-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Obesity, type 2 diabetes (T2D), dyslipidemia, arterial hypertension as well as hepatic steatosis (HS) are common conditions that can affect clinical outcomes of patients with chronic hepatitis C (CHC) who achieved sustained virologic response (SVR). The aim of this study was to assess the impact of metabolic cofactors on the occurrence of clinical events during follow-up (FU) in a group of CHC long-term responders (LTRs) to interferon- (IFN) based therapy. METHODS A total of 5172 medical records of CHC patients enrolled from 1990 to 2011 were examined; 1034 of 5172 (20%) patients were treated with IFN-based therapy and 382 of 1034 (37%) of them achieved SVR. A total of 188 (49%) LTRs underwent liver biopsy before antiviral treatment. Data on liver and cardiometabolic events such as cirrhosis and its complications, hepatocellular carcinoma, coronary artery disease, arterial hypertension, impaired fasting glucose (IFG)/type 2 diabetes (T2D) and dyslipidemia, were collected over time. RESULTS The mean age of the whole cohort was 46±12 years and 114/188 (61%) patients were males. HS was found in 82 of 188 (43.6%) patients and most of them were infected by HCV genotype 3a. The prevalence of obesity, IFG/T2D, dyslipidemia and arterial hypertension was 4.3%, 6.9%, 37.2%, and 5.9%, and was similarly distributed among patients with and without HS. Cirrhosis was histologically diagnosed in 18 of 188 (9.6%) patients. After a median follow-up of 11 years (range 3-21 years), the cumulative incidence of cardiovascular events, IFG/T2D and dyslipidemia was higher in CHC-LTRs who had HS at baseline compared to those without HS (1.2%, 2.3%, and 3.0% vs. 0.4%, 0.8%, and 2.5%, respectively). At multivariable Cox regression analysis, HS was significantly associated to the development of cardiovascular events and IFG/T2D (HR=5.2, 95% CI: 1.3-20.7, P=0.019, and HR=2.6, 95% CI: 1.1-6.2, P=0.027, respectively). CONCLUSIONS In CHC-LTRs, HS at baseline may predispose to the development of cardiovascular events and T2D during follow-up emphasizing the importance of an accurate counseling in order to prevent extra-hepatic complications.
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Affiliation(s)
- Chiara Rosso
- Division of Gastroenterology, Department of Medical Sciences, University of Turin, Turin, Italy -
| | - Gian Paolo Caviglia
- Division of Gastroenterology, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Michela Ciruolo
- Division of Gastroenterology, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Alessia Ciancio
- Division of Gastroenterology, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Ramy Younes
- Division of Gastroenterology, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Antonella Olivero
- Division of Gastroenterology, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Chiara Giordanino
- Department of Gastro-Hepatology, Città della Salute e della Scienza University Hospital, Turin, Italy
| | - Giulia Troshina
- Division of Gastroenterology, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Maria Lorena Abate
- Division of Gastroenterology, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Mario Rizzetto
- Division of Gastroenterology, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Rinaldo Pellicano
- Department of Gastro-Hepatology, Città della Salute e della Scienza University Hospital, Turin, Italy
| | - Giorgio M Saracco
- Division of Gastroenterology, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Elisabetta Bugianesi
- Division of Gastroenterology, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Antonina Smedile
- Division of Gastroenterology, Department of Medical Sciences, University of Turin, Turin, Italy
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Liraglutide Inhibits Hepatitis C Virus Replication Through an AMP Activated Protein Kinase Dependent Mechanism. Int J Mol Sci 2019; 20:ijms20184569. [PMID: 31540136 PMCID: PMC6769880 DOI: 10.3390/ijms20184569] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2019] [Revised: 08/29/2019] [Accepted: 09/09/2019] [Indexed: 12/13/2022] Open
Abstract
Insulin resistance and diabetes are both associated with chronic hepatitis C virus (HCV) infection, and the glucagon-like peptide-1(GLP-1) receptor agonist, liraglutide, is a common therapy for diabetes. Our aim was to investigate whether liraglutide treatment can inhibit HCV replication. A cell culture-produced HCV infectious system was generated by transfection of in vitro-transcribed genomic JFH-1 ribonucleic acid (RNA) into Huh-7.5 cells. Total RNA samples were extracted to determine the efficiency of HCV replication. The Ava5 cells were treated with liraglutide and cell viability was calculated. A Western blot analysis of the protein expression was performed. The immunoreactive blot signals were also detected. Liraglutide activated GLP-1 receptors in the HCV infectious system, and inhibited subgenomic HCV RNA replication in the HuH-7.5 cells. The Western blot analysis revealed both HCV protein and replicon RNA were reduced after treatment with liraglutide in a dose-dependent manner. Liraglutide decreased the cell viability of HCV RNA at an optimum concentration of 120 μg/mL, activated the 5′ adenosine monophosphate-activated protein kinase (AMPK) and the phosphorylated- transducer of regulated cyclic adenosine monophosphate (CAMP) response element-binding protein 2 (TORC2), thereby decreasing the cell viability of phosphoenolpyruvate carboxykinase (PEPCK) and G6pase RNA Therefore, we conclude that liraglutide can inhibit HCV replication via an AMPK/TORC2-dependent pathway.
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Lin WY, Lin MS, Weng YH, Yeh TH, Lin YS, Fong PY, Wu YR, Lu CS, Chen RS, Huang YZ. Association of Antiviral Therapy With Risk of Parkinson Disease in Patients With Chronic Hepatitis C Virus Infection. JAMA Neurol 2019; 76:1019-1027. [PMID: 31168563 DOI: 10.1001/jamaneurol.2019.1368] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Importance Epidemiologic evidence suggests that hepatitis C virus (HCV) could be a risk factor for Parkinson disease (PD), but treatment for HCV infection has never been considered in these studies; hence, the association between antiviral therapy and PD incidence has remained unclear. Understanding this association may help in developing strategies to reduce PD occurrence. Objective To identify the risk of PD development in patients with HCV infection receiving antiviral treatment and in patients not receiving this treatment. Design, Setting, and Participants This cohort study obtained claims data from the Taiwan National Health Insurance Research Database. Adult patients with a new HCV diagnosis with or without hepatitis per International Classification of Diseases, Ninth Revision, Clinical Modification codes and anti-PD medications from January 1, 2003, to December 31, 2013, were selected for inclusion. After excluding participants not eligible for analysis, the remaining patients (n = 188 152) were categorized into treated and untreated groups according to whether they received antiviral therapy. Propensity score matching was performed to balance the covariates across groups for comparison of main outcomes. This study was conducted from July 1, 2017, to December 31, 2017. Main Outcomes and Measures Development of PD was the main outcome. A Cox proportional hazards regression model was used to compare the risk of PD, and the hazard ratio (HR) was calculated at 1 year, 3 years, and 5 years after the index date and at the end of the cohort. Results A total of 188 152 patients were included in the analysis. An equal number (n = 39 936) and comparable characteristics of participants were retained in the treated group (with 17 970 female [45.0%] and a mean [SD] age of 52.8 [11.4] years) and untreated group (with 17 725 female [44.4%] and a mean [SD] age of 52.5 [12.9] years) after matching. The incidence density of PD was 1.00 (95% CI, 0.85-1.15) in the treated group and 1.39 (95% CI, 1.21-1.57) per 1000 person-years in the untreated group. The advantage of antiviral therapy reached statistical significance at the 5-year follow-up (HR, 0.75; 95% CI, 0.59-0.96), and this advantage continued to increase until the end of follow-up (HR, 0.71; 95% CI, 0.58-0.87). Conclusions and Relevance Evidence suggested that the PD incidence was lower in patients with chronic HCV infection who received interferon-based antiviral therapy; this finding may support the hypothesis that HCV could be a risk factor for PD.
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Affiliation(s)
- Wey-Yil Lin
- Department of Neurology, Landseed International Hospital, Taoyuan, Taiwan.,Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.,Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
| | - Ming-Shyan Lin
- Department of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Yi-Hsin Weng
- Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.,Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.,School of Medicine, Chang Gung University, Taoyuan, Taiwan.,Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan
| | - Tu-Hsueh Yeh
- Department of Neurology, Taipei Medical University Hospital, Taipei, Taiwan.,School of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yu-Sheng Lin
- Department of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Po-Yu Fong
- Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.,Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.,School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yih-Ru Wu
- Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.,School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chin-Song Lu
- Department of Neurology, Landseed International Hospital, Taoyuan, Taiwan.,Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.,Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.,School of Medicine, Chang Gung University, Taoyuan, Taiwan.,Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan
| | - Rou-Shayn Chen
- Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.,Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.,School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ying-Zu Huang
- Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.,Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.,School of Medicine, Chang Gung University, Taoyuan, Taiwan.,Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan.,Institute of Cognitive Neuroscience, National Central University, Taoyuan, Taiwan
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Pavicic Ivelja M, Ivic I, Dolic K, Mestrovic A, Perkovic N, Jankovic S. Evaluation of cerebrovascular reactivity in chronic hepatitis C patients using transcranial color Doppler. PLoS One 2019; 14:e0218206. [PMID: 31185040 PMCID: PMC6559645 DOI: 10.1371/journal.pone.0218206] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Accepted: 05/27/2019] [Indexed: 12/18/2022] Open
Abstract
Hepatitis C viral (HCV) infection is associated with systemic inflammation and metabolic complications that might predispose patients to atherosclerosis, including cerebrovascular atherosclerosis. The aim of this study was to assess cerebrovascular reactivity in patients with chronic hepatitis C. Seventeen patients with chronic hepatitis C infection, as well as 11 healthy blood donors in the control group, were assessed for cerebrovascular reactivity according to the well-established breath-holding test that uses the transcranial color Doppler for measurement of blood flow velocity. Results obtained during the breath-holding revealed significantly lower average peak systolic (AvPS start, P = 0.018), end-diastolic (AvED start, P = 0.031) and mean velocity values at the very beginning of the breath-holding procedure (AvmeanV start, P = 0.02), as well as a lower mean peak systolic velocity at the end of the breath-holding test (AvPS max, P = 0.02) in the hepatitis C group. Vascular reactivity values, calculated as the breath-holding index, were also significantly lower (P = 0.045) in the hepatitis C group. In conclusion, the results of this study suggest an association between chronic HCV infection and altered cerebrovascular reactivity which may ultimately have an unfavorable effect on cerebrovascular hemodynamics and lead to increased risk of cerebrovascular diseases.
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Affiliation(s)
- Mirela Pavicic Ivelja
- Department of Infectious Diseases, University Hospital Split, Split, Croatia
- * E-mail:
| | - Ivo Ivic
- Department of Infectious Diseases, University Hospital Split, Split, Croatia
| | - Kresimir Dolic
- Department of Radiology, University Hospital Split, Split, Croatia
| | - Antonio Mestrovic
- Department of Gastroenterology and Hepatology, University Hospital Split, Split, Croatia
| | - Nikola Perkovic
- Department of Gastroenterology and Hepatology, University Hospital Split, Split, Croatia
| | - Stipan Jankovic
- Department of Radiology, University Hospital Split, Split, Croatia
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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: 10] [Impact Index Per Article: 1.7] [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.
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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.
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Lledó G, Benítez-Gutiérrez L, Arias A, Requena S, Cuervas-Mons V, de Mendoza C. Benefits of hepatitis C cure with antivirals: why test and treat? Future Microbiol 2019; 14:425-435. [PMID: 30900911 DOI: 10.2217/fmb-2019-0041] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection is one of the major causes of death worldwide due to infectious agents. The advent of direct-acting antivirals has dramatically improved the chance of HCV elimination, even for patients with decompensated cirrhosis. Along with HCV cure, benefits are recognized in terms of regression of liver fibrosis and risk of hepatocellular carcinoma. Furthermore, beyond hepatic outcomes, several extrahepatic benefits may result from sustained HCV eradication, including improvements in the neurocognitive function and reduced cardiovascular disease risk. Finally, there is no doubt that the individual success of direct-acting antivirals is largely contributing to halt HCV transmission globally, in the absence of an effective HCV prophylactic vaccine.
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Affiliation(s)
- Gema Lledó
- Internal Medicine Department, Hospital Puerta de Hierro-Majadahonda, Madrid, Spain
| | | | - Ana Arias
- Internal Medicine Department, Hospital Puerta de Hierro-Majadahonda, Madrid, Spain
| | - Silvia Requena
- Internal Medicine Department, Hospital Puerta de Hierro-Majadahonda, Madrid, Spain.,Internal Medicine Laboratory, Research Institute Puerta de Hierro-Segovia de Arana, Madrid, Spain
| | - Valentín Cuervas-Mons
- Internal Medicine Department, Hospital Puerta de Hierro-Majadahonda, Madrid, Spain.,Internal Medicine Laboratory, Research Institute Puerta de Hierro-Segovia de Arana, Madrid, Spain.,Universidad Autónoma, Madrid. Spain
| | - Carmen de Mendoza
- Internal Medicine Department, Hospital Puerta de Hierro-Majadahonda, Madrid, Spain.,Internal Medicine Laboratory, Research Institute Puerta de Hierro-Segovia de Arana, Madrid, Spain.,San Pablo-CEU University, Madrid. Spain
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Ye Y, Zhao X, Lu Y, Long B, Zhang S. Varinostat Alters Gene Expression Profiles in Aortic Tissues from ApoE -/- Mice. HUM GENE THER CL DEV 2018; 29:214-225. [PMID: 30284929 DOI: 10.1089/humc.2018.141] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Atherosclerosis (AS) is a complex, chronic inflammatory disease that is characterized by plaque buildup within arterial vessel walls. Preclinical trials have suggested that vorinostat, a pan-histone deacetylase inhibitor (HDACi), reduces vascular inflammation and AS, but the underlying protective mechanism has not been fully elucidated. The present study aimed to identify altered gene expression profiles in aortic tissues from ApoE-/- mice after vorinostat treatment. Male ApoE-/- mice fed a high-fat diet were treated with either vorinostat or vehicle, and the aortic plaque area was quantified 8 weeks after treatment. Aortic tissues were collected from both the vorinostat group (n = 3) and vehicle group (n = 3) for deep sequencing of the cDNA to construct sRNA libraries. Oral administration of vorinostat significantly reduced plaque size in the ApoE-/- mice (p < 0.05). In total, 1,550 differentially expressed mRNAs, 56 differentially expressed miRNAs, and 381 differentially expressed lncRNAs were identified in the vorinostat group compared to the vehicle group. Subsequently, a global lncRNA-miRNA-mRNA triple network was constructed based on the competitive endogenous RNA (ceRNA) theory. The hepatitis C signaling pathway was significantly enriched among the differentially expressed mRNAs from the ceRNA network, which suggests that vorinostat has anti-inflammatory properties. Importantly, the identified target pair of mmu-miR-3075-5p/lncRNA-A330023F24Rik/Ldlr may regulate drug response. Upregulation of low-density lipid receptor (Ldlr) and lncRNA-A330023F24Rik and downregulation of mmu-miR-3075-5p were further verified by quantitative real-time polymerase chain reaction. To conclude, vorinostat reduced AS in ApoE-/- mice. Differentially expressed mRNA, lncRNAs, and miRNAs, as well as their interactions and pathways, were identified, which partially explain vorinostat's anti-atherosclerotic effects.
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Affiliation(s)
- Yicong Ye
- 1 Department of Cardiology and Beijing Anzhen Hospital and Capital Medical University, Beijing, P.R. China.,2 Department of Department of Cardiology, Beijing Anzhen Hospital and Capital Medical University, Beijing, P.R. China
| | - Xiliang Zhao
- 1 Department of Cardiology and Beijing Anzhen Hospital and Capital Medical University, Beijing, P.R. China
| | - Yiyun Lu
- 1 Department of Cardiology and Beijing Anzhen Hospital and Capital Medical University, Beijing, P.R. China
| | - Bo Long
- 3 Department of Central Laboratory, Chinese Academy of Medical College and Peking Union Medical College Hospital, Peking Union Medical College Hospital, Beijing, P.R. China
| | - Shuyang Zhang
- 1 Department of Cardiology and Beijing Anzhen Hospital and Capital Medical University, Beijing, P.R. China
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Are direct-acting antivirals safe and effective in hepatitis C virus-cryoglobulinemia? virological, immunological, and clinical data from a real-life experience. Eur J Gastroenterol Hepatol 2018; 30:1208-1215. [PMID: 30138160 DOI: 10.1097/meg.0000000000001239] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Hepatitis C virus (HCV) is the major cause of cryoglobulinemia. Direct-acting antivirals (DAAs) have markedly changed the therapeutic outcomes in the treatment of patients with HCV. We evaluate the efficacy, safety, immunological, and clinical response of different DAA regimens in HCV-cryoglobulinemia. PATIENTS AND METHODS Ninety-three cryoglobulinemic patients, divided into symptomatic [symptomatic cryoglobulinemic patients (SCP; n=35)] and asymptomatic [nonsymptomatic cryoglobulinemic patients (NSCP; n=60)], underwent DAAs. Eighty-nine comparable noncryoglobulinemic patients were selected as a control group. We evaluated the sustained virological response (SVR), the adverse effects, and the immune and symptomatic response. RESULTS Percentages of patients who achieved SVR and experienced adverse effects were not statistically different between the three groups (100, 95, 93.3% and 57.1, 53.3, 48.3%). In 68.5% of SCP and in 76.7% of NSCP, cryoglobulins disappeared at SVR. No risk factor was associated with the persistence of cryoglobulins. An increase was observed both in C4 (P=0.002; P=0.018) and in C3 (P=0.0037; P=0.031) in SCP and NSCP. About 70% of symptomatic patients showed a complete or partial symptomatic remission: persistence of symptoms is correlated to the type of clinical picture. CONCLUSION DAA regimens are safe and effective in patients with HCV-cryoglobulinemia. The achievement of SVR is necessary, but not sufficient, to achieve a complete immunological and clinical response.
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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.
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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
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Lin MS, Chung CM, Chang ML, Chen MY, Chang ST, Chu PH, Chen TH, Lin WY, Huang TJ, Lin YS. The Unraveled Link Between Antiviral Therapy and Heart Failure Hospitalization in Chronic Hepatitis C Virus Infection - A Nationwide Cohort Study. Circ J 2018; 82:1623-1631. [PMID: 29503408 DOI: 10.1253/circj.cj-17-1118] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Although hepatitis C virus (HCV) is a known risk factor for cardiovascular disease, whether antiviral therapy (AVT) can reduce heart failure (HF) hospitalizations is unknown. METHODS AND RESULTS In this population-based cohort study, we used data from the Taiwan National Health Insurance Research Database to evaluate the effect of interferon-based therapy (IBT) on cardiovascular events in patients with chronic HCV infection. Clinical outcomes evaluated included HF hospitalizations; a composite of acute myocardial infarction, ischemic stroke, and peripheral artery disease; all-cause death; and cardiovascular death. Of 83,229 eligible patients with chronic HCV infection, we compared 16,284 patients who received IBT with untreated subjects after propensity score matching. Patients who received IBT were less likely to be hospitalized for HF compared with untreated subjects (incidence density.ID, 0.9 vs. 1.5 events per 103person-years; hazard ratio.HR, 0.58; 95% confidence interval.CI, 0.42-0.79; P=0.001). Compared with untreated subjects, the treated group had significantly lower risk of composite vascular events (ID, 3.7 vs. 5.0 events per 103person-years; P<0.001), all-cause death (ID, 5.6 vs. 17.2 events per 103person-years; P<0.001), and cardiovascular death (ID, 0.2 vs. 0.6 events per 103person-years; P=0.001). CONCLUSIONS AVT for chronic HCV infection might offer protection against HF hospitalizations, critical vascular events, and cardiovascular death beyond known beneficial effects.
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Affiliation(s)
- Ming-Shyan Lin
- Department of Cardiology, Chang Gung Memorial Hospital
- Department of Cardiology, Heart Failure Center, Chang Gung Memorial Hospital
| | - Chang-Min Chung
- Department of Cardiology, Heart Failure Center, Chang Gung Memorial Hospital
| | - Ming-Ling Chang
- Liver Research Center and Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital
| | - Mei-Yen Chen
- College of Nursing & Graduate Institute of Nursing, Chang Gung University of Science and Technology
- Department of Nursing, Chang Gung University
| | - Shih-Tai Chang
- Department of Cardiology, Heart Failure Center, Chang Gung Memorial Hospital
| | - Pao-Hsien Chu
- Department of Cardiology, Heart Failure Center, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University
| | | | | | - Tung-Jung Huang
- Department of Pulmonary Disease and Critical Care, Chang Gung Memorial Hospital
| | - Yu-Sheng Lin
- Department of Cardiology, Heart Failure Center, Chang Gung Memorial Hospital
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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.
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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
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Abstract
Hepatitis C virus (HCV) is the most common blood-borne infection in the United States and is of concern in older adults. HCV infection is associated with not only hepatic but also extrahepatic comorbidities common to the aging patient including diabetes, kidney and cardiovascular diseases, and neurocognitive impairment. The effect of direct-acting antiviral agents to treat HCV on these outcomes is limited. This article summarizes the literature regarding the epidemiology and natural history of HCV infection; the impact of age on clinical outcomes in HCV-infected persons; and current knowledge regarding safety and efficacy of HCV treatment regimens in the older patient.
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Affiliation(s)
- Michael Reid
- Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94122, USA
| | - Jennifer C Price
- Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94122, USA
| | - Phyllis C Tien
- Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94122, USA; Medical Service, Department of Veteran Affairs Medical Center, San Francisco, CA 94121, USA.
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Al-Rabadi L, Box T, Singhania G, Al-Marji C, Agarwal A, Hall I, Gordon CE, Tran H. Rationale for treatment of hepatitis C virus infection in end-stage renal disease patients who are not kidney transplant candidates. Hemodial Int 2018; 22 Suppl 1:S45-S52. [DOI: 10.1111/hdi.12656] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Laith Al-Rabadi
- Renal Section, Department of Medicine; University of Utah Hospital; Salt Lake City Utah USA
| | - Terry Box
- Gastroenterology Section, Department of Medicine; University of Utah Hospital; Salt Lake City Utah USA
| | - Girish Singhania
- Renal Section, Department of Medicine; University of Utah Hospital; Salt Lake City Utah USA
| | - Catreena Al-Marji
- Renal Section, Department of Medicine; University of Utah Hospital; Salt Lake City Utah USA
| | - Adhish Agarwal
- Renal Section, Department of Medicine; University of Utah Hospital; Salt Lake City Utah USA
| | - Isaac Hall
- Renal Section, Department of Medicine; University of Utah Hospital; Salt Lake City Utah USA
| | - Craig E. Gordon
- Renal Section, Department of Medicine; Boston Medical Center; Boston Massachusetts USA
| | - Huy Tran
- Gastroenterology Section, Department of Medicine; University of Iowa Hospital and Clinics; Iowa City Iowa USA
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Ponziani FR, Miele L, Tortora A, Furnari M, Bodini G, Pompili M, Gasbarrini A, Giannini EG. Treatment of early stage chronic hepatitis C virus infection. Expert Rev Clin Pharmacol 2018; 11:519-524. [PMID: 29498556 DOI: 10.1080/17512433.2018.1447923] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Abstract
INTRODUCTION Treatment of Hepatitis C Virus (HCV) with direct acting antivirals (DAAs) is able to achieve the cure of infection in almost the totality of patients, independently of the characteristics of the individual and the virus, using short treatment schedules, and without the need of ribavirin. The high cost of DAAs is the main limiting factor for universal treatment of HCV. However, there is a strong evidence that treatment of infection at the early stage of disease may be the most rewarding approach. Areas covered: This review evaluates the aspects underlying the benefit of treating chronic HCV infection at the early stage of disease. It outlines the considerations that have to be taken into account when planning treatment in patients with HCV and minimal liver disease, assessing the positive reflex of viral eradication on several HCV-associated extra-hepatic conditions such as the risk of lymphoma, insulin-resistance and glycaemic control, and renal function. Lastly, it also covers the improvement of patients' quality of life and the pharmaco-economic aspects associated with early treatment. Expert commentary: Treatment of patients with HCV and minimal liver disease is associated with a beneficial, pleiotropic effect of viral eradication that goes beyond the simplistic consideration of the improvement in liver disease-related outcomes.
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Affiliation(s)
- Francesca Romana Ponziani
- a Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico "A. Gemelli" , Catholic University of Rome , Rome , Italy
| | - Luca Miele
- a Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico "A. Gemelli" , Catholic University of Rome , Rome , Italy
| | - Annalisa Tortora
- a Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico "A. Gemelli" , Catholic University of Rome , Rome , Italy
| | - Manuele Furnari
- b Gastroenterology Unit, Department of Internal Medicine , University of Genoa, IRCCS Ospedale Policlinico San Martino , Genoa , Italy
| | - Giorgia Bodini
- b Gastroenterology Unit, Department of Internal Medicine , University of Genoa, IRCCS Ospedale Policlinico San Martino , Genoa , Italy
| | - Maurizio Pompili
- a Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico "A. Gemelli" , Catholic University of Rome , Rome , Italy
| | - Antonio Gasbarrini
- a Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico "A. Gemelli" , Catholic University of Rome , Rome , Italy
| | - Edoardo Giovanni Giannini
- b Gastroenterology Unit, Department of Internal Medicine , University of Genoa, IRCCS Ospedale Policlinico San Martino , Genoa , Italy
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Lin MS, Chung CM, Lin WY, Wei KL, Wang J, Lee YY, Hu JH, Tung TH, Lin YS. Antiviral therapy reduces risk of haemorrhagic stroke in patients with HCV infection: a nationwide cohort study. Antivir Ther 2018; 23:43-52. [PMID: 28471350 DOI: 10.3851/imp3172] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/17/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND The tendency for haemorrhagic stroke in patients with chronic HCV infection has emerged recently but the finding may be confounded by comorbidities. Proving the causality between HCV infection and haemorrhagic stroke is mandatory. Our study was designed to investigate the incidence of intracranial haemorrhage in HCV-infected patients with and without treatment. METHODS In the 11-year and population-based retrospective study, we acquired data from the Taiwan National Health Insurance Research Database. The patients with major comorbidities were excluded and 97,198 HCV-infected patients were included for analysis. Treated and untreated cohorts were matched with propensity score to make the confounding factors in two groups comparable. Cox proportional hazard regression analysis was performed to evaluate the hazard ratio of haemorrhagic stroke in the cohorts. We applied survival analysis to compare the cumulative incidence of outcome events between the two cohorts. RESULTS After matching, the incidence density (ID) of haemorrhagic stroke in the untreated cohort is significantly higher than in the treated cohort (ID: 1.0 versus 0.6 events per 1,000 person-years; P=0.0014). The adjusted hazard ratio (aHR) of haemorrhagic stroke is significantly reduced in the treated group (P<0.05). Cumulative incidence of haemorrhagic stroke is significantly lower in the treated group than in the untreated group (P=0.013). CONCLUSIONS The study demonstrates that antiviral therapy significantly reduces the events of intracranial haemorrhage in HCV-infected patients and consolidates the novel concept that chronic HCV infection is a risk factor for haemorrhagic stroke.
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Affiliation(s)
- Ming-Shyan Lin
- Department of Cardiology, Department of Internal Medicine, Liver Research Center, Chang-Gung Memorial Hospital, Yunlin, Taiwan
| | - Chang-Min Chung
- Department of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Wey-Yil Lin
- Department of Neurology and Neuroscience Research Center, Chang Gung Memorial Hospital, and Chang Gung University, Linkou, Taiwan
| | - Kuo-Liang Wei
- Department of Hepato-Gastroenterology and Liver Research Center, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Jui Wang
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Ying-Ying Lee
- Department of Neurology, Landseed Hospital, Taoyuan, Taiwan
| | - Jing-Hong Hu
- Department of Hepato-Gastroenterology and Liver Research Center, Chang Gung Memorial Hospital, Yunlin, Taiwan
| | - Tao-Hsin Tung
- Department of Medical Research and Education, Cheng Hsin General Hospital, Taipei, Taiwan
- Department of Public Health, School of Medicine, Fu-Jen Catholic University, Taipei, Taiwan
| | - Yu-Sheng Lin
- Department of Neurology and Neuroscience Research Center, Chang Gung Memorial Hospital, and Chang Gung University, Linkou, Taiwan
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Vassalle C, Petta S, Pepe A, Craxi A, Bondin M, Cacoub P. Expert opinion on managing chronic HCV in patients with cardiovascular disease. Antivir Ther 2018; 23:35-46. [PMID: 30451152 DOI: 10.3851/imp3248] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/21/2018] [Indexed: 02/07/2023]
Abstract
Extrahepatic manifestations of chronic HCV infection include cardiovascular diseases and an increase in cardiovascular mortality. The pathogenic mechanisms by which HCV contributes to cardiovascular disease are not well defined, however, it is likely that systemic inflammation, and the promotion of other metabolic diseases are involved. In this Review, the evidence for HCV infection as a non-traditional risk factor for cardiovascular disease is evaluated. Furthermore, practical advice to evaluate cardiovascular disease risk and disease in chronic hepatitis C patients are included for help in daily clinical practice. Despite the advances in therapies for the treatment of HCV, there remains a need for increased awareness among specialists so that patients are more likely to obtain the treatment required to mitigate disease progression.
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Affiliation(s)
- Cristina Vassalle
- Laboratory Medicine Unit, Fondazione CNR-Regione Toscana G Monasterio, Pisa, Italy
| | - Salvatore Petta
- Section of Gastroenterology and Hepatology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy
| | - Alessia Pepe
- MRI Unit, Fondazione CNR-Regione Toscana G Monasterio, Pisa, Italy
| | - Antonio Craxi
- Section of Gastroenterology and Hepatology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy
| | | | - 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
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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: 67] [Impact Index Per Article: 8.4] [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.
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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:
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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.
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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
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