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Johar D, Bedair El-Assal AH, Abou-El-Makarem MM, Hammouda EFA, Hegazy MS, Zaky S. Do oxidized low-density lipoproteins link to extra hepatic manifestations in chronic, non-cirrhotic HCV patients? Metabol Open 2025; 25:100339. [PMID: 39790936 PMCID: PMC11714377 DOI: 10.1016/j.metop.2024.100339] [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: 10/28/2024] [Revised: 12/07/2024] [Accepted: 12/09/2024] [Indexed: 01/12/2025] Open
Abstract
Background Tissue damage by viral hepatitis is a major cause of morbidity and mortality worldwide. Oxidation reactions and reactive oxygen species (ROS) transform proteins and lipids in plasma low-density lipoproteins (LDL) into the abnormal oxidized LDL (ox-LDL). Hepatitis C virus (HCV) infection induces oxidative/nitrosative stress from multiple sources, including the inducible nitric oxide synthase (iNOS), the mitochondrial electron transport chain, hepatocyte NAD(P)H oxidases (NOX enzymes), and inflammation. Further, HCV decreases reduced glutathione (GSH) synthesis and regeneration. Design Cross-section. Objective to quantify ox-LDL in serum of chronic non-cirrhotic HCV patients, and to assess ox-LDL association with HCV-induced extra hepatic manifestations. Patients and methods Twenty chronic, non-cirrhotic HCV female patients with extra hepatic manifestations, twenty chronic, non-cirrhotic female HCV patients without extra hepatic manifestations and twenty healthy age, sex matched controls. Methods Serum was used for determination of liver function tests, ox-LDL and the extracellular antioxidant enzyme Superoxide Dismutase EC CuZn-SOD. Results Patients with extra hepatic manifestations had statistically higher ox-LDL (76.63 ± 6.86 μg/L) than patients without extra hepatic manifestations (63.05 ± 6.6 μg/L) p < 0.001, and both patient groups had higher ox-LDL levels than the control group (44.1 ± 4.1 μg/L) p < 0.001. EC CuZn-SOD correlated negatively with ox-LDL in HCV patients with extra hepatic manifestation only. Conclusion Extra hepatic manifestations were not risk for anthropometric changes seen with HCV infection. Extra hepatic manifestations were associated with high serum ox-LDL. High serum levels of ox-LDL associated with- or were due to deregulated expression of serum EC CuZn-SOD in chronic HCV patients.
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Affiliation(s)
- Dina Johar
- Department of Biochemistry and Nutrition, Faculty of Women for Arts, Sciences and Education, Ain Shams University, Heliopolis, Cairo, Egypt
| | | | | | | | - Mohamed Soliman Hegazy
- Hepatogastroenterology and Infectious Diseases Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Samy Zaky
- Hepatogastroenterology and Infectious Diseases Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
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Wang S, Sun W, Cheng Y, Wang L, Ma S, Jing F, Zhang X, Zhou X. Relationship between plasma 12,13-diHOME level and nonalcoholic fatty liver disease in patients with type 2 diabetes and obesity. Minerva Endocrinol (Torino) 2025; 50:72-83. [PMID: 33855386 DOI: 10.23736/s2724-6507.21.03424-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) was one of the newly found lipokines. The goal of this study was to investigate whether the 12,13-diHOME was associated with related metabolic markers of nonalcoholic fatty liver disease (NAFLD) in a Chinese population with type 2 diabetes (T2DM) and obesity. METHODS This cross-sectional study enrolled 202 subjects with T2DM. Anthropometric parameters, 12,13-diHOME, serum lipids levels, fasting blood-glucose (FBG), serum glycosylated hemoglobin (HbA1c), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), liver and kidney function parameters were collected. NAFLD was diagnosed based on abdominal ultrasonography examination results. A computer-aided ultrasound quantitative method was applied to evaluate the liver fat content (LFC). RESULTS The number of the patients with fatty liver was 139 (68.81%) and those with non-fatty liver was 63 (31.19%). Subjects with NAFLD had a higher body mass index (BMI), diastolic blood pressure, serum alanine aminotransferase (ALT), triglyceride (TG), HOMA-IR, LFC, P<0.05 for all. But no significant difference was found in plasma 12,13-diHOME level (P=0.967), though its level trend was higher in non-NAFLD group. Plasma 12,13-diHOME was positively correlated with aspartate aminotransferase (AST), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), blood urea nitrogen (BUN), free fatty acid (FFA), C-peptide, FINS and HOMA-IR. It was negatively correlated with height, body weight, glomerular filtration rate (eGFR) and HbA1c. CONCLUSIONS Although 12,13-diHOME was correlated with AST, TC, HDL-C, BUN, FFA, C-peptide, FINS, HOMA-IR, eGFR and HbA1c, there was no significant difference in 12,13-diHOME level between the two groups. However, more research should be carried on about this newly-found lipokine.
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Affiliation(s)
- Sichao Wang
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, China
| | - Weixia Sun
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Yiping Cheng
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Lei Wang
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Shizhan Ma
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Fei Jing
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Xiujuan Zhang
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Xinli Zhou
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China -
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Huang YT, Hsu YC, Yang HI, Lee MH, Lai TH, Chen CJ, Huang YT. Causal Mediation Analyses for the Natural Course of Hepatitis C: A Prospective Cohort Study. J Epidemiol 2025; 35:21-29. [PMID: 39098040 PMCID: PMC11637814 DOI: 10.2188/jea.je20240034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 05/12/2024] [Indexed: 08/06/2024] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a systemic disease. However, the relative contribution of intrahepatic and extrahepatic diseases to mediating HCV-induced mortality is unclear, albeit critical in resource allocation for reducing preventable deaths. To this end, this study comprehensively quantified the extent to which intrahepatic and extrahepatic diseases mediate HCV-induced mortality. METHODS A community-based cohort study with >25 years of follow-up was conducted in Taiwan. HCV infection was profiled by antibodies against HCV and HCV RNA in participants' serum samples. The cohort data were linked to Taiwan's National Health Insurance Research Database to determine the incidences of potential mediating diseases and mortality. We employed causal mediation analyses to estimate the mediation effects of HCV on mortality in relation to the incidences of 34 candidate diseases. RESULTS In 18,972 participants with 934 HCV infection, we observed that 54.1% of HCV-induced mortality was mediated by intrahepatic diseases, such as liver cirrhosis and liver cancer, and 45.9% of mortality was mediated by extrahepatic diseases. The major extrahepatic mediating diseases included septicemia (estimated proportion of HCV-induced mortality mediated through the disease: 25.2%), renal disease (16.7%), blood/immune diseases (12.2%), gallbladder diseases (9.7%), and endocrine diseases (9.6%). In women, hypertension (20.0%), metabolic syndrome (18.9%), and type 2 diabetes (17.0%) also mediated HCV-induced mortality. A dose-response relationship of HCV viral load was further demonstrated for the mediation effect. CONCLUSION Both intrahepatic and extrahepatic manifestations mediated approximately half of HCV-induced mortality. The mediation mechanisms are supported by a dose-response relationship of HCV viral load.
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Affiliation(s)
- Yi-Ting Huang
- Institute of Statistical Science, Academia Sinica, Taipei, Taiwan
- Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan
| | - Yao-Chun Hsu
- Center for Liver Diseases, E-Da Hospital, Kaohsiung, Taiwan
- School of Medicine, I-Shou University, Kaohsiung, Taiwan
- Department of Medicine, Fu-Jen Catholic University Hospital, New Taipei, Taiwan
- Institute of Biomedical Informatics, Yangming Campus, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
- Institute of Clinical Medicine, Yangming Campus, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Biomedical Translation Research Center, Academia Sinica, Taipei, Taiwan
| | - Mei-Hsuan Lee
- Institute of Clinical Medicine, Yangming Campus, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Tai-Hsuan Lai
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chien-Jen Chen
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Yen-Tsung Huang
- Institute of Statistical Science, Academia Sinica, Taipei, Taiwan
- Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan
- Department of Mathematics, National Taiwan University, Taipei, Taiwan
- Department of Applied Mathematics, National Sun Yat-sen University, Kaohsiung, Taiwan
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Tani J, Masaki T, Oura K, Tadokoro T, Morishita A, Kobara H. Extrahepatic Cancer Risk in Patients with Hepatitis C Virus Infection Treated with Direct-Acting Antivirals. Microorganisms 2024; 12:1926. [PMID: 39338599 PMCID: PMC11434491 DOI: 10.3390/microorganisms12091926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2024] [Revised: 09/17/2024] [Accepted: 09/20/2024] [Indexed: 09/30/2024] Open
Abstract
Chronic hepatitis C virus (HCV) infection is associated with an increased risk of extrahepatic cancers, particularly non-Hodgkin lymphoma. The introduction of direct-acting antivirals (DAAs) has revolutionized HCV therapy, resulting in high cure rates. However, concerns have been raised about potential effects on cancer risk. This review summarizes the current evidence on extrahepatic cancer risk in HCV-infected patients treated with DAAs. We examined epidemiologic data on HCV-associated extrahepatic cancers and explored potential mechanisms linking HCV to carcinogenesis outside the liver. Studies evaluating cancer outcomes after DAA therapy were critically reviewed while considering methodological challenges. While some studies suggested a reduced risk of extrahepatic cancers after DAA therapy, others showed no significant change. Limitations included short follow-up periods and confounding variables. Immunological changes following rapid HCV clearance may have complex effects on cancer risk. Long-term prospective studies and mechanistic investigations are needed to fully elucidate the relationship between DAA therapy and extrahepatic cancer risk in HCV patients. Clinicians should remain vigilant for extrahepatic malignancies in this population.
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Affiliation(s)
- Joji Tani
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Takamatsu 761-0793, Kagawa, Japan
| | - Tsutomu Masaki
- Kagawa Saiseikai Hospital, Takamatsu 761-8076, Kagawa, Japan
| | - Kyoko Oura
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Takamatsu 761-0793, Kagawa, Japan
| | - Tomoko Tadokoro
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Takamatsu 761-0793, Kagawa, Japan
| | - Asahiro Morishita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Takamatsu 761-0793, Kagawa, Japan
| | - Hideki Kobara
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Takamatsu 761-0793, Kagawa, Japan
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Clarke M, Falcione S, Boghozian R, Todoran R, Zhang Y, C. Real MG, StPierre A, Joy T, Jickling GC. Viral Infection and Ischemic Stroke: Emerging Trends and Mechanistic Insights. J Am Heart Assoc 2024; 13:e035892. [PMID: 39258541 PMCID: PMC11935600 DOI: 10.1161/jaha.124.035892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Accepted: 07/22/2024] [Indexed: 09/12/2024]
Abstract
Population studies have suggested that viral infections may be contributing to risk of ischemic stroke, although the mechanisms for this are unclear. In this review, we examine the epidemiological evidence supporting the involvement of viral diseases, including influenza, COVID-19, chronic herpesvirus infections, and hepatitis C in current trends of stroke incidence. To support these associations, we highlight the virus-host interactions that are critical in the context of stroke, including direct effects of acute and persistent viral infections on vascular function, inflammation, and thrombosis. Additionally, we evaluate the systemic changes that occur during viral infection that can predispose individuals to ischemic stroke, including alterations in blood pressure regulation, coagulation, and lipid metabolism. Our review emphasizes the need to further elucidate precise mechanisms involved in viral infections and stroke risk. Future research will inform the development of targeted interventions for stroke prevention in the context of viral diseases.
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Affiliation(s)
- Michael Clarke
- Faculty of Medicine and DentistryDepartment of Medical Microbiology and ImmunologyUniversity of AlbertaEdmontonABCanada
| | - Sarina Falcione
- Faculty of Medicine and DentistryDepartment of MedicineDivision of NeurologyUniversity of AlbertaEdmontonABCanada
| | - Roobina Boghozian
- Faculty of Medicine and DentistryDepartment of MedicineDivision of NeurologyUniversity of AlbertaEdmontonABCanada
| | - Raluca Todoran
- Faculty of Medicine and DentistryDepartment of MedicineDivision of NeurologyUniversity of AlbertaEdmontonABCanada
| | - Yiran Zhang
- Faculty of Medicine and DentistryDepartment of MedicineDivision of NeurologyUniversity of AlbertaEdmontonABCanada
| | - Maria Guadalupe C. Real
- Faculty of Medicine and DentistryDepartment of MedicineDivision of NeurologyUniversity of AlbertaEdmontonABCanada
| | - Alexis StPierre
- Faculty of Medicine and DentistryDepartment of MedicineDivision of NeurologyUniversity of AlbertaEdmontonABCanada
| | - Twinkle Joy
- Faculty of Medicine and DentistryDepartment of MedicineDivision of NeurologyUniversity of AlbertaEdmontonABCanada
| | - Glen C. Jickling
- Faculty of Medicine and DentistryDepartment of Medical Microbiology and ImmunologyUniversity of AlbertaEdmontonABCanada
- Faculty of Medicine and DentistryDepartment of MedicineDivision of NeurologyUniversity of AlbertaEdmontonABCanada
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Durazzo TC, Kraybill EP, Stephens LH, May AC, Meyerhoff DJ. Pro-atherogenic medical conditions are associated with widespread regional brain metabolite abnormalities in those with alcohol use disorder. Alcohol Alcohol 2024; 59:agae055. [PMID: 39127890 PMCID: PMC11316785 DOI: 10.1093/alcalc/agae055] [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: 05/15/2024] [Revised: 07/24/2024] [Accepted: 07/31/2024] [Indexed: 08/12/2024] Open
Abstract
AIMS Widespread brain metabolite abnormalities in those with alcohol use disorder (AUD) were reported in numerous studies, but the effects of the pro-atherogenic conditions of hypertension, type 2 diabetes mellitus, hepatitis C seropositivity, and hyperlipidemia on metabolite levels were not considered. These conditions were associated with brain metabolite abnormalities in those without AUD. We predicted treatment-seeking individuals with AUD and pro-atherogenic conditions (Atherogenic+) demonstrate lower regional metabolite markers of neuronal viability [N-acetylaspartate (NAA)] and cell membrane turnover/synthesis [choline-containing compounds (Cho)], compared with those with AUD without pro-atherogenic conditions (Atherogenic-) and healthy controls (CON). METHODS Atherogenic+ (n = 59) and Atherogenic- (n = 51) and CON (n = 49) completed a 1.5 T proton magnetic resonance spectroscopic imaging study. Groups were compared on NAA, Cho, total creatine, and myoinositol in cortical gray matter (GM), white matter (WM), and select subcortical regions. RESULTS Atherogenic+ had lower frontal GM and temporal WM NAA than CON. Atherogenic+ showed lower parietal GM, frontal, parietal and occipital WM and lenticular nuclei NAA level than Atherogenic- and CON. Atherogenic- showed lower frontal GM and WM NAA than CON. Atherogenic+ had lower Cho level than CON in the frontal GM, parietal WM, and thalamus. Atherogenic+ showed lower frontal WM and cerebellar vermis Cho than Atherogenic- and CON. CONCLUSIONS Findings suggest proatherogenic conditions in those with AUD were associated with increased compromise of neuronal integrity and cell membrane turnover/synthesis. The greater metabolite abnormalities observed in Atherogenic+ may relate to increased oxidative stress-related compromise of neuronal and glial cell structure and/or impaired arterial vasoreactivity/lumen viability.
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Affiliation(s)
- Timothy C Durazzo
- Mental Illness Research and Education Clinical Centers, VA Palo Alto Health Care System, 3801 Miranda Ave. (151Y), Palo Alto, CA 94304, United States
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA 94305, United States
| | - Eric P Kraybill
- Mental Illness Research and Education Clinical Centers, VA Palo Alto Health Care System, 3801 Miranda Ave. (151Y), Palo Alto, CA 94304, United States
| | - Lauren H Stephens
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA 94305, United States
| | - April C May
- Mental Illness Research and Education Clinical Centers, VA Palo Alto Health Care System, 3801 Miranda Ave. (151Y), Palo Alto, CA 94304, United States
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA 94305, United States
| | - Dieter J Meyerhoff
- Center for Imaging of Neurodegenerative Diseases (CIND), San Francisco VA Medical Center, 4150 Clement St. (114M) San Francisco, CA 94121, United States
- Department of Radiology and Biomedical Imaging, University of California, 505 Parnassus St., San Francisco, CA 94143, United States
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Horbal SR, Belancourt PX, Zhang P, Holcombe SA, Saini S, Wang SC, Sales AE, Su GL. Independent Associations of Aortic Calcification with Cirrhosis and Liver Related Mortality in Veterans with Chronic Liver Disease. Dig Dis Sci 2024; 69:2681-2690. [PMID: 38653948 PMCID: PMC11258161 DOI: 10.1007/s10620-024-08450-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Accepted: 04/12/2024] [Indexed: 04/25/2024]
Abstract
INTRODUCTION Abdominal aortic calcifications (AAC) are incidentally found on medical imaging and useful cardiovascular burden approximations. The Morphomic Aortic Calcification Score (MAC) leverages automated deep learning methods to quantify and score AACs. While associations of AAC and non-alcoholic fatty liver disease (NAFLD) have been described, relationships of AAC with other liver diseases and clinical outcome are sparse. This study's purpose was to evaluate AAC and liver-related death in a cohort of Veterans with chronic liver disease (CLD). METHODS We utilized the VISN 10 CLD cohort, a regional cohort of Veterans with the three forms of CLD: NAFLD, hepatitis C (HCV), alcohol-associated (ETOH), seen between 2008 and 2014, with abdominal CT scans (n = 3604). Associations between MAC and cirrhosis development, liver decompensation, liver-related death, and overall death were evaluated with Cox proportional hazard models. RESULTS The full cohort demonstrated strong associations of MAC and cirrhosis after adjustment: HR 2.13 (95% CI 1.63, 2.78), decompensation HR 2.19 (95% CI 1.60, 3.02), liver-related death HR 2.13 (95% CI 1.46, 3.11), and overall death HR 1.47 (95% CI 1.27, 1.71). These associations seemed to be driven by the non-NAFLD groups for decompensation and liver-related death [HR 2.80 (95% CI 1.52, 5.17; HR 2.34 (95% CI 1.14, 4.83), respectively]. DISCUSSION MAC was strongly and independently associated with cirrhosis, liver decompensation, liver-related death, and overall death. Surprisingly, stratification results demonstrated comparable or stronger associations among those with non-NAFLD etiology. These findings suggest abdominal aortic calcification may predict liver disease severity and clinical outcomes in patients with CLD.
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Affiliation(s)
- Steven R Horbal
- Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
- Morphomics Analysis Group, University of Michigan, Ann Arbor, MI, USA.
| | | | - Peng Zhang
- Department of Surgery, University of Michigan, Ann Arbor, MI, USA
- Morphomics Analysis Group, University of Michigan, Ann Arbor, MI, USA
| | - Sven A Holcombe
- Department of Surgery, University of Michigan, Ann Arbor, MI, USA
- Morphomics Analysis Group, University of Michigan, Ann Arbor, MI, USA
| | - Sameer Saini
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
| | - Stewart C Wang
- Department of Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Anne E Sales
- VA Ann Arbor Healthcare System, Ann Arbor, MI, USA
- Sinclair School of Nursing and Department of Family and Community Medicine, University of Missouri, Colombia, MO, USA
| | - Grace L Su
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
- Gastroenterology Section, Ann Arbor VA Healthcare System, Ann Arbor, MI, USA
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Sharma H, Mossman K, Austin RC. Fatal attractions that trigger inflammation and drive atherosclerotic disease. Eur J Clin Invest 2024; 54:e14169. [PMID: 38287209 DOI: 10.1111/eci.14169] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 12/14/2023] [Accepted: 01/09/2024] [Indexed: 01/31/2024]
Abstract
BACKGROUND Atherosclerosis is the salient, underlying cause of cardiovascular diseases, such as arrhythmia, coronary artery disease, cardiomyopathy, pulmonary embolism and myocardial infarction. In recent years, atherosclerosis pathophysiology has evolved from a lipid-based to an inflammation-centric ideology. METHODS This narrative review is comprised of review and original articles that were found through the PubMed search engine. The following search terms or amalgamation of terms were used: "cardiovascular disease," "atherosclerosis," "inflammation," "GRP78," "Hsp60," "oxidative low-density lipoproteins," "aldehyde dehydrogenase," "β2-glycoprotein," "lipoprotein lipase A," "human cytomegalovirus." "SARS-CoV-2," "chlamydia pneumonia," "autophagy," "thrombosis" and "therapeutics." RESULTS Emerging evidence supports the concept that atherosclerosis is associated with the interaction between cell surface expression of stress response chaperones, including GRP78 and Hsp60, and their respective autoantibodies. Moreover, various other autoantigens and their autoantibodies have displayed a compelling connection with the development of atherosclerosis, including oxidative low-density lipoproteins, aldehyde dehydrogenase, β2-glycoprotein and lipoprotein lipase A. Atherosclerosis progression is also concurrent with viral and bacterial activators of various diseases. This narrative review will focus on the contributions of human cytomegalovirus as well as SARS-CoV-2 and chlamydia pneumonia in atherosclerosis development. Notably, the interaction of an autoantigen with their respective autoantibodies or the presence of a foreign antigen can enhance inflammation development, which leads to atherosclerotic lesion progression. CONCLUSION We will highlight and discuss the complex role of the interaction between autoantigens and autoantibodies, and the presence of foreign antigens in the development of atherosclerotic lesions in relationship to pro-inflammatory responses.
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Affiliation(s)
- Hitesh Sharma
- Division of Nephrology, Department of Medicine, McMaster University, The Research Institute of St. Joe's Hamilton and the Hamilton Centre for Kidney Research, Hamilton, Ontario, Canada
| | - Karen Mossman
- Department of Medicine, Michael DeGroote Institute for Infectious Disease Research and the McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada
| | - Richard C Austin
- Division of Nephrology, Department of Medicine, McMaster University, The Research Institute of St. Joe's Hamilton and the Hamilton Centre for Kidney Research, Hamilton, Ontario, Canada
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Cespiati A, Coelho Rodrigues I, Santos I, Policarpo S, Carvalhana S, Fracanzani AL, Cortez-Pinto H. Effect of HCV eradication by DAAs on liver steatosis, carotid atherosclerosis, and associated metabolic comorbidities: A systematic review. Liver Int 2024; 44:1075-1092. [PMID: 38385567 DOI: 10.1111/liv.15876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 12/11/2023] [Accepted: 02/08/2024] [Indexed: 02/23/2024]
Abstract
BACKGROUND AND AIMS The beneficial effect of Hepatitis C virus (HCV) eradication by direct antiviral agents (DAAs) on liver fibrosis is well defined. Despite this, the impact of viral eradication in both hepatic and extra-hepatic metabolic features is underreached. This systematic review aimed to synthesize the evidence on the impact of HCV eradication by DAAs on liver steatosis, carotid atherosclerosis, glucidic impairment, dyslipidaemia, and weight gain. METHODS A systematic search of the existing literature (up to December 2022) identified 97 original studies that fulfilled the inclusion criteria. RESULTS Whereas total cholesterol and low-density lipoprotein (LDL) seem to increase after viral eradication, the cardiovascular damage expressed as carotid plaques and intima-media thickness seems to improve. Otherwise, the effect on liver steatosis, glucidic homeostasis, and weight seems to be strictly dependent on the presence of baseline metabolic disorders. CONCLUSION Despite high heterogeneity and relatively short follow-up of included studies, we can conclude that the presence of metabolic risk factors should be strictly evaluated due to their impact on liver steatosis, glucidic and lipid homeostasis, and on weight gain to better identify patients at risk of liver disease progression despite the virus eradication.
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Affiliation(s)
- Annalisa Cespiati
- Unit of Medicine and Metabolic Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Inês Coelho Rodrigues
- Departamento de Gastrenterologia, Centro Hospitalar Universitário Lisboa Norte, Departamento de Dietética e Nutrição, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
| | - Inês Santos
- Laboratório de Nutrição, Faculdade de Medicina, Centro Académico de Medicina de Lisboa, Universidade de Lisboa, Lisbon, Portugal
- Faculdade de Medicina, Instituto de Saúde Ambiental (ISAMB), Universidade de Lisboa, Lisbon, Portugal
| | - Sara Policarpo
- Laboratório de Nutrição, Faculdade de Medicina, Centro Académico de Medicina de Lisboa, Universidade de Lisboa, Lisbon, Portugal
- Serviço de Dietética e Nutrição, Centro Hospitalar Universitário Lisboa Norte, E.P.E., Lisbon, Portugal
| | - Sofia Carvalhana
- Departamento de Gastrenterologia, Centro Hospitalar Universitário Lisboa Norte, Departamento de Dietética e Nutrição, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
- Clínica Universitária de Gastrenterologia, Laboratório de Nutrição, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Anna Ludovica Fracanzani
- Unit of Medicine and Metabolic Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Helena Cortez-Pinto
- Departamento de Gastrenterologia, Centro Hospitalar Universitário Lisboa Norte, Departamento de Dietética e Nutrição, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
- Clínica Universitária de Gastrenterologia, Laboratório de Nutrição, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
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Kadosh BS, Birs AS, Flattery E, Stachel M, Hong KN, Xia Y, Gidea C, Aslam S, Razzouk L, Saraon T, Goldberg R, Rao S, Pretorius V, Moazami N, Smith DE, Adler ED, Reyentovich A. Cardiac allograft vasculopathy in heart transplant recipients from hepatitis C viremic donors. Clin Transplant 2024; 38:e15294. [PMID: 38545881 DOI: 10.1111/ctr.15294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Revised: 02/19/2024] [Accepted: 03/08/2024] [Indexed: 04/20/2024]
Abstract
BACKGROUND Recent studies suggest the transplantation of Hepatitis C (HCV) hearts from viremic donors is associated with comparable 1 year survival to nonviremic donors. Though HCV viremia is a known risk factor for accelerated atherosclerosis, data on cardiac allograft vasculopathy (CAV) outcomes are limited. We compared the incidence of CAV in heart transplant recipients from HCV viremic donors (nucleic acid amplification test positive; NAT+) compared to non-HCV infected donors (NAT-). METHODS We retrospectively reviewed annual coronary angiograms with intravascular ultrasound from April 2017 to August 2020 at two large cardiac transplant centers. CAV was graded according to ISHLT guidelines. Maximal intimal thickness (MIT) ≥ 0.5 mm was considered significant for subclinical disease. RESULTS Among 270 heart transplant recipients (mean age 54; 77% male), 62 patients were transplanted from NAT+ donors. CAV ≥ grade 1 was present in 8.8% of the NAT+ versus 16.8% of the NAT- group at 1 year, 20% versus 28.8% at 2 years, and 33.3% versus 41.5% at 3 years. After adjusting for donor age, donor smoking history, recipient BMI, recipient, hypertension, and recipient diabetes, NAT+ status did not confer increased risk of CAV (HR.80; 95% CI.45-1.40, p = 0.43) or subclinical IVUS disease (HR.87; 95% CI.58-1.30, p = 0.49). Additionally, there was no difference in the presence of rapidly progressive lesions on IVUS. CONCLUSION Our data show that NAT+ donors conferred no increased risk for early CAV or subclinical IVUS disease following transplantation in a cohort of heart transplant patients who were treated for HCV, suggesting the short-term safety of this strategy to maximize the pool of available donor hearts.
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Affiliation(s)
- Bernard S Kadosh
- Leon H. Charney Division of Cardiology, NYU Langone Health, New York University Grossman School of Medicine, New York, New York, USA
| | - Antoinette S Birs
- Division of Cardiology, Department of Medicine, University of California San Diego, La Jolla, California, USA
| | - Erin Flattery
- Leon H. Charney Division of Cardiology, NYU Langone Health, New York University Grossman School of Medicine, New York, New York, USA
| | - Maxine Stachel
- Leon H. Charney Division of Cardiology, NYU Langone Health, New York University Grossman School of Medicine, New York, New York, USA
| | - Kimberly N Hong
- Division of Cardiology, Department of Medicine, University of California San Diego, La Jolla, California, USA
| | - Yuhe Xia
- Leon H. Charney Division of Cardiology, NYU Langone Health, New York University Grossman School of Medicine, New York, New York, USA
| | - Claudia Gidea
- Leon H. Charney Division of Cardiology, NYU Langone Health, New York University Grossman School of Medicine, New York, New York, USA
| | - Saima Aslam
- Division of Infectious Disease, Department of Medicine, University of California San Diego, La Jolla, California, USA
| | - Louai Razzouk
- Leon H. Charney Division of Cardiology, NYU Langone Health, New York University Grossman School of Medicine, New York, New York, USA
| | - Tajinderpal Saraon
- Leon H. Charney Division of Cardiology, NYU Langone Health, New York University Grossman School of Medicine, New York, New York, USA
| | - Randal Goldberg
- Leon H. Charney Division of Cardiology, NYU Langone Health, New York University Grossman School of Medicine, New York, New York, USA
| | - Shaline Rao
- Leon H. Charney Division of Cardiology, NYU Langone Health, New York University Grossman School of Medicine, New York, New York, USA
| | - Victor Pretorius
- Department of Cardiothoracic Surgery, University of California San Diego, La Jolla, California, USA
| | - Nader Moazami
- Department of Cardiothoracic Surgery, NYU Langone Health, New York University Grossman School of Medicine, New York, New York, USA
| | - Deane E Smith
- Department of Cardiothoracic Surgery, NYU Langone Health, New York University Grossman School of Medicine, New York, New York, USA
| | - Eric D Adler
- Division of Cardiology, Department of Medicine, University of California San Diego, La Jolla, California, USA
| | - Alex Reyentovich
- Leon H. Charney Division of Cardiology, NYU Langone Health, New York University Grossman School of Medicine, New York, New York, USA
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Pascual-Oliver A, Casas-Deza D, Yagüe-Caballero C, Arbones-Mainar JM, Bernal-Monterde V. Lipid Profile and Cardiovascular Risk Modification after Hepatitis C Virus Eradication. Pathogens 2024; 13:278. [PMID: 38668233 PMCID: PMC11054742 DOI: 10.3390/pathogens13040278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 03/18/2024] [Accepted: 03/21/2024] [Indexed: 04/29/2024] Open
Abstract
The eradication of the hepatitis C virus (HCV) has revolutionized the hepatology paradigm, halting the progression of advanced liver disease in patients with chronic infection and reducing the risk of hepatocarcinoma. In addition, treatment with direct-acting antivirals can reverse the lipid and carbohydrate abnormalities described in HCV patients. Although HCV eradication may reduce the overall risk of vascular events, it is uncertain whether altered lipid profiles increase the risk of cerebrovascular disease in certain patients. We have conducted a review on HCV and lipid and carbohydrate metabolism, as well as new scientific advances, following the advent of direct-acting antivirals.
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Affiliation(s)
- Andrea Pascual-Oliver
- Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; (A.P.-O.); (C.Y.-C.); (V.B.-M.)
| | - Diego Casas-Deza
- Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; (A.P.-O.); (C.Y.-C.); (V.B.-M.)
- Adipocyte and Fat Biology Laboratory (AdipoFat), Translational Research Unit, University Hospital Miguel Servet, 50009 Zaragoza, Spain;
- Instituto Aragones de Ciencias de la Salud (IACS), 50009 Zaragoza, Spain
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain
| | - Carmen Yagüe-Caballero
- Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; (A.P.-O.); (C.Y.-C.); (V.B.-M.)
- Adipocyte and Fat Biology Laboratory (AdipoFat), Translational Research Unit, University Hospital Miguel Servet, 50009 Zaragoza, Spain;
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain
| | - Jose M. Arbones-Mainar
- Adipocyte and Fat Biology Laboratory (AdipoFat), Translational Research Unit, University Hospital Miguel Servet, 50009 Zaragoza, Spain;
- Instituto Aragones de Ciencias de la Salud (IACS), 50009 Zaragoza, Spain
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain
- CIBER Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto Salud Carlos III, 28029 Madrid, Spain
| | - Vanesa Bernal-Monterde
- Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; (A.P.-O.); (C.Y.-C.); (V.B.-M.)
- Adipocyte and Fat Biology Laboratory (AdipoFat), Translational Research Unit, University Hospital Miguel Servet, 50009 Zaragoza, Spain;
- Instituto Aragones de Ciencias de la Salud (IACS), 50009 Zaragoza, Spain
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain
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Laabidi S, Medhioub M, Khsiba A, Bach Ali A, Ben Mohamed A, Hamzaoui L. Impact des antiviraux à action directe sur l'athérosclérose subclinique chez les patients atteints d’une hépatite C chronique. LA TUNISIE MEDICALE 2024; 102:170-175. [PMID: 38545713 PMCID: PMC11358770 DOI: 10.62438/tunismed.v102i3.4601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Accepted: 02/06/2024] [Indexed: 09/14/2024]
Abstract
INTRODUCTION The impact of direct antiviral drugs (DAAs) on extrahepatic manifestations in chronic hepatitis C (CHC) has been poorly studied. AIM To assess the prevalence of subclinical atherosclerosis in patients with CHC and the impact of DAAs on atherosclerotic lesions. Methods A 5-year prospective evaluative study, including patients followed for CHC at hepato-gastroenterology department. The subclinical atherosclerosis was assessed by ultrasound measurement of carotid intima-media thickness (IMTc) and the highest IMTc measurements from the left and right side defined the IMTc maximum (IMTc max). IMTc>75th percentile (IMTc75) define subclinical atherosclerosis with high cardiovascular risk. Patients were evaluated before (T0) and one year after DAAs therapy achievement (T1). RESULTS At time T0, forty patients (median age: 55 y.; sex ratio M / F = 0.48), were included. Average value of IMTc max was 0.68 ± 0.16 mm. Subclinical atherosclerosis was noted in 82.5 %. At time T1, 28 patients were evaluated, all of whom completed sustained virological response (SVR). Compared to time T0, there was a significant increase in cholesterol (p = 0.001) and triglyceride (p = 0.009) levels. IMTc max was significantly higher at time T1 compared to T0 (0.75 Vs 0.67 mm, p = 0.04). Prevalence of IMTc75 was 82.1% at time T0 and 75% at time T1 (p=0.5). CONCLUSIONS SVR, in CHC patients treated with DAA, was associated with worsening of carotid atherosclerotic lesions.
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Affiliation(s)
- Sarra Laabidi
- Gastroenterology department Mohamed Taher Maamouri Hospital, Nabeul, Tunisia
| | - Mouna Medhioub
- Gastroenterology department Mohamed Taher Maamouri Hospital, Nabeul, Tunisia
| | - Amal Khsiba
- Gastroenterology department Mohamed Taher Maamouri Hospital, Nabeul, Tunisia
| | - Asma Bach Ali
- Biology department Mohamed Taher Maamouri Hospital, Nabeul, Tunisia
| | - Asma Ben Mohamed
- Gastroenterology department Mohamed Taher Maamouri Hospital, Nabeul, Tunisia
| | - Lamine Hamzaoui
- Gastroenterology department Mohamed Taher Maamouri Hospital, Nabeul, Tunisia
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Jaiswal V, Ang SP, Hanif M, Jha M, Kumar V, Siddiq A, Vachhani B, Halder A, Koifman M, Jeanty H, Soni S, Subhan Waleed M, Kumar T, Huang H, Bandyopadhyay D. Cardioprotective effect of antiviral therapy among hepatitis C infected patients: A meta-analysis. IJC HEART & VASCULATURE 2023; 49:101270. [PMID: 37766883 PMCID: PMC10520301 DOI: 10.1016/j.ijcha.2023.101270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 08/07/2023] [Accepted: 09/08/2023] [Indexed: 09/29/2023]
Abstract
Background Hepatitis C (HCV) infections have been shown to be associated a with higher risk of atherosclerotic cardiovascular disease (CVD). However, the use of antiviral therapy (AVT) and the risk of CVD has not been well established with limited literature. Objective We sought to evaluate the association between AVT use post-HCV infection and cardiovascular outcomes. Methods We performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until 10th March 2023. Primary clinical outcomes were the incidence of any CVD. Secondary endpoints were all-cause of mortality, stroke, myocardial infarction, and peripheral artery disease. Results A total of 394,452 patients were included in the analysis (111,076 in the AVT group and 283,376 patients in the NAVT group). The mean age of patients among AVT and NAVT groups was comparable (58.7 vs 58.18). The pooled analysis of primary outcomes showed that AVT was associated with a significantly reduced risk of any CVD (HR, 0.55(95%CI: 0.41-0.75), P < 0.001) compared with the NAVT group of patients. Secondary outcomes including ACM (HR, 0.38(95%CI: 0.32-0.46), P < 0.001), MI (HR, 0.62(95%CI: 0.41-0.94), P = 0.02), and PAD (HR, 0.62(95%CI: 0.41-0.93), P = 0.02) were significantly lower among AVT groups compared with NAVT groups of patients with HCV infection. However, the risk of stroke was comparable between both groups of patients (HR, 0.79(95%CI: 0.58-1.07), P = 0.13). Conclusion Our analysis shows HCV-infected patients post-AVT have a significantly lower risk of any CVD, MI, ACM, and PAD compared with NAVT groups of patients.
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Affiliation(s)
- Vikash Jaiswal
- Department of Research, Larkin Community Hospital, USA
- JCCR Cardiology Research, Varanasi, India
| | - Song Peng Ang
- Department of Internal Medicine, Rutgers Health/Community Medical Center, NJ, USA
| | - Muhammad Hanif
- Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, NY, USA
| | - Mayank Jha
- Department of Research, Larkin Community Hospital, USA
- Department of Medicine and Surgery, Government Medical College, Surat, India
| | - Vikash Kumar
- Department of Internal Medicine, The Brooklyn Hospital Center, NY, USA
| | | | | | - Anupam Halder
- Department of Internal Medicine, UPMC Harrisburg, PA, USA
| | - Michelle Koifman
- Department of Internal Medicine, The Brooklyn Hospital Center, NY, USA
| | - Herby Jeanty
- Department of Internal Medicine, The Brooklyn Hospital Center, NY, USA
| | - Siddharath Soni
- Shree Narayan Medical Institute and Hospital, Saharsa, Bihar, India
| | | | - Tushar Kumar
- Department of Radiology, Sikkim Manipal Institute of Medical Science, Gangtok, India
| | - Helen Huang
- RCSI University of Medicine and Health Sciences, Dublin, Ireland
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Weng MT, Chang TH, Lin CC, Wu CS. Rheumatic manifestations of hepatitis C virus infection are associated with autoantibodies but not viremia. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2023; 56:739-746. [PMID: 37055257 DOI: 10.1016/j.jmii.2023.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 02/22/2023] [Accepted: 03/23/2023] [Indexed: 04/03/2023]
Abstract
BACKGROUND To investigate the associations between extrahepatic manifestations, autoantibodies, and viremia in patients with hepatitis C virus (HCV) infection. METHODS This cross-sectional study recruited patients with HCV infection from the outpatient department of a tertiary medical center in Northern Taiwan between January 2017 and August 2019. Autoantibody profiles and the clinical parameters of HCV infection were evaluated using laboratory tests, and a questionnaire was used to record extrahepatic manifestations. HCV infection status, including inactive HCV infection, active hepatitis, and cirrhosis, was defined according to abdominal ultrasonography findings and alanine transaminase levels. RESULTS A total of 77 patients with HCV were recruited, with 19.5% and 16.9% of patients, respectively, presenting with arthritis and dry eyes. Autoantibody screening revealed rheumatoid factor (RF), antinuclear antibody (ANA), anti-Ro antibody, and anti-La antibody positivity in 20.8%, 23.4%, 13.0%, and 2.6% of the patients, respectively. The presence of RF was associated with arthritis, whereas the presence of ANA was associated with dry eyes but not dry mouth. Active hepatitis and HCV-related cirrhosis were associated with viremia, but not autoantibody profiles. CONCLUSION In this single-center study, the prevalence of extrahepatic manifestations and autoantibodies did not differ in patients stratified by the HCV infection status. Rheumatic manifestations were associated with the presence of autoantibodies but not with viremia.
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Affiliation(s)
- Meng-Tzu Weng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Hsin-Chu Branch, Hsinchu, Taiwan.
| | - Ting-Hui Chang
- Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
| | - Chien-Chu Lin
- Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
| | - Chien-Sheng Wu
- Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
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15
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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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Lopez-Delgado JC, Putzu A, Landoni G. The importance of liver function assessment before cardiac surgery: A narrative review. Front Surg 2022; 9:1053019. [PMID: 36561575 PMCID: PMC9764862 DOI: 10.3389/fsurg.2022.1053019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Accepted: 11/15/2022] [Indexed: 12/12/2022] Open
Abstract
The demand for cardiac surgery procedures is increasing globally. Thanks to an improvement in survival driven by medical advances, patients with liver disease undergo cardiac surgery more often. Liver disease is associated with the development of heart failure, especially in patients with advanced cirrhosis. Cardiovascular risk factors can also contribute to the development of both cardiomyopathy and liver disease and heart failure itself can worsen liver function. Despite the risk that liver disease and cirrhosis represent for the perioperative management of patients who undergo cardiac surgery, liver function is often not included in common risk scores for preoperative evaluation. These patients have worse short and long-term survival when compared with other cardiac surgery populations. Preoperative evaluation of liver function, postoperative management and close postoperative follow-up are crucial for avoiding complications and improving results. In the present narrative review, we discuss the pathophysiological components related with postoperative complications and mortality in patients with liver disease who undergo cardiac surgery and provide recommendations for the perioperative management.
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Affiliation(s)
- Juan C. Lopez-Delgado
- Hospital Clinic de Barcelona, Area de Vigilancia Intensiva (ICMiD), Barcelona, Spain,IDIBELL (Institut d’Investigació Biomèdica Bellvitge; Biomedical Investigation Institute of Bellvitge), L’Hospitalet de Llobregat, Barcelona, Spain,Correspondence: Juan C. Lopez-Delgado Alessandro Putzu
| | - Alessandro Putzu
- Division of Anesthesiology, Department of Acute Medicine, Geneva University Hospitals, Geneva, Switzerland,Correspondence: Juan C. Lopez-Delgado Alessandro Putzu
| | - Giovanni Landoni
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy,Vita-Salute San Raffaele University, Milan, Italy
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Zhou H, Astore C, Skolnick J. PHEVIR: an artificial intelligence algorithm that predicts the molecular role of pathogens in complex human diseases. Sci Rep 2022; 12:20889. [PMID: 36463386 PMCID: PMC9719543 DOI: 10.1038/s41598-022-25412-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 11/29/2022] [Indexed: 12/04/2022] Open
Abstract
Infectious diseases are known to cause a wide variety of post-infection complications. However, it's been challenging to identify which diseases are most associated with a given pathogen infection. Using the recently developed LeMeDISCO approach that predicts comorbid diseases associated with a given set of putative mode of action (MOA) proteins and pathogen-human protein interactomes, we developed PHEVIR, an algorithm which predicts the corresponding human disease comorbidities of 312 viruses and 57 bacteria. These predictions provide an understanding of the molecular bases of complications and means of identifying appropriate drug targets to treat them. As an illustration of its power, PHEVIR is applied to identify putative driver pathogens and corresponding human MOA proteins for Type 2 diabetes, atherosclerosis, Alzheimer's disease, and inflammatory bowel disease. Additionally, we explore the origins of the oncogenicity/oncolyticity of certain pathogens and the relationship between heart disease and influenza. The full PHEVIR database is available at https://sites.gatech.edu/cssb/phevir/ .
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Affiliation(s)
- Hongyi Zhou
- Center for the Study of Systems Biology, School of Biological Sciences, Georgia Institute of Technology, 950 Atlantic Drive, N.W., Atlanta, GA, 30332, USA
| | - Courtney Astore
- Center for the Study of Systems Biology, School of Biological Sciences, Georgia Institute of Technology, 950 Atlantic Drive, N.W., Atlanta, GA, 30332, USA
| | - Jeffrey Skolnick
- Center for the Study of Systems Biology, School of Biological Sciences, Georgia Institute of Technology, 950 Atlantic Drive, N.W., Atlanta, GA, 30332, USA.
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Ramadan MS, Boccia F, Moretto SM, De Gregorio F, Gagliardi M, Iossa D, Durante-Mangoni E, Zampino R. Cardiovascular Risk in Patients with Chronic Hepatitis C Treated with Direct Acting Antivirals. J Clin Med 2022; 11:5781. [PMID: 36233646 PMCID: PMC9572655 DOI: 10.3390/jcm11195781] [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: 08/31/2022] [Revised: 09/23/2022] [Accepted: 09/26/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Chronic hepatitis C (CHC) is associated with hepatic and extrahepatic complications, including cardiovascular disease (CVD). The effects of sustained virological response (SVR) and liver fibrosis on CVD risk are not well established. Aims: We aim to assess the dynamics of Fibrosis-4 (FIB-4) and Atherosclerotic Cardiovascular Disease 2013 (ASCVD) scores up to three years after direct acting antivirals (DAA) treatment and explore the time-dependent association between the two scores. Methods: We included consecutive CHC patients treated with DAA and followed up with them for three years. Outcomes were changes from baseline (before DAA) in ASCVD and FIB-4 scores, measured at the end of treatment, 12-, 24-, and 36-months follow-up. Results: In total, 91 patients with CHC were finally included (median age: 66 years (IQR = 58−72 years); 43% females). Median follow-up was 2 years (1−3 years) and all patients reached SVR. The ASCVD score did not significantly change from baseline (Mean = 17.2%, 95% CI 14.1, 20.3), but the FIB-4 score significantly decreased at any time-point by an average of 0.8 (95% CI 0.78, 0.82, p < 0.001). Elevated FIB-4 scores at one (β = 1.16, p < 0.001) and three years (β = 2.52, p < 0.001) were associated with an increased ASCVD score. Clinically, two participants- with non-decreasing FIB-4 scores after treatment- had acute coronary syndrome at the end of treatment and one year follow-up, respectively. Conclusions: In our study, we found that FIB-4 and ASCVD scores exhibited a positive correlation irrespective of time-point after treatment. Larger studies are essential to further investigate the utility of FIB-4 scores in cardiovascular risk assessment.
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Affiliation(s)
- Mohammad Said Ramadan
- Department of Precision Medicine, University of Campania ‘L. Vanvitelli’ Napoli, 80138 Naples, Italy
| | - Filomena Boccia
- Department of Advanced Medical and Surgical Sciences, University of Campania ‘L. Vanvitelli’, 81031 Naples, Italy
| | - Simona Maria Moretto
- Department of Advanced Medical and Surgical Sciences, University of Campania ‘L. Vanvitelli’, 81031 Naples, Italy
| | - Fabrizio De Gregorio
- Department of Advanced Medical and Surgical Sciences, University of Campania ‘L. Vanvitelli’, 81031 Naples, Italy
| | - Massimo Gagliardi
- Department of Advanced Medical and Surgical Sciences, University of Campania ‘L. Vanvitelli’, 81031 Naples, Italy
| | - Domenico Iossa
- Unit of Infectious and Transplant Medicine, AORN Ospedali dei Colli-Monaldi Hospital, Piazzale E. Ruggieri, 80131 Naples, Italy
| | - Emanuele Durante-Mangoni
- Department of Precision Medicine, University of Campania ‘L. Vanvitelli’ Napoli, 80138 Naples, Italy
- Unit of Infectious and Transplant Medicine, AORN Ospedali dei Colli-Monaldi Hospital, Piazzale E. Ruggieri, 80131 Naples, Italy
| | - Rosa Zampino
- Department of Advanced Medical and Surgical Sciences, University of Campania ‘L. Vanvitelli’, 81031 Naples, Italy
- Unit of Infectious and Transplant Medicine, AORN Ospedali dei Colli-Monaldi Hospital, Piazzale E. Ruggieri, 80131 Naples, Italy
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Ghamar Talepoor A, Doroudchi M. Immunosenescence in atherosclerosis: A role for chronic viral infections. Front Immunol 2022; 13:945016. [PMID: 36059478 PMCID: PMC9428721 DOI: 10.3389/fimmu.2022.945016] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 07/26/2022] [Indexed: 01/10/2023] Open
Abstract
Immune system is a versatile and dynamic body organ which offers survival and endurance of human beings in their hostile living environment. However, similar to other cells, immune cells are hijacked by senescence. The ageing immune cells lose their beneficial functions but continue to produce inflammatory mediators which draw other immune and non-immune cells to the senescence loop. Immunosenescence has been shown to be associated with different pathological conditions and diseases, among which atherosclerosis has recently come to light. There are common drivers of both immunosenescence and atherosclerosis; e.g. inflammation, reactive oxygen species (ROS), chronic viral infections, genomic damage, oxidized-LDL, hypertension, cigarette smoke, hyperglycaemia, and mitochondrial failure. Chronic viral infections induce inflammaging, sustained cytokine signaling, ROS generation and DNA damage which are associated with atherogenesis. Accumulating evidence shows that several DNA and RNA viruses are stimulators of immunosenescence and atherosclerosis in an interrelated network. DNA viruses such as CMV, EBV and HBV upregulate p16, p21 and p53 senescence-associated molecules; induce inflammaging, metabolic reprogramming of infected cells, replicative senescence and telomere shortening. RNA viruses such as HCV and HIV induce ROS generation, DNA damage, induction of senescence-associated secretory phenotype (SASP), metabolic reprogramming of infected cells, G1 cell cycle arrest, telomere shortening, as well as epigenetic modifications of DNA and histones. The newly emerged SARS-CoV-2 virus is also a potent inducer of cytokine storm and SASP. The spike protein of SARS-CoV-2 promotes senescence phenotype in endothelial cells by augmenting p16, p21, senescence-associated β-galactosidase (SA-β-Gal) and adhesion molecules expression. The impact of SARS-CoV-2 mega-inflammation on atherogenesis, however, remains to be investigated. In this review we focus on the common processes in immunosenescence and atherogenesis caused by chronic viral infections and discuss the current knowledge on this topic.
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Kryukov EV, Cherkashin DV, Saluhov VV, Matjushenko KV, Sobolev AD, Shcherbina NN. Extrahepatic manifestations of chronic viral hepatitis C. BULLETIN OF THE RUSSIAN MILITARY MEDICAL ACADEMY 2022; 24:341-352. [DOI: 10.17816/brmma103982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Chronic viral diseases of the liver are frequently characterized by clinical signs of intrahepatic complications. Infection caused by the hepatitis C virus should be considered as a systemic disorder associated with the frequent development of various extrahepatic complications, such as cryoglobulinemia, glomerulopathy, lymphoproliferative diseases, seronegative arthritis, type 2 diabetes mellitus, lichen planus, and late cutaneous porphyria. Often, extrahepatic complications become the main features of the clinical disease picture, forcing patients to seek medical help from various specialists and delaying diagnosis. In some cases, the treatment of extrahepatic manifestations becomes an independent, complex task, surpassing the actual treatment of chronic hepatitis C. The relationship between hepatic and extrahepatic complications of viral hepatitis C is not linear; rather, extrahepatic manifestations often outstrip the development of liver damage. The effects of hepatitis C virus on the organs and systems of the body are caused by the direct action of the virus, pathogenetically induced by the development of steatosis/steatohepatitis, and by the disruption of system regulation of hepatokines and cytokines. Treatment of chronic hepatitis C virus infection should be comprehensive and should include antiviral therapy, treatment of metabolic-associated fatty liver disease and treatment of hepatic-related disorders. Antiviral therapy with preparations of direct antiviral action allows the prevention of not only liver complications but also of many extrahepatic complications of hepatitis C virus. Comorbid states significantly increase the natural progression of chronic hepatitis C infection and vice versa: the hepatitis C virus increases the clinical manifestations of co-pathology. In the age of direct antiviral drugs, it is possible to eliminate the hepatitis C virus, but in some cases, elimination alone does not arrest the progression of liver disease.
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Romano C, Tortorella O, Dalla Mora L, Di Stasio D, Sellitto A, Adinolfi LE, Marrone A. Prevalence and Outcome of Serum Autoantibodies in Chronic Hepatitis C Patients Undergoing Direct-Acting Antiviral Treatment. Front Immunol 2022; 13:882064. [PMID: 35479086 PMCID: PMC9038215 DOI: 10.3389/fimmu.2022.882064] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 03/22/2022] [Indexed: 12/26/2022] Open
Abstract
BackgroundChronic immune stimulation by hepatitis C virus (HCV) may cause occurrence of several autoantibodies in infected patients, with or without features of clinically overt autoimmune diseases. The recent introduction of direct-acting antivirals (DAAs) has dramatically changed the natural history of chronic HCV infection. The aim of this study was to assess the effects of DAA therapy on serum autoantibodies in chronic hepatitis C (CHC) patients.MethodsThe medical records of 113 CHC patients were reviewed to assess autoantibody behavior following DAA-directed HCV eradication. Statistical analysis was performed to assess correlations between DAA treatment and autoantibody titers, HCV genotypes, and viral loads.ResultsAnti-nuclear (ANA), anti-smooth muscle cell (ASMA) and anti-mitochondrial (AMA) antibody testing was available in 77 patients; 31 out of 77 patients (40%) had one or more serum autoantibodies prior to treatment. Measurement of autoantibody titers before and after HCV eradication was performed in 20 of 31 patients. DAA treatment significantly affected ANA and ASMA titers, leading to disappearance or reduction of autoantibody titers; conversely, AMA were not influenced by DAA treatment. No correlations were observed between autoantibody specificity and both HCV genotypes and viral loads at baseline. Likewise, serum autoantibody titers were independent of HCV genotypes.ConclusionsDAA-directed HCV clearance may interrupt chronic immune stimulation by removing the drive for autoantibody induction. The isolated persistence of autoantibodies in the small fraction of patients who did not show clearance following DAA treatment may require long-term vigilance.
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Affiliation(s)
- Ciro Romano
- Division of Internal Medicine, Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, Naples, Italy
- *Correspondence: Ciro Romano,
| | - Olga Tortorella
- Division of Internal Medicine, Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, Naples, Italy
| | - Liliana Dalla Mora
- Department of Precision Medicine, “Luigi Vanvitelli” University of Campania, Naples, Italy
| | - Dario Di Stasio
- Multidisciplinary Department of Medical and Dental Specialties, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Ausilia Sellitto
- Division of Internal Medicine, Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, Naples, Italy
| | - Luigi Elio Adinolfi
- Division of Internal Medicine, Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, Naples, Italy
| | - Aldo Marrone
- Division of Internal Medicine, Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, Naples, Italy
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22
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Freekh DA, Helmy MW, Said M, El-Khodary NM. The effect of direct acting antiviral agents on vascular endothelial function in Egyptian patients with chronic hepatitis C virus infection. Saudi Pharm J 2021; 29:1120-1128. [PMID: 34703365 PMCID: PMC8523355 DOI: 10.1016/j.jsps.2021.08.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 08/01/2021] [Indexed: 02/07/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection is correlated with cerebrovascular and cardiovascular disease (CVD). This study aimed to assess the effect of treatment with DAAs on vascular endothelial function in cirrhotic and non-cirrhotic HCV infected patients without any CVD risk factors. Fifty chronic HCV genotype 4 infected patients, without cardiovascular risks who have been listed to receive sofosbuvir/daclatasvir with ribavirin combination as triple therapy for 3 months were prospectively recruited. Endothelial dysfunction markers as soluble vascular cell adhesion molecule-1 (sVCAM-1) and Von willebrand factor (vWf) and inflammation marker (IL6) were estimated at baseline and 3 months post the end of therapy (SVR). All patients achieved SVR. VCAM1 level was significantly improved after HCV clearance with DAA in cirrhotic HCV patients (P = 0.002) compared to patients with mild liver fibrosis (P = 0.006). Levels of vWF also decreased significantly in cirrhosis and non-cirrhosis groups after SVR (P < 0.001 and P = 0.011, respectively). Systemic inflammatory marker (IL6) showed significant decrease in cirrhotic patients (P = 0.001). While, IL6 level did not change significantly in non-cirrhotic group (P = 0.061). Also at SVR, noninvasive liver fibrosis indices have been reduced significantly in the two groups (P < 0.001). HCV clearance by new DAA treatment improves the vascular endothelial dysfunction in Egyptian HCV infected patients with different levels of liver fibrosis and with no risk factors for endothelial dysfunction or CVD.
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Affiliation(s)
- Dalia A Freekh
- Clinical Pharmacy & Pharmacy Practice Department, Faculty of Pharmacy, Damanhour University, Damanhour City, Egypt
| | - Maged W Helmy
- Professor of Pharmacology & Toxicology, Pharmacology & Toxicology Department, Faculty of Pharmacy, Damanhour University, Damanhour City, Egypt
| | - Mohamed Said
- Professor of Endemic Medicine & Hepatology, Endemic Medicine & Hepatology Department, Cairo University, Cairo City, Egypt
| | - Noha M El-Khodary
- Lecturer of Clinical Pharmacy, Clinical Pharmacy & Pharmacy Practice Department, Faculty of Pharmacy, Damanhour University, Damanhour City, Egypt
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Onohuean H, Al-kuraishy HM, Al-Gareeb AI, Qusti S, Alshammari EM, Batiha GES. Covid-19 and development of heart failure: mystery and truth. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2021; 394:2013-2021. [PMID: 34480616 PMCID: PMC8417660 DOI: 10.1007/s00210-021-02147-6] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 08/26/2021] [Indexed: 02/07/2023]
Abstract
Coronavirus disease 2019 (Covid-19) is a novel worldwide pandemic caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). During Covid-19 pandemic, socioeconomic deprivation, social isolation, and reduced physical activities may induce heart failure (HF), destabilization, and cause more complications. HF appears as a potential hazard due to SARS-CoV-2 infection, chiefly in elderly patients with underlying comorbidities. In reality, the expression of cardiac ACE2 is implicated as a target point for SARS-CoV-2-induced acute cardiac injury. In SARS-CoV-2 infection, like other febrile illnesses, high blood viscosity, exaggerated pro-inflammatory response, multisystem inflammatory syndrome, and endothelial dysfunction-induced coagulation disorders may increase risk of HF development. Hypoxic respiratory failure, as in pulmonary edema, severe acute lung injury (ALI), and acute respiratory distress syndrome (ARDS) may affect heart hemodynamic stability due to the development of pulmonary hypertension. Indeed, Covid-19-induced HF could be through the development of cytokine storm, characterized by high proliferation pro-inflammatory cytokines. In cytokine storm-mediated cardiac dysfunction, there is a positive correlation between levels of pro-inflammatory cytokine and myocarditis-induced acute cardiac injury biomarkers. Therefore, Covid-19-induced HF is more complex and related from a molecular background in releasing pro-inflammatory cytokines to the neuro-metabolic derangements that together affect cardiomyocyte functions and development of HF. Anti-heart failure medications, mainly digoxin and carvedilol, have potent anti-SARS-CoV-2 and anti-inflammatory properties that may mitigate Covid-19 severity and development of HF. In conclusion, SARS-CoV-2 infection may lead to the development of HF due to direct acute cardiac injury or through the development of cytokine storms, which depress cardiomyocyte function and cardiac contractility. Anti-heart failure drugs, mainly digoxin and carvedilol, may attenuate severity of HF by reducing the infectivity of SARS-CoV-2 and prevent the development of cytokine storms in severely affected Covid-19 patients.
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Affiliation(s)
- Hope Onohuean
- Department of Pharmacology and Toxicology, Biopharmaceutics Unit, School of Pharmacy, Kampala International University, Western-Campus, Kampala, Uganda
| | - Hayder M. Al-kuraishy
- Department of Clinical Pharmacology and Medicine, College of Medicine, ALmustansiriyia University, Baghdad, Iraq
| | - Ali I. Al-Gareeb
- Department of Clinical Pharmacology and Medicine, College of Medicine, ALmustansiriyia University, Baghdad, Iraq
| | - Safaa Qusti
- Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Eida M. Alshammari
- Department of Chemistry, College of Sciences, University of Ha’il, Ha’il, Saudi Arabia
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, AlBeheira, 22511 Egypt
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Sasso FC, Pafundi PC, Caturano A, Galiero R, Vetrano E, Nevola R, Petta S, Fracanzani AL, Coppola C, Di Marco V, Solano A, Lombardi R, Giordano M, Craxi A, Perrella A, Sardu C, Marfella R, Salvatore T, Adinolfi LE, Rinaldi L. Impact of direct acting antivirals (DAAs) on cardiovascular events in HCV cohort with pre-diabetes. Nutr Metab Cardiovasc Dis 2021; 31:2345-2353. [PMID: 34053830 DOI: 10.1016/j.numecd.2021.04.016] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 04/19/2021] [Accepted: 04/20/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Beyond type 2 diabetes, even a condition of prediabetes is associated with an increased cardiovascular (CV) risk, and HCV infection coexistence represents an exacerbating factor. CV prognosis improvement in prediabetes represents a challenge, due to the increasing prevalence of this metabolic condition worldwide. Hence, we aimed to prospectively assess how direct acting antivirals (DAAs) could affect major cardiovascular events (MACE) in a prediabetic HCV positive cohort. METHODS AND RESULTS In this prospective multicenter study, we enrolled HCV patients with overt prediabetes. We compared a subgroup of patients treated with DAAs with untreated prediabetic controls. We recorded all CV events occurred during an overall median follow-up of 24 months (IQR 19-34). 770 HCV positive prediabetic patients were enrolled, 398 untreated controls and 372 DAAs treated patients. Overall, the CV events annual incidence was much higher among prediabetic treated patients (1.77 vs. 0.62, p < 0.001), and HCV clearance demonstrated to significantly reduce CV events (RR: 0.411, 95%CI 0.148-1.143; p < 0.001), with an estimated NNT for one additional patient to benefit of 52.1. Moreover, an independent association between a lower rate of CV events and HCV clearance after DAAs was observed (OR 4.67; 95%CI 0.44-53.95; p = 0.016). CONCLUSIONS HCV eradication by DAAs allows a significant reduction of MACEs in the prediabetic population, and therefore represents a primary objective, regardless of the severity of liver disease and CV risk factors.
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Affiliation(s)
- Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138, Naples, Italy.
| | - Pia Clara Pafundi
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138, Naples, Italy
| | - Alfredo Caturano
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138, Naples, Italy
| | - Raffaele Galiero
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138, Naples, Italy
| | - Erica Vetrano
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138, Naples, Italy
| | - Riccardo Nevola
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138, Naples, Italy
| | - Salvatore Petta
- Division of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy
| | - Anna Ludovica Fracanzani
- Department of Pathophysiology and Transplantation, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, University of Milan, Italy
| | - Carmine Coppola
- Unit of Internal Medicine and Hepatolology, Gragnano Hospital, ASL Napoli 3 Sud, Gragnano, Napoli, Italy
| | - Vito Di Marco
- Division of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy
| | - Antonio Solano
- Unit of Hepatology, Pellegrini Hospital, ASL Napoli 1 Centro, Naples, Italy
| | - Rosa Lombardi
- Department of Pathophysiology and Transplantation, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, University of Milan, Italy
| | - Mauro Giordano
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138, Naples, Italy
| | - Antonio Craxi
- Division of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy
| | | | - Celestino Sardu
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138, Naples, Italy
| | - Raffaele Marfella
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138, Naples, Italy
| | - Teresa Salvatore
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via De Crecchio 7, 80138, Naples, Italy
| | - Luigi Elio Adinolfi
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138, Naples, Italy
| | - Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138, Naples, Italy.
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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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26
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Fabrizi F, Cerutti R, Donato FM, Messa P. HBV infection is a risk factor for chronic kidney disease: Systematic review and meta-analysis. Rev Clin Esp 2021; 221:600-611. [PMID: 34183297 DOI: 10.1016/j.rceng.2019.10.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2019] [Accepted: 10/06/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND The activity of hepatitis B virus (HBV) as a risk factor for the incidence and progression of chronic kidney disease (CKD) has not been clarified. AIM We evaluated the impact of infection with HBV on the risk of CKD in the general population. MATERIAL AND METHODS We carried out a systematic review of the published medical literature to assess whether a relationship between hepatitis B infection and an increased risk of CKD in the adult general population occurs. We adopted the random effects model of DerSimonian and Laird to provide a summary estimate of the risk of chronic kidney disease (defined by lowered glomerular filtration rate and/or detectable proteinuria) with HBV infection across the published studies. Meta-regression and stratified analyses were also performed. RESULTS We retrieved 33 studies (n = 7,849,849 patients) published in 26 different articles, and separate meta-analyses were performed according to the outcome. Pooling results from cohort studies (11 studies, n = 1,056,645 patients) demonstrated a relationship between positive HBV serologic status and increased incidence of CKD, the summary estimate for adjusted HR with HBV across the surveys, 1.40 (95% CI, 1.16-1.69) (P < .001). Between-study heterogeneity was noted (Q value, 49.5, P < .0001). No relationship between HBV and prevalence of CKD was noted in the subset of cross-sectional studies (10 studies; n = 3,222,545 patients), adjusted OR, 1.04 (95% IC 0.90-1.218; P = .5). Meta-regression analysis reported a relationship between positive HBsAg status and incidence of CKD in the general population (P < .015). CONCLUSIONS It appears that exposure to HBV infection seems to be associated with an increased risk of developing CKD in the adult general population. Studies aimed to understand the mechanisms responsible of such association are under way.
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Affiliation(s)
- F Fabrizi
- Division of Nephrology, Dialysis and Renal Transplantation, Maggiore Policlinico Hospital and Cà Granda IRCCS Foundation, Milano, Italy.
| | - R Cerutti
- Division of Nephrology, Dialysis and Renal Transplantation, Maggiore Policlinico Hospital and Cà Granda IRCCS Foundation, Milano, Italy
| | - F M Donato
- Division of Gastroenterology and Hepatology, Maggiore Policlinico Hospital and Ca' Granda IRCCS Foundation, Milano, Italy
| | - P Messa
- Division of Nephrology, Dialysis and Renal Transplantation, Maggiore Policlinico Hospital and Cà Granda IRCCS Foundation, Milano, Italy; University School of Medicine, Milano, Italy
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27
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Liver-Related and Cardiovascular Outcome of Patients Transplanted for Nonalcoholic Fatty Liver Disease: A European Single-Center Study. Transplant Proc 2021; 53:1674-1681. [PMID: 34016462 DOI: 10.1016/j.transproceed.2021.02.025] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 01/18/2021] [Accepted: 02/25/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND The increasing rate of liver transplantation (LT) for nonalcoholic fatty liver disease (NAFLD) raises concerns on cardiovascular morbidity and mortality after LT in these patients. METHODS We collected variables regarding the presence of metabolic risk factors, NAFLD recurrence, cardiovascular morbidity, and overall survival at time of listing and after LT of 112 patients with NAFLD and a control group of 120 patients with hepatitis C (HCV). RESULTS Metabolic syndrome and cardiovascular morbidity component rates (24.1% vs 12.5%) at the time of LT listing were higher in patients with NAFLD compared with patients with HCV (for all, P < .0390). Median follow-up after LT was 5.6 years in patients with NAFLD vs 13.5 years in patients with HCV (P = .0009). There was no difference in 6-weeks postoperative mortality (1.7% vs 2.5%) (P =1.0000). Metabolic syndrome components after LT were more frequent in patients with NAFLD than in patients with HCV (for all, P < .0008). The incidence of NAFLD 5 years after LT was higher in patients transplanted for NAFLD compared with HCV (43.5% vs 4.2%) (P < .0001). Patients with recurrent NAFLD more often had myocardial infarction compared with those without recurrence (8.3% vs 0%) (P = .0313). Five years after LT, cardiovascular morbidity was more frequent in the NAFLD group than in the HCV group (12.8% vs 9.3%) (P = .0256), whereas no difference in overall survival was observed. CONCLUSION LT for NAFLD is associated with satisfactory 5-year outcomes; however, our data underscore the need for close monitoring and aggressive management of cardiovascular risk factors in these patients.
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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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Shengir M, Elgara M, Sebastiani G. Metabolic and cardiovascular complications after virological cure in hepatitis C: What awaits beyond. World J Gastroenterol 2021; 27:1959-1972. [PMID: 34007133 PMCID: PMC8108037 DOI: 10.3748/wjg.v27.i17.1959] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 03/06/2021] [Accepted: 04/12/2021] [Indexed: 02/06/2023] Open
Abstract
The association between chronic hepatitis C (CHC) infection and extrahepatic manifestations (EHMs), particularly cardiometabolic diseases, has been extensively examined. However, there has still been insufficient evaluation for these EHMs after virological cure. Several multidirectional mechanisms have been proposed explaining the ability of hepatitis C virus (HCV) developing EHMs, cardiometabolic ones, as well as the effect of antiviral therapy to resolve these EHMs. Data on these manifestations after achieving sustained virologic response (SVR) are still conflicting. However, current evidence suggests that reversal of hepatic steatosis and its coexistent hypocholesterolemia after successful viral eradication led to unfavorable lipid profile, which increases cardiovascular disease (CVD) risk. Additionally, most observations showed that metabolic alterations, such as insulin resistance and diabetes mellitus (DM), undergo some degree of reduction after viral clearance. These changes seem HCV-genotype dependent. Interferon-based antiviral therapy and direct acting antiviral drugs were shown to minimize incidence of DM. Large epidemiological studies that investigated the effect of SVR on CVD showed great discrepancies in terms of results, with predominant findings indicating that CVD events decreased in patients with SVR compared to non-responders or untreated ones. In this review, we present a summary of the current knowledge regarding extrahepatic sequelae of CHC following SVR, which may have an impact on healthcare providers’ clinical practice.
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Affiliation(s)
- Mohamed Shengir
- Department of Medicine, McGill University, Montreal, Quebec H3A0G4, Canada
| | - Mohamed Elgara
- Department of Internal Medicine, Hamad Medical Corporation, Doha 3050, Qatar
| | - Giada Sebastiani
- Department of Medicine, McGill University Health Center, Montreal, Quebec H4A3J1, Canada
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Effect of Direct Antiviral Agents on Atherosclerosis in Patients with Chronic Hepatitis C. Arch Med Res 2021; 52:764-771. [PMID: 33972118 DOI: 10.1016/j.arcmed.2021.04.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 03/27/2021] [Accepted: 04/15/2021] [Indexed: 12/18/2022]
Abstract
BACKGROUND Chronic hepatitis C is an independent risk factor for atherosclerosis and is associated with cardiovascular events. Mechanisms include inflammatory cytokines, endothelial dysfunction, and increased oxidative stress. AIM OF THE STUDY The objective was to evaluate the response of carotid atherosclerosis to treatment with direct-antiviral agents. METHODS We developed a prospective cohort study that included patients with chronic hepatitis C treated with direct-acting antiviral agents (DAAs), without cardiovascular disease, diabetes mellitus, significative chronic kidney disease or coinfections. Clinical characteristics, laboratory values and carotid ultrasound to measure carotid intima-media thickness (CIMT) and look for established atherosclerosis were performed at baseline and 3 months after completing treatment with DAAs. RESULTS A total of 24 patients were included. The mean age was 60 years and 79% were women. The prevalence of smoking was 41.7%, obesity 25% and hypertension 20.8%. Age, arterial hypertension, genotype, AST, glomerular filtration rate and cirrhosis were significantly associated with established carotid atherosclerosis. After treatment with DAAs, an overall significant reduction of C-reactive protein (CRP) levels was found (p = 0.004). A trend towards reduction of significant CIMT (>0.9 mm) (20.8 vs. 8.3%, RR 1.18, IC 95% 0.75-1.86, p = 0.29) and a statistically significant resolution of atherosclerotic plaque (45.8 vs. 41.7% RR 0.09, IC 95% 0.01-0.63, p = 0.001) was found. CONCLUSIONS Treatment of chronic hepatitis C with DAAs decrease carotid thickening, atheromatous plaques, and inflammatory markers like CRP. More studies are needed to confirm this finding and its impact on long-term cardiovascular outcomes.
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31
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Tassi A, Gitto S, Piras C, Cursaro C, Alicandro T, Margotti M, Rivi M, Andreone P. Cognitive, neurological and psychiatric disorders occurring in Hepatitis C Virus infection. Minerva Med 2021; 112:238-245. [PMID: 33576202 DOI: 10.23736/s0026-4806.21.07388-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Chronic Hepatitis C is associated with many extrahepatic manifestations. Central nervous system is frequently involved, but the pathophysiological mechanisms are not fully understood. Local and systemic inflammation, ischemia, immune-mediated phenomena have been described in this context. Clinical manifestations include cognitive alterations, stroke, depression and demyelinating phenomena. It is unclear if cognitive deficits can be improved or resolved with viral eradication and to understand this, could have important therapeutical implications.
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Affiliation(s)
- Andrea Tassi
- Division of Internal Medicine, Department of Medical and Surgical Sciences, Maternal-Infantile and Adult, University of Modena and Reggio Emilia, Modena, Italy
| | - Stefano Gitto
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Chiara Piras
- Graduating School of Medicine and Surgery, University of Modena and Reggio Emilia, Modena, Italy
| | - Carmela Cursaro
- Division of Internal Medicine, Department of Medical and Surgical Sciences, Maternal-Infantile and Adult, University of Modena and Reggio Emilia, Modena, Italy
| | - Tatiana Alicandro
- Division of Internal Medicine, Department of Medical and Surgical Sciences, Maternal-Infantile and Adult, University of Modena and Reggio Emilia, Modena, Italy
- Postgraduate School of Allergy and Clinical Immunology, University of Modena and Reggio Emilia, Modena, Italy
| | - Marzia Margotti
- Division of Internal Medicine, Department of Medical and Surgical Sciences, Maternal-Infantile and Adult, University of Modena and Reggio Emilia, Modena, Italy
| | - Marco Rivi
- Division of Internal Medicine, Department of Medical and Surgical Sciences, Maternal-Infantile and Adult, University of Modena and Reggio Emilia, Modena, Italy
- Postgraduate School of Allergy and Clinical Immunology, University of Modena and Reggio Emilia, Modena, Italy
| | - Pietro Andreone
- Division of Internal Medicine, Department of Medical and Surgical Sciences, Maternal-Infantile and Adult, University of Modena and Reggio Emilia, Modena, Italy -
- Postgraduate School of Allergy and Clinical Immunology, University of Modena and Reggio Emilia, Modena, Italy
- Unit of Internal and Metabolic Medicine, Civil Hospital of Baggiovara, University of Modena and Reggio Emilia, Baggiovara, Modena, Italy
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32
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Su X, Zhao X, Deng JL, Li SN, Du X, Dong JZ, Ma CS. Antiviral treatment for hepatitis C is associated with a reduced risk of atherosclerotic cardiovascular outcomes: A systematic review and meta-analysis. J Viral Hepat 2021; 28:664-671. [PMID: 33452699 DOI: 10.1111/jvh.13469] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 01/04/2021] [Indexed: 12/13/2022]
Abstract
Hepatitis C virus infection (HCV) may be associated with a greater risk of cardiovascular disease (CVD), and the evidence for whether antiviral therapy for HCV could reduce the risk of CVD events is inconsistent. The aim of this meta-analysis was to investigate the association between anti-HCV treatment and the risk of CVD. We searched PubMed, EMBASE and Cochrane Library databases from inception to 20 August 2020. The pooled hazard ratio (HR) with 95% confidence interval (CI) of the risk of CVD events [any CVD, coronary artery disease (CAD) and stroke] was calculated using the random-effects model. A total of eleven studies, including 309,470 subjects, were enrolled in this meta-analysis. Among those, four studies reported on any CVD between anti-HCV-treated and anti-HCV-untreated patients, five studies reported on CAD, and five studies reported on stroke. Also, five studies reported on any CVD between patients with sustained virological response (SVR) and without SVR. Overall, antiviral therapy for HCV was associated with a reduced risk of any CVD (HR = 0.64, 95% CI: 0.50-0.83), CAD (HR = 0.73, 95% CI: 0.55-0.96) and stroke (HR = 0.74, 95% CI: 0.64-0.86). Besides, we found that SVR was associated with a significant decrease in any CVD compared with non-SVR (HR = 0.74, 95% CI: 0.60-0.92). In conclusion, this meta-analysis demonstrated that antiviral therapy for HCV was associated with a reduced risk of CVD events. In addition, the risk of CVD events was lower in individuals with SVR compared with those without SVR.
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Affiliation(s)
- Xin Su
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Chaoyang District, China
| | - Xin Zhao
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Chaoyang District, China
| | - Jia-Long Deng
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Chaoyang District, China
| | - Song-Nan Li
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Chaoyang District, China
| | - Xin Du
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Chaoyang District, China
| | - Jian-Zeng Dong
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Chaoyang District, China
| | - Chang-Sheng Ma
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Chaoyang District, China
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33
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Iossa D, Vitrone M, Gagliardi M, Falco E, Ragone E, Zampino R, Durante-Mangoni E. Anthropometric parameters and liver histology influence lipid metabolic changes in HCV chronic hepatitis on direct-acting antiviral treatment. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:35. [PMID: 33553328 PMCID: PMC7859777 DOI: 10.21037/atm-20-669] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Background Hepatitis C virus (HCV) infection affects lipid metabolism. We investigated the impact of direct-acting antiviral (DAA) treatment on lipid metabolism in chronic hepatitis C (CHC), with a focus on the effects of anthropometric parameters and liver histology. We also analyzed the dynamics of metabolic indexes used to estimate cardiovascular risk. Methods In 49 patients with CHC treated with DAAs, lipid metabolic changes, anthropometric parameters, liver histology and cardiovascular risk indexes, including triglyceride to HDL ratio (Tr/HDL), fatty liver index (FLI) and visceral adiposity index (VAI) were evaluated at baseline (BL), end of treatment (EOT) and 12 [sustained virological response (SVR) 12] and 24 (SVR24) weeks after EOT. Results SVR occurred in 96% of cases. Total and LDL cholesterol and ApoB levels increased significantly between BL and EOT (P<0.001, <0.001 and 0.05, respectively) and remained stable thereafter. Total and LDL cholesterol significantly increased only in patients with higher BL waist circumference (P<0.01 and 0.009), fibrosis (P=0.002 and 0.005) and steatosis (P=0.043 and 0.033, respectively). HDL cholesterol significantly rose at SVR24. However, cardiovascular risk indexes (Tr/HDL ratio, FLI and VAI) did not significantly change during DAA treatment and follow up. Conclusions Patients with HCV eradication after DAA treatment develop a pro-atherogenic lipid pattern, which varies according to anthropometric parameters and liver histology. However, no increase of cardiovascular risk indexes occurs in the short-term. Total and LDL cholesterol should be monitored long-term in CHC patients cured from infection.
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Affiliation(s)
- Domenico Iossa
- Internal Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | - Martina Vitrone
- Internal Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | - Massimo Gagliardi
- Internal Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | - Erasmo Falco
- Units of Infectious & Transplant Medicine AORN dei Colli, Monaldi Hospital, Naples, Italy
| | - Enrico Ragone
- Units of Infectious & Transplant Medicine AORN dei Colli, Monaldi Hospital, Naples, Italy
| | - Rosa Zampino
- Internal Medicine, University of Campania "L. Vanvitelli", Naples, Italy.,Units of Infectious & Transplant Medicine AORN dei Colli, Monaldi Hospital, Naples, Italy
| | - Emanuele Durante-Mangoni
- Internal Medicine, University of Campania "L. Vanvitelli", Naples, Italy.,Units of Infectious & Transplant Medicine AORN dei Colli, Monaldi Hospital, Naples, Italy
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34
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Scudiero F, Valenti R, Marcucci R, Sanna GD, Gori AM, Migliorini A, Vitale R, Giusti B, De Vito E, Corda G, Paniccia R, Zirolia D, Canonico ME, Parodi G. Platelet Reactivity in Hepatitis C Virus-Infected Patients on Dual Antiplatelet Therapy for Acute Coronary Syndrome. J Am Heart Assoc 2020; 9:e016441. [PMID: 32885738 PMCID: PMC7726996 DOI: 10.1161/jaha.120.016441] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Background Coronary artery disease (CAD) has been recognized as a serious and potentially life‐threatening complication of Hepatitis C Virus (HCV) infection. High on‐treatment platelet reactivity has been associated with high risk of ischemic events in patients with CAD, but data regarding the association with HCV infection are still lacking. This post hoc analysis aims to assess high on‐treatment platelet reactivity, severity of CAD, and long‐term outcomes of patients with acute coronary syndrome (ACS) who were infected with HCV. Methods and Results Patients with ACS who were infected with HCV (n=47) were matched to patients with ACS and without HCV (n=137) for age, sex, diabetes mellitus, hypertension, and renal function. HCV‐infected patients with ACS had higher levels of platelet reactivity (ADP10–light transmittance aggregometry, 56±18% versus 44±22% [P=0.002]; arachidonic acid–light transmittance aggregometry, 25±21% versus 16±15% [P=0.011]) and higher rates of high on‐treatment platelet reactivity on clopidogrel and aspirin compared with patients without HCV. Moreover, HCV‐infected patients with ACS had higher rates of multivessel disease (53% versus 30%; P=0.004) and 3‐vessel disease (32% versus 7%; P<0.001) compared with patients without HCV. At long‐term follow‐up, estimated rates of major adverse cardiovascular events (cardiac death, nonfatal myocardial infarction, and ischemia‐driven revascularization) were 57% versus 34% (P=0.005) in HCV‐ and non–HCV‐infected patients with ACS, respectively. In addition, thrombolysis In Myocardial Infarction (TIMI) major bleeding rates were higher in HCV‐infected patients (11% versus 3%; P=0.043) compared with noninfected patients. Multivariable analysis demonstrated that HCV infection was an independent predictor of high on‐treatment platelet reactivity, severity of CAD, and long‐term outcome. Conclusions In this hypothesis‐generating study, patients with ACS and HCV infection showed increased on‐treatment platelet reactivity, more severe CAD, and worse prognosis compared with patients without HCV.
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Affiliation(s)
- Fernando Scudiero
- Department of Clinical and Experimental Medicine University of Florence Italy.,Cardiology Unit ASST Bergamo est Bolognini Hospital Seriate Italy
| | - Renato Valenti
- Department of Clinical and Experimental Medicine University of Florence Italy
| | - Rossella Marcucci
- Department of Clinical and Experimental Medicine University of Florence Italy
| | | | - Anna Maria Gori
- Department of Clinical and Experimental Medicine University of Florence Italy
| | - Angela Migliorini
- Department of Clinical and Experimental Medicine University of Florence Italy
| | - Raffaele Vitale
- Department of Clinical and Experimental Medicine University of Florence Italy
| | - Betti Giusti
- Department of Clinical and Experimental Medicine University of Florence Italy
| | - Elena De Vito
- Department of Clinical and Experimental Medicine University of Florence Italy
| | - Giulia Corda
- Cardiology Clinic Sassari University Hospital Sassari Italy.,Department of Medical, Surgical and Experimental Sciences Sassari University Sassari Italy
| | - Rita Paniccia
- Department of Clinical and Experimental Medicine University of Florence Italy
| | - Davide Zirolia
- Cardiology Clinic Sassari University Hospital Sassari Italy.,Department of Medical, Surgical and Experimental Sciences Sassari University Sassari Italy
| | - Mario E Canonico
- Cardiology Clinic Sassari University Hospital Sassari Italy.,Department of Medical, Surgical and Experimental Sciences Sassari University Sassari Italy
| | - Guido Parodi
- Cardiology Clinic Sassari University Hospital Sassari Italy.,Department of Medical, Surgical and Experimental Sciences Sassari University Sassari Italy
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Reyentovich A, Gidea CG, Smith D, Lonze B, Kon Z, Fargnoli A, Pavone J, Rao S, Saraon T, Lewis T, Qian Y, Jacobson I, Moazami N. Outcomes of the Treatment with Glecaprevir/Pibrentasvir following heart transplantation utilizing hepatitis C viremic donors. Clin Transplant 2020; 34:e13989. [DOI: 10.1111/ctr.13989] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 05/14/2020] [Accepted: 05/17/2020] [Indexed: 12/13/2022]
Affiliation(s)
- Alex Reyentovich
- Division of Cardiology Department of Medicine NYU Langone Medical Center New York NY USA
| | - Claudia G. Gidea
- Division of Cardiology Department of Medicine NYU Langone Medical Center New York NY USA
| | - Deane Smith
- Department of Cardiothoracic Surgery NYU Langone Medical Center New York NY USA
| | - Bonnie Lonze
- Department of Renal Transplant Surgery NYU Langone Medical Center New York NY USA
| | - Zachary Kon
- Department of Cardiothoracic Surgery NYU Langone Medical Center New York NY USA
| | - Anthony Fargnoli
- Department of Cardiothoracic Surgery NYU Langone Medical Center New York NY USA
| | - Jennifer Pavone
- Division of Cardiology Department of Medicine NYU Langone Medical Center New York NY USA
| | - Shaline Rao
- Division of Cardiology Department of Medicine NYU Langone Medical Center New York NY USA
| | - Tajinderpal Saraon
- Division of Cardiology Department of Medicine NYU Langone Medical Center New York NY USA
| | - Tyler Lewis
- Department of Pharmacy NYU Langone Medical Center New York NY USA
| | - Yingzhi Qian
- Department of Population Health Biostatistics Division NYU Langone Medical Center New York NY USA
| | - Ira Jacobson
- Department of Gastroenterology NYU Langone Medical Center New York NY USA
| | - Nader Moazami
- Department of Cardiothoracic Surgery NYU Langone Medical Center New York NY USA
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36
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Durazzo TC, Nguyen LC, Meyerhoff DJ. Medical Conditions Linked to Atherosclerosis Are Associated With Magnified Cortical Thinning in Individuals With Alcohol Use Disorders. Alcohol Alcohol 2020; 55:382-390. [PMID: 32445335 PMCID: PMC7307314 DOI: 10.1093/alcalc/agaa034] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Revised: 03/19/2020] [Accepted: 04/09/2020] [Indexed: 01/21/2023] Open
Abstract
AIMS Magnetic resonance imaging (MRI) studies report widespread cortical thinning in individuals with alcohol use disorder (AUD), but did not consider potential effects of pro-atherogenic conditions such as hypertension, type 2 diabetes mellitus, hepatitis C seropositivity and hyperlipidemia on cortical thickness. The conditions are associated with regional cortical thinning in those without AUD. We predicted that individuals with concurrent AUD and pro-atherogenic conditions demonstrate the greatest regional cortical thinning in areas most vulnerable to decreased perfusion. METHODS Treatment-seeking individuals with AUD (n = 126) and healthy controls (CON; n = 49) completed a 1.5 T MRI study. Regional cortical thickness was quantitated via FreeSurfer. Individuals with AUD and pro-atherogenic conditions (Atherogenic+), AUD without pro-atherogenic conditions (Atherogenic-) and CON were compared on regional cortical thickness. RESULTS Individuals with AUD showed significant bilateral cortical thinning compared to CON, but Atherogenic+ demonstrated the most widespread and greatest magnitude of regional thinning, while Atherogenic- had reduced thickness primarily in anterior frontal and posterior parietal lobes. Atherogenic+ also showed a thinner cortex than Atherogenic- in lateral orbitofrontal and dorso/dorsolateral frontal cortex, mesial and lateral temporal and inferior parietal regions. CONCLUSIONS Our results demonstrate significant bilateral cortical thinning in individuals with AUD relative to CON, but the distribution and magnitude were influenced by comorbid pro-atherogenic conditions. The magnitude of cortical thinning in Atherogenic+ strongly corresponded to cortical watershed areas susceptible to decreased perfusion, which may result in morphometric abnormalities. The findings indicate that pro-atherogenic conditions may contribute to cortical thinning in those seeking treatment for AUD.
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Affiliation(s)
- Timothy C Durazzo
- Mental Illness Research and Education Clinical Centers, VA Palo Alto Health Care System, Palo Alto, CA, USA
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Linh-Chi Nguyen
- Mental Illness Research and Education Clinical Centers, VA Palo Alto Health Care System, Palo Alto, CA, USA
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Dieter J Meyerhoff
- Center for Imaging of Neurodegenerative Diseases (CIND), San Francisco VA Medical Center, San Francisco, CA, USA
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
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37
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Mohanty A, Salameh S, Butt AA. Impact of Direct Acting Antiviral Agent Therapy upon Extrahepatic Manifestations of Hepatitis C Virus Infection. Curr HIV/AIDS Rep 2020; 16:389-394. [PMID: 31482299 DOI: 10.1007/s11904-019-00466-1] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
PURPOSE OF REVIEW Direct acting antiviral agents (DAAs) have emerged as simple, short, safe, and effective treatments for chronic hepatitis C (CHC) infection. CHC is a systemic disease with frequent and multiple extrahepatic manifestations. The beneficial effects of DAA treatment regimens extend beyond improvement in liver-related outcomes to amelioration of extra hepatic manifestations and are likely to have economic implications. The purpose of this review is to evaluate the effect of DAAs on extra hepatic manifestations of CHC virus infection. RECENT FINDINGS Recent studies indicate that DAAs are associated with reduction in all-cause mortality, even in patients without significant hepatic fibrosis. They are also associated with reduction in incident cardiovascular disease and diabetes. DAAs are the mainstay of treatment in HCV-associated cryoglobulinemia and lymphoma. Successful HCV therapy with DAAs also improves patient-related outcomes such as health-related quality of life. DAAs improve extrahepatic manifestations of CHC virus infection. Future studies are needed to evaluate the long-term durability of treatment response and for accounting amelioration of extrahepatic manifestations into the cost effectiveness of DAA regimens.
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Affiliation(s)
- Arpan Mohanty
- Boston University School of Medicine, Boston, MA, USA
| | | | - Adeel A Butt
- Hamad Medical Corporation, Doha, Qatar. .,VA Pittsburgh Healthcare System, Pittsburgh, PA, USA. .,Weill Cornell Medical College, New York, NY, USA. .,Weill Cornell Medical College, Doha, Qatar.
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38
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Zhang T, Jiang Y, Zhang S, Tie T, Cheng Y, Su X, Man Z, Hou J, Sun L, Tian M, Zhang Y, Li J, Ma Y. The association between homocysteine and ischemic stroke subtypes in Chinese: A meta-analysis. Medicine (Baltimore) 2020; 99:e19467. [PMID: 32195946 PMCID: PMC7220264 DOI: 10.1097/md.0000000000019467] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND The findings on the association between elevated plasma homocysteine levels and the risk of the trial of org 10172 in acute stroke treatment (TOAST) of ischemic stroke have been inconsistent in Chinese. So far, there is no meta-analysis about the association between Hcy and the TOAST subtypes of ischemic stroke in Chinese. This study; therefore, aimed to evaluate whether elevated homocysteine levels are associated with the TOAST subtypes of ischemic stroke using a meta-analysis. MATERIALS AND METHODS A systematic search of electronic databases were conducted for studies reporting homocysteine levels in ischemic stroke and the TOAST of ischemic stroke to April 18, 2018. The data were extracted after the application of inclusion and exclusion criteria. All the data were analyzed using Stata software version 9.0 (Stata Corp LP, College Station, TX). The standardized mean difference (SMD) and 95% confidence interval (CI) were used to compare continuous variables. RESULTS Thirteen studies comprising 3114 participants (2243 patients and 871controls) met the eligibility criteria and were included in the meta-analysis. The meta-analysis revealed that the ischemic stroke group had significantly higher levels of homocysteine than controls (SMD = 1.15, 95% CI = 0.85-1.45, P < .05). The subgroup analyses suggested that the groups of patients with large-artery atherosclerosis, small-vessel occlusion, cardioembolism, stroke of other determined etiology and stroke of undetermined etiology had significantly higher levels of homocysteine compared to those in the control group (large-artery atherosclerosis: SMD = 2.12, 95% CI = 1.40-2.84, P < .05; small-vessel occlusion: SMD = 1.10, 95% CI = 0.72-1.48, P < .05; CE: SMD = 1.17, 95% CI = 0.64-1.71, P < .05; stroke of other determined etiology: SMD = 0.88, 95% CI = 0.53-1.24, P < .05; stroke of undetermined etiology: SMD = 1.50, 95% CI = 0.66-2.33, P < .05, respectively). CONCLUSION This meta-analysis found that ischemic stroke patients and the TOAST of ischemic stroke patients in Chinese had significantly higher homocysteine levels than the controls, suggesting that serum homocysteine levels may be a risk factor for ischemic stroke and the TOAST subtypes of ischemic stroke in Chinese.
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Affiliation(s)
- Tao Zhang
- Qinghai University Affiliated Hospital, Xining, Qinghai Province
| | - Yuan Jiang
- Qinghai University Affiliated Hospital, Xining, Qinghai Province
| | - Shuhua Zhang
- Tengzhou Central People's Hospital, Zaozhuang, Shandong province, China
| | - Tingting Tie
- Qinghai University Affiliated Hospital, Xining, Qinghai Province
| | - Yan Cheng
- Qinghai University Affiliated Hospital, Xining, Qinghai Province
| | - Xiaoming Su
- Qinghai University Affiliated Hospital, Xining, Qinghai Province
| | - Zhu Man
- Qinghai University Affiliated Hospital, Xining, Qinghai Province
| | - Jing Hou
- Qinghai University Affiliated Hospital, Xining, Qinghai Province
| | - Li Sun
- Qinghai University Affiliated Hospital, Xining, Qinghai Province
| | - Meiyuan Tian
- Qinghai University Affiliated Hospital, Xining, Qinghai Province
| | - Yaogang Zhang
- Qinghai University Affiliated Hospital, Xining, Qinghai Province
| | - Jianhua Li
- Qinghai University Affiliated Hospital, Xining, Qinghai Province
| | - Yanyan Ma
- Qinghai University Affiliated Hospital, Xining, Qinghai Province
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39
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Fabrizi F, Cerutti R, Donato FM, Messa P. HBV infection is a risk factor for chronic kidney disease: Systematic review and meta-analysis. Rev Clin Esp 2020; 221:S0014-2565(19)30325-X. [PMID: 32037008 DOI: 10.1016/j.rce.2019.10.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2019] [Revised: 09/27/2019] [Accepted: 10/06/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND The activity of hepatitis B virus (HBV) as a risk factor for the incidence and progression of chronic kidney disease (CKD) has not been clarified. AIM We evaluated the impact of infection with HBV on the risk of CKD in the general population. MATERIAL AND METHODS We carried out a systematic review of the published medical literature to assess whether a relationship between hepatitis B infection and an increased risk of CKD in the adult general population occurs. We adopted the random effects model of DerSimonian and Laird to provide a summary estimate of the risk of chronic kidney disease (defined by lowered glomerular filtration rate and/or detectable proteinuria) with HBV infection across the published studies. Meta-regression and stratified analyses were also performed. RESULTS We retrieved 33 studies (n=7,849,849 patients) published in 26 different articles, and separate meta-analyses were performed according to the outcome. Pooling results from cohort studies (11 studies, n=1,056,645 patients) demonstrated a relationship between positive HBV serologic status and increased incidence of CKD, the summary estimate for adjusted HR with HBV across the surveys, 1.40 (95% CI, 1.16-1.69) (P<.001). Between-study heterogeneity was noted (Q value, 49.5, P<.0001). No relationship between HBV and prevalence of CKD was noted in the subset of cross-sectional studies (10 studies; n=3,222,545 patients), adjusted OR, 1.04 (95% IC 0.90-1.218; P=.5). Meta-regression analysis reported a relationship between positive HBsAg status and incidence of CKD in the general population (P<.015). CONCLUSIONS It appears that exposure to HBV infection seems to be associated with an increased risk of developing CKD in the adult general population. Studies aimed to understand the mechanisms responsible of such association are under way.
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Affiliation(s)
- F Fabrizi
- División de Nefrología, Hospital Maggiore, Fundación IRCCS, Milán, Italia.
| | - R Cerutti
- División de Nefrología, Hospital Maggiore, Fundación IRCCS, Milán, Italia
| | - F M Donato
- División de Gastroenterología, Hospital Maggiore, Fundación IRCCS, Milán, Italia
| | - P Messa
- División de Nefrología, Hospital Maggiore, Fundación IRCCS, Milán, Italia; Escuela Universitaria de Medicina, Milán, Italia
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Melendez QM, Wooten CJ, Krishnaji ST, Knagge K, Kirchner D, Lopez D. Identification of Novel Proteins Interacting with Proprotein Convertase Subtilisin/Kexin 9. INTERNATIONAL JOURNAL OF BIOMEDICAL INVESTIGATION 2020; 3:123. [PMID: 32587953 PMCID: PMC7316369 DOI: 10.31531/2581-4745.1000123] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
High levels of cholesterol, especially as low-density lipoprotein (LDL), are a well-known risk factor for atherosclerotic-related diseases. The key atherogenic property of LDL is its ability to form atherosclerotic plaque. Proprotein convertase subtilisin/kexin-9 (PCSK9) is an indirect regulator of plasma LDL levels by controlling the number of LDL receptor molecules expressed at the plasma membrane, especially in the liver. Herein, we performed a combination of affinity chromatography, mass spectrometry analysis and identification, and gene expression studies to identify proteins that interact with PCSK9. Through these studies, we identified three proteins, alpha-1-antitrypsin (A1AT), alpha-1-microglobulin/bikunin precursor (AMBP), and apolipoprotein H (APOH) expressed by C3A cells that interact with PCSK9. The expression levels of A1AT and APOH increased in cells treated with MITO+ medium, a condition previously shown to affect the function of PCSK9, as compared to treating with Regular (control) medium. However, AMBP expression did not change in response to the treatments. Additional studies are required to determine which of these proteins can modulate the expression/function of PCSK9. The identification of endogenous modulators of PCSK9's function could lead to the development of novel diagnostic tests or treatment options for patients suffering hypercholesterolemia in combination with other chronic metabolic diseases.
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Affiliation(s)
- Quantil M. Melendez
- Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technology Enterprise (BRITE), College of Arts and Sciences, North Carolina Central University, Durham, USA
| | - Catherine J. Wooten
- Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technology Enterprise (BRITE), College of Arts and Sciences, North Carolina Central University, Durham, USA
| | | | - Kevin Knagge
- David H Murdock Research Institute, Kannapolis, USA
| | | | - Dayami Lopez
- Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technology Enterprise (BRITE), College of Arts and Sciences, North Carolina Central University, Durham, USA
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41
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Wang CC, Cheng PN, Kao JH. Systematic review: chronic viral hepatitis and metabolic derangement. Aliment Pharmacol Ther 2020; 51:216-230. [PMID: 31746482 DOI: 10.1111/apt.15575] [Citation(s) in RCA: 78] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Revised: 08/08/2019] [Accepted: 10/17/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND The liver has a critical role in the metabolism of glucose and lipids. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection leads to a spectrum of liver disease including chronic hepatitis, cirrhosis and hepatocellular carcinoma. Metabolic syndrome (MetS) has a rising incidence owing to an epidemic of type 2 diabetes mellitus (T2DM) and obesity. Non-alcoholic fatty liver disease is a liver manifestation of MetS and has become the most common cause of chronic liver disease worldwide. AIM To summarise the interplay among hepatitis viruses, MetS and its components. METHODS We searched the literature about HBV, HCV infection, MetS, fatty liver and its components from PubMed. RESULTS With respect to the viral replication cycle, lipids are important mediators between viral entry and hepatocyte in HCV infection, but not in HBV infection. Thus, HCV infection is inversely associated with hyperlipidaemia and lipid rebound occurs following sustained viral response induced by interferon-based therapy or direct antiviral agents. In addition, HCV infection is positively associated with insulin resistance, hepatic steatosis, MetS and the risk of T2DM and atherosclerosis. In contrast, HBV infection may protect infected subjects from the development of MetS and hepatic steatosis. Accumulating evidence suggests that HBV infection is inversely associated with lipid metabolism, and exhibits no conclusive association with insulin resistance or the risk of T2DM and arteriosclerosis. CONCLUSIONS In patients with viral hepatitis and concurrent metabolic diseases, a multidisciplinary approach should be given rather than simply antiviral treatment.
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Affiliation(s)
- Chia-Chi Wang
- Department of Gastroenterology and Hepatology, Buddhist Tzu Chi Medical Foundation and School of Medicine, Taipei Tzu Chi Hospital, Tzu Chi University, Hualien, Taiwan
| | - Pin-Nan Cheng
- Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Internal Medicine, Department of Medical Research and Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
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Dächert C, Gladilin E, Binder M. Gene Expression Profiling of Different Huh7 Variants Reveals Novel Hepatitis C Virus Host Factors. Viruses 2019; 12:v12010036. [PMID: 31905685 PMCID: PMC7019296 DOI: 10.3390/v12010036] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Revised: 12/18/2019] [Accepted: 12/27/2019] [Indexed: 02/06/2023] Open
Abstract
Chronic Hepatitis C virus (HCV) infection still constitutes a major global health problem with almost half a million deaths per year. To date, the human hepatoma cell line Huh7 and its derivatives is the only cell line that robustly replicates HCV. However, even different subclones and passages of this single cell line exhibit tremendous differences in HCV replication efficiency. By comparative gene expression profiling using a multi-pronged correlation analysis across eight different Huh7 variants, we identified 34 candidate host factors possibly affecting HCV permissiveness. For seven of the candidates, we could show by knock-down studies their implication in HCV replication. Notably, for at least four of them, we furthermore found that overexpression boosted HCV replication in lowly permissive Huh7 cells, most prominently for the histone-binding transcriptional repressor THAP7 and the nuclear receptor NR0B2. For NR0B2, our results suggest a finely balanced expression optimum reached in highly permissive Huh7 cells, with even higher levels leading to a nearly complete breakdown of HCV replication, likely due to a dysregulation of bile acid and cholesterol metabolism. Our unbiased expression-profiling approach, hence, led to the identification of four host cellular genes that contribute to HCV permissiveness in Huh7 cells. These findings add to an improved understanding of the molecular underpinnings of the strict host cell tropism of HCV.
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Affiliation(s)
- Christopher Dächert
- Research Group “Dynamics of Early Viral Infection and the Innate Antiviral Response”, Division Virus-associated Carcinogenesis (F170), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany;
- Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany
| | - Evgeny Gladilin
- Division Bioinformatics and Omics Data Analytics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany;
- BioQuant, Heidelberg University, 69120 Heidelberg, Germany
| | - Marco Binder
- Research Group “Dynamics of Early Viral Infection and the Innate Antiviral Response”, Division Virus-associated Carcinogenesis (F170), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany;
- Correspondence: ; Tel.: +49-622-142-4974
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Fabrizi F, Cerutti R, Dixit V, Messa P. The impact of antiviral therapy for HCV on kidney disease: a systematic review and meta-analysis. Nefrologia 2019; 40:299-310. [PMID: 31813592 DOI: 10.1016/j.nefro.2019.07.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2019] [Revised: 06/28/2019] [Accepted: 07/15/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Controversy persists about the role of hepatitis C as a risk factor for developing kidney disease in the general population. Some authors have evaluated the effect of antiviral therapy for HCV on the risk of kidney disease. STUDY AIMS AND DESIGN A systematic review of the published medical literature was performed to assess whether antiviral therapy for HCV has an independent impact on kidney survival in the adult general population. A random effects model was used to generate an overall estimate of the risk of kidney disease after anti-HCV therapy across the published studies. Meta-regression and stratified analysis were also carried out. RESULTS Fifteen studies were eligible (n=356, 285 patients) and separate meta-analyses were conducted according to the outcome. Pooling studies based on viral responses (n=7; 34,763 individual patients) demonstrated a relationship between sustained viral response and lower frequency of kidney disease; the overall estimate for adjusted risk of kidney disease was 2.50 (95% CI, 1.41; 4.41) (p=0.0016) and between-study heterogeneity was found (p-value by Q test=0.004). Aggregation of studies comparing treated vs untreated cohorts (n=8, n=333,312 patients) revealed an association between anti-HCV therapy and lower risk of kidney disease. The overall estimate for adjusted risk of kidney disease across the eight studies was 0.39 (95% CI, 0.25; 0.612) (p=0.0001). Meta-regression showed that the effectiveness of antiviral therapy in reducing the frequency of kidney disease diminishes as cirrhosis (p=0.02) and HBV infection (p=0.0001) increase among HCV-infected individuals. CONCLUSIONS Antiviral therapy for HCV lowers the risk of kidney disease among HCV-infected individuals. Studies to understand the mechanisms underlying this association are ongoing.
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Affiliation(s)
- Fabrizio Fabrizi
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
| | - Roberta Cerutti
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Vivek Dixit
- Division of Gastroenterology, UCLA School of Medicine, CA, USA
| | - Piergiorgio Messa
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy; University School of Medicine, Milano, Italy
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Lin SY, Lin CL, Chen WS, Lin CC, Lin CH, Hsu WH, Hsu CY, Kao CH. Association Between Alcoholic Cirrhosis and Hemorrhagic Stroke: A Nationwide Population-based Study. Alcohol Alcohol 2019; 54:302-309. [PMID: 30957143 DOI: 10.1093/alcalc/agz025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 02/27/2019] [Accepted: 03/11/2019] [Indexed: 02/07/2023] Open
Abstract
AIMS This study investigated whether patients with alcoholic cirrhosis have a high risk of hemorrhagic stroke. METHODS In this study, 17,094 patients diagnosed with cirrhosis between 2000 and 2010 were identified using the Taiwan National Health Insurance claims data. Identified patients were randomly selected and propensity score matched with individuals without cirrhosis according to age, sex, comorbidities and index year. RESULTS The overall incidence rate of stroke was 4.41 and 12.1 per 1000 person-years in the chronic liver disease and cirrhosis (CLDC) with hepatitis B virus (HBV) or hepatitis C virus (HCV) cohort and the alcoholic CLDC cohort, respectively. The alcoholic CLDC cohort exhibited a 4.53-fold higher risk of hemorrhagic stroke (adjusted subhazard ratio [aSHR] = 4.53, 95% confidence interval [CI] = 3.05-6.71) than did the non-CLDC cohort, and the CLDC with HBV or HCV cohort exhibited a 1.40-fold higher risk of hemorrhagic stroke (aSHR = 1.40, 95% CI = 1.10-1.78) than did the non-CLDC cohort. The alcoholic CLDC cohort and the CLDC with HBV or HCV cohort showed an aSHR of 1.80 (95% CI = 1.36-2.40) and 0.95 (95% CI = 0.83-1.07) for ischemic stroke, respectively, compared with the non-CLDC cohort. CONCLUSION Alcoholic patients with CLDC had a higher risk of hemorrhagic stroke compared with non-alcoholic patients with CLDC and patients without CLDC.
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Affiliation(s)
- Shih-Yi Lin
- Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, Taiwan.,Division of Nephrology and Kidney Institute, China Medical University Hospital, Taichung, Taiwan
| | - Cheng-Li Lin
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan.,College of Medicine, China Medical University, Taichung, Taiwan
| | - Wei-Shan Chen
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan.,College of Medicine, China Medical University, Taichung, Taiwan
| | - Cheng-Chieh Lin
- Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, Taiwan.,Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chih-Hsueh Lin
- Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, Taiwan.,Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Wu-Huei Hsu
- Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, Taiwan.,Division of Pulmonary and Critical Care Medicine, China Medical University Hospital and China Medical University, Taichung, Taiwan
| | - Chung Y Hsu
- Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, Taiwan
| | - Chia-Hung Kao
- Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, Taiwan.,Department of Nuclear Medicine, China Medical University Hospital, Taichung, Taiwan.,Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan
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Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a major overall health predicament. Patients with HCV infection may progress to hepatic and extrahepatic complications. There are emerging groups of data on accelerated vascular changes triggering subclinical atherosclerosis. Nevertheless, whether these changes are associated with an increased risk of morbidity and mortality is unclear. AIM To determine subclinical arterial wall structural changes in noncirrhotic chronic hepatitis C patients and the impact of possible cofactors. PATIENTS AND METHODS Forty-two patients with noncirrhotic chronic HCV and 42 healthy controls matched in terms of age and sex were subjected to clinical, biochemical, and imaging measures for the evaluation of arterial wall changes (aortic elasticity/stiffness and carotid intima-media thickness). Elasticity was evaluated by measuring the aortic diameter and pulse wave velocity. RESULTS Nonsignificant greater mean aortic diameter was found among the cases than the control group (P = 0.67). The mean carotid intima-media thickness was quite similar in both groups (P = 0.12). The mean pulse wave velocity measures were twice those in the cases than the control group, indicating greater tendencies toward arterial stiffness among patients with HCV (P < 0.001). There was no significant relationship between any of the laboratory investigations (lipid and HCV-RNA values) and any of the vascular imaging investigations. CONCLUSION Aortic diameter and aortic stiffness are increased among chronic hepatitis C patients than healthy controls; however, there is no significant difference in carotid intima thickness.
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Davis JS, Young M, Lennox S, Jones T, Piera K, Pickles R, Oakley S. The effect of curing hepatitis C with direct-acting antiviral treatment on endothelial function. Antivir Ther 2019; 23:687-694. [PMID: 30048244 DOI: 10.3851/imp3257] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/19/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Epidemiological data suggest that chronic HCV infection (CHC) is associated with increased cardiovascular risk, but it is unknown if it is associated with endothelial dysfunction. We aimed to assess the effect of antiviral treatment on endothelial function in non-cirrhotic adults with CHC. METHODS Self-controlled before and after study. All patients had genotype-1 CHC and were treated with 12 weeks of paritaprevir/ritonavir, ombitasvir and dasabuvir (PrOD), with ribavirin added for those with genotype-1a infection. Endothelial function was assessed at three time points before antiviral treatment, at treatment weeks 1, 4, 8 and 12, and 12 weeks after the end of treatment. The main assessment tools were reactive hyperaemia peripheral arterial tonometry (RHPAT) and serum concentrations of angiopoietin-2 (Ang-2) and E-selectin. RESULTS A total of 16 patients were enrolled. Mean (sd) age was 51.4 (6.9) years and 11 participants (69%) were male. All 16 patients achieved a sustained virological response. The mean (sd) baseline RHPAT index was 2.05 (0.48), and there was no significant change during treatment (mean within-patient change from baseline to end of treatment =-0.23 [0.45]; P= not significant). There was a significant improvement in both mean Ang-2 (baseline 2.44 [0.79] ng/ml, within-patient change -0.60 [0.44]; P<0.001) and E-selectin (baseline 48.7 [21.5] ng/ml, within-patient change -14.4 [13.0]; P<0.001). CONCLUSIONS Removing HCV viraemia is associated with a significant improvement in endothelial function as measured by serum markers, but not in bedside microvascular reactivity. Chronic HCV viraemia may be associated with endothelial cell dysfunction and therefore long-term cardiovascular risk.
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Affiliation(s)
- Joshua S Davis
- Division of Medicine, John Hunter Hospital, Newcastle, NSW, Australia.,School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia.,Menzies School of Health Research, Darwin, NT, Australia
| | - Melissa Young
- Division of Medicine, John Hunter Hospital, Newcastle, NSW, Australia
| | - Sandra Lennox
- Division of Medicine, John Hunter Hospital, Newcastle, NSW, Australia
| | - Tracey Jones
- Division of Medicine, John Hunter Hospital, Newcastle, NSW, Australia
| | - Kim Piera
- Menzies School of Health Research, Darwin, NT, Australia
| | - Robert Pickles
- Division of Medicine, John Hunter Hospital, Newcastle, NSW, Australia.,School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
| | - Stephen Oakley
- Division of Medicine, John Hunter Hospital, Newcastle, NSW, Australia.,School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
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47
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Abd El Hafez MA, Kasemy ZAA. Effect of direct-acting antivirals on platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in patients with hepatitis C virus-related thrombocytopenia. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2019. [DOI: 10.4103/ejim.ejim_14_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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48
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Revuelto Artigas T, Zaragoza Velasco N, Gómez Arbones X, Vidal Ballester T, Piñol Felis C, Reñe Espinet J, Betriu Bars A. Chronic hepatitis C infection: An independent risk factor for subclinical atheromatosis. Rev Clin Esp 2019. [DOI: 10.1016/j.rceng.2019.02.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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49
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Cammarota S, Citarella A, Guida A, Conti V, Iannaccone T, Flacco ME, Bravi F, Naccarato C, Piscitelli A, Piscitelli R, Valente A, Calella G, Coppola N, Parruti G. The inpatient hospital burden of comorbidities in HCV-infected patients: A population-based study in two Italian regions with high HCV endemicity (The BaCH study). PLoS One 2019; 14:e0219396. [PMID: 31291351 PMCID: PMC6619769 DOI: 10.1371/journal.pone.0219396] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Accepted: 06/21/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND & AIMS Hepatitis C (HCV) is associated with several extrahepatic manifestations, and estimates of the hospitalization burden related to these comorbidities are still limited. The aim of this study is to quantify the hospitalization risk associated with comorbidities in an Italian cohort of HCV-infected patients and to assess which of these comorbidities are associated with high hospitalization resource utilization. METHODS Individuals aged 18 years and older with HCV-infection were identified in the Abruzzo's and Campania's hospital discharge abstracts during 2011-2014 with 1-year follow-up. Cardio-and cerebrovascular disease, diabetes and renal disease were grouped as HCV-related comorbidities. Negative binomial models were used to compare the hospitalization risk in patients with and without each comorbidity. Logistic regression model was used to identify the characteristics of being in the top 20% of patients with the highest hospitalization costs (high-cost patients). RESULTS 15,985 patients were included; 19.9% had a liver complication and 48.6% had one or more HCV-related comorbidities. During follow-up, 36.0% of patients underwent at least one hospitalization. Liver complications and the presence of two or more HCV-related comorbidities were the major predictors of hospitalization and highest inpatient costs. Among those, patients with cardiovascular disease had the highest risk of hospitalization (Incidence Rate Ratios = 1.42;95%CI:1.33-1.51) and the highest likelihood of becoming high-cost patients (Odd Ratio = 1.37;95%CI:1.20-1.57). CONCLUSION Beyond advanced liver disease, HCV-related comorbidities (especially cardiovascular disease) are the strongest predictors of high hospitalization rates and costs. Our findings highlight the potential benefit that early identification and treatment of HCV might have on the reduction of hospitalization costs driven by extrahepatic conditions.
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Affiliation(s)
- Simona Cammarota
- LinkHealth Health Economics, Outcomes & Epidemiology s.r.l., Naples, Italy
| | - Anna Citarella
- LinkHealth Health Economics, Outcomes & Epidemiology s.r.l., Naples, Italy
| | - Antonella Guida
- Directorate-General for Protection of Health, Campania Region, Naples, Italy
| | - Valeria Conti
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Baronissi (SA), Italy
| | - Teresa Iannaccone
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Baronissi (SA), Italy
| | | | | | - Cristina Naccarato
- Italian National Agency for New Technologies, Energy and Sustainable Economic Development “ENEA”, Bologna, Italy
| | - Antonella Piscitelli
- Specialisation School, Department of Pharmacy, University of Salerno, Fisciano, Italy
| | - Raffaele Piscitelli
- Specialisation School, Department of Pharmacy, University of Naples “Federico II”, Naples, Italy
| | - Alfredo Valente
- LinkHealth Health Economics, Outcomes & Epidemiology s.r.l., Naples, Italy
| | - Giulio Calella
- Infectious Diseases Unit, Pescara General Hospital, Pescara, Italy
| | - Nicola Coppola
- Infectious Diseases Unit, AORN Caserta, University of Campania “Luigi Vanvitelli”, Caserta, Italy
| | - Giustino Parruti
- Infectious Diseases Unit, Pescara General Hospital, Pescara, Italy
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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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