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McCary A, Sheu YS, Chesbrough K, Jonas MC. Improved Liver Fibrosis Regression After Direct-Acting Antiviral Therapy in Hepatitis C Patients: A Comparison of Patients With and Without MASLD. Clin Ther 2025:S0149-2918(25)00087-6. [PMID: 40287335 DOI: 10.1016/j.clinthera.2025.03.011] [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: 12/18/2024] [Revised: 03/12/2025] [Accepted: 03/23/2025] [Indexed: 04/29/2025]
Abstract
PURPOSE Chronic Hepatitis C (CHC) often results in liver fibrosis. Therefore, an important benefit of CHC treatment with direct-acting antiviral (DAA) medication is liver fibrosis regression. However, it is unclear how concurrent liver steatosis affects fibrosis regression following DAA therapy. Recent guidelines have defined liver steatosis associated with metabolic syndrome as metabolic dysfunction-associated steatotic liver disease (MASLD). We sought to examine the association of MASLD with the fibrosis regression benefits of DAA treatment for CHC. METHODS We conducted an observational retrospective analysis using electronic health records of patients aged 18-65 who completed DAA therapy for CHC from 2016 through 2022. FIB-4 scores were calculated during three time periods: just prior to DAA initiation, within 6 months post-DAA completion, and within 6-12 months post-DAA completion. These scores categorized liver fibrosis as high risk (>3.25), intermediate risk (1.45-3.25), or low risk (<1.45). An ordinal logistic regression model assessed the degree of fibrosis regression across these periods in CHC patients with and without MASLD. FINDINGS We identified 845 patients with CHC who received DAA therapy, of whom 225 met MASLD criteria. Both CHC patients with and without MASLD exhibited a decrease in FIB-4 category (coefficient = -0.361, P < 0.001) within the year following DAA therapy. The reduction in FIB-4 category post-treatment was more pronounced in the MASLD group compared to the non-MASLD group, as evidenced by a significant interaction between group and time period (coefficient = -0.439, P = 0.004). IMPLICATIONS In our cohort, MASLD was associated with greater liver fibrosis regression in the year following DAA therapy for CHC. This suggests that the concurrent presence of MASLD is not associated with diminished fibrosis regression from DAA therapy. Additional research is needed to determine the exact mechanism responsible for DAA-associated fibrosis regression in patients with MASLD.
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Affiliation(s)
- Alexis McCary
- Department of Gastroenterology, Mid-Atlantic Permanente Medical Group, Upper Marlboro, Maryland; Mid-Atlantic Permanente Research Institute, Mid-Atlantic Permanente Medical Group, Washington, District of Columbia.
| | - Yi-Shin Sheu
- Mid-Atlantic Permanente Research Institute, Mid-Atlantic Permanente Medical Group, Washington, District of Columbia
| | - Karen Chesbrough
- Mid-Atlantic Permanente Research Institute, Mid-Atlantic Permanente Medical Group, Washington, District of Columbia
| | - M Cabell Jonas
- Mid-Atlantic Permanente Research Institute, Mid-Atlantic Permanente Medical Group, Washington, District of Columbia
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Truscello E, Wang S, Young J, Sebastiani G, Walmsley SL, Hull M, Cooper C, Klein MB. Changes in Hepatic Steatosis Before and After Direct-Acting Antiviral Treatment in People With HIV and Hepatitis C Coinfection. J Infect Dis 2025; 231:e101-e112. [PMID: 39417816 PMCID: PMC11793071 DOI: 10.1093/infdis/jiae487] [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: 05/28/2024] [Revised: 09/09/2024] [Accepted: 10/04/2024] [Indexed: 10/19/2024] Open
Abstract
BACKGROUND Both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections increase the risk of hepatic steatosis (HS), which in turn contribute to the severity and progression of liver disease. Direct-acting antivirals (DAAs) can cure HCV but whether they reduce HS is unclear. METHODS HS was assessed using the controlled attenuation parameter (CAP) and the Hepatic Steatosis Index (HSI) in participants coinfected with HIV and HCV from the Canadian Coinfection Cohort. Changes in HS, before, during, and after successful DAA treatment were estimated using generalized additive mixed models, adjusted for covariates measured prior to treatment (age, sex, duration of HCV infection, body mass index, diabetes, prior exposure to dideoxynucleosides, and hazardous drinking). RESULTS In total, 431 participants with at least 1 measure of CAP or HSI before treatment were included. CAP steadily increased over time: adjusted annual slope 3.3 dB/m (95% credible interval [CrI], 1.6-4.9) before, and 3.9 dB/m (95% CrI, 1.9-5.9) after DAA treatment, irrespective of pretreatment CAP. In contrast, HSI changed little over time: annual slope 0.2 (95% CrI, -0.1 to 0.5) before and 0.2 (95% CrI, -0.1 to 0.5) after, but demonstrated a marked reduction during treatment -4.5 (95% CrI, -5.9 to -3.1). CONCLUSIONS When assessed by CAP, HS was unaffected by DAA treatment and steadily increased over time. In contrast, HSI did not appear to reflect changes in HS, with the decrease during treatment likely related to resolution of hepatic inflammation. Ongoing HS may pose a risk for liver disease in coinfected people cured of HCV.
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Affiliation(s)
- Esther Truscello
- Faculty of Health, Medicine, and Life Sciences, Maastricht University, Maastricht, The Netherlands
| | - Shouao Wang
- Department of Medicine, Division of Infectious Diseases, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
| | - Jim Young
- Department of Medicine, Division of Infectious Diseases, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
- Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada
| | - Giada Sebastiani
- Department of Medicine, Division of Infectious Diseases, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
- Division of Experimental Medicine, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Sharon L Walmsley
- University Health Network, University of Toronto, Toronto, Ontario, Canada
- Canadian Institutes of Health Research Canadian HIV Trials Network, Vancouver, British Columbia, Canada
| | - Mark Hull
- Department of Medicine, British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada
| | - Curtis Cooper
- Department of Medicine, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Marina B Klein
- Department of Medicine, Division of Infectious Diseases, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
- Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada
- Canadian Institutes of Health Research Canadian HIV Trials Network, Vancouver, British Columbia, Canada
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Wang MW, Lu LG. Current Status of Glucagon-like Peptide-1 Receptor Agonists in Metabolic Dysfunction-associated Steatotic Liver Disease: A Clinical Perspective. J Clin Transl Hepatol 2025; 13:47-61. [PMID: 39801787 PMCID: PMC11712088 DOI: 10.14218/jcth.2024.00271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 10/13/2024] [Accepted: 10/24/2024] [Indexed: 01/16/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently a pressing public health issue associated with adverse outcomes such as cirrhosis, malignancy, transplantation, and mortality. Lifestyle modifications constitute the most effective and fundamental management approach, but they often pose challenges in sustaining long-term clinical benefits. Hence, there is a critical need to enhance our understanding through pharmacological management, which unfortunately remains limited. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a leading treatment in the fields of diabetes and obesity, with recent preclinical and clinical studies indicating significant benefits in the management and treatment of MASLD. Our article begins by reviewing the beneficial therapeutic components of GLP-1RAs in MASLD. Subsequently, from a clinical research perspective, we concluded with the liver outcomes of current primary GLP-1RAs and co-agonists. Finally, we presented our insights on clinical concerns such as appropriate trial endpoints, management of comorbidities, and future developments. In conclusion, the benefits of GLP-1RAs in MASLD are promising, and background therapy involving metabolic modulation may represent one of the future therapeutic paradigms.
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Affiliation(s)
- Ming-Wang Wang
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lun-Gen Lu
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Darvishi M, Amiri R, Ghannad E, Mehrabkhani S, Rastgar N, Razaghi M, Bansal J, Chahar M, Rajput P, Saffarfar H, Ali-Khiavi P, Mobed A, Yazdani Y. Nanodiagnostics in global eradication of hepatitis C virus. Clin Chim Acta 2025; 565:120013. [PMID: 39447823 DOI: 10.1016/j.cca.2024.120013] [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: 09/16/2024] [Revised: 10/20/2024] [Accepted: 10/20/2024] [Indexed: 10/26/2024]
Abstract
Hepatitis C, caused by the hepatitis C virus (HCV), is a prevalent liver disease with severe outcomes, including cirrhosis and hepatocellular carcinoma. Traditional diagnostic methods primarily detect antiviral antibodies (anti-HCV) or viral RNA, but these approaches have limitations. Anti-HCV antibodies may take 2-4 weeks to develop in acute cases and can be absent in some individuals, leading to undiagnosed early-stage infections. This poses significant challenges for public health, particularly in resource-limited settings where early detection is crucial. This article explores the development of biosensors engineered to directly detect HCV surface antigens, such as envelope proteins. These biosensors provide a promising solution for earlier and more accurate diagnosis by identifying viral components at the initial stages of infection. By focusing on direct detection of viral antigens, these innovations could enhance early diagnosis, facilitate timely intervention, and reduce virus transmission. We evaluate the advancements in biosensor technology over the past decade and their potential to improve HCV detection in clinical and field settings, ultimately supporting global efforts to eliminate HCV as a public health threat.
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Affiliation(s)
- Mohammad Darvishi
- Darvishi M. Associate Professor of Infectious Disease, School of Aerospace and Subaquatic Medicine, Infectious Diseases & Tropical Medicine Research Center (IDTMC), AJA University of Medical Sciences, Tehran, Iran
| | - Reza Amiri
- Rajiv Gandhi University of Health Sciences, Bengaluru, Karnataka, India
| | - Emad Ghannad
- Faculty of Pharmacy, Guilan University of Medical Sciences
| | - Samir Mehrabkhani
- Rajiv Gandhi University of Health Sciences, Bengaluru, Karnataka, India
| | - Nassim Rastgar
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahkameh Razaghi
- Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences
| | - Jaya Bansal
- Chandigarh Pharmacy College, Chandigarh Group of Colleges, Jhanjeri, Mohali 140307, Punjab, India
| | - Mamata Chahar
- Department of Chemistry, NIMS Institute of Engineering & Technology, NIMS University Rajasthan, Jaipur, India
| | - Pranchal Rajput
- School of Applied and Life Sciences, Division of Research and Innovation, Uttaranchal University, Dehradun, India
| | - Hossein Saffarfar
- Cardiovascular Research Center, Tehran, Tehran University of Medical Sciences, Tehran, Iran
| | - Payam Ali-Khiavi
- Medical faculty, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ahmad Mobed
- Social Determinants of Health Research Center, Health Management and Safety Promotion Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Yalda Yazdani
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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Labidi A, Bensghaier R, Jebali S, Latrous L. Validated LC/MS method for simultaneous determination of elbasvir and grazoprevir in human plasma. ANNALES PHARMACEUTIQUES FRANÇAISES 2024; 82:1034-1045. [PMID: 38823440 DOI: 10.1016/j.pharma.2024.05.006] [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: 02/27/2024] [Revised: 04/14/2024] [Accepted: 05/27/2024] [Indexed: 06/03/2024]
Abstract
A sensitive and accurate LC/MS method for the determination of elbasvir (ELB) and grazoprevir (GZP) in human plasma was established using daclatasvir (DCT) as an internal standard. The analytes were separated on a Waters Spherisorb phenyl column (150mm×4.6mm ID, 5μm particle size) maintained at 40°C±2°C. Gradient elution, at a flow rate of 0.8mLmin-1, was used. The mobile phase consists of 90% of acetonitrile mixed to 10% of a 5mM ammonium formate buffer (+0.1% v/v of trimethylamine, pH was adjusted to 3.2 by formic acid) as phase A and 10% of acetonitrile mixed to 90% of the same buffer as phase B. Liquid-liquid extraction with ethyl acetate solvent was used to recuperate compounds from plasma. The method was validated over a concentration range of 2 and 100ng/mL for GZP and between 1 and 50ng/mL for ELB. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD)<15%, and the accuracy values ranged from 94.2 to 107.8%. The robustness of the method was established using a two-level full factorial design.
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Affiliation(s)
- Aymen Labidi
- Laboratoire National de Contrôle Des Médicaments, 11 bis, Rue Jebel Lakhdar Bab Saadoun, 1006 Tunis, Tunisia
| | - Rafika Bensghaier
- Laboratoire de Chimie Minérale Appliquée (LR19ES02), Faculté Des Sciences de Tunis, Université de Tunis El Manar, Campus Universitaire Farhat HACHED, 2092 Tunis, Tunisia; Laboratoire des Matériaux Composites et des Minéraux Argileux, Centre National de Recherches en Sciences des Matériaux Technopôle Borj Cedria, BP 73, 8027 Soliman, Tunisia
| | - Sami Jebali
- Institut National de Recherche et d'Analyse Physico-chimique, Laboratoire Matériaux Traitement et Analyse (LMTA), Biotechpole Sidi-Thabet, Ariana, Tunisia
| | - Latifa Latrous
- Laboratoire de Chimie Minérale Appliquée (LR19ES02), Faculté Des Sciences de Tunis, Université de Tunis El Manar, Campus Universitaire Farhat HACHED, 2092 Tunis, Tunisia; Institut Préparatoire Aux Études D'Ingénieurs El Manar, Université de Tunis El Manar, B.P. 244 El Manar II, 2092 Tunis, Tunisia.
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Behery ME, Elghwab A, Tabll AA, Elsayed EH, Abdelrazek MA. Serum collagen IV as a predictor for response to direct-acting antivirals hepatitis C therapy. J Immunoassay Immunochem 2024; 45:539-548. [PMID: 39402774 DOI: 10.1080/15321819.2024.2415882] [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] [Indexed: 11/12/2024]
Abstract
Althoughchronic hepatitis C (CHC) therapies based on direct-acting antiviral (DAA) agents safely improved treatment effectiveness, some cases do not obtain sustained virological response (SVR) and, thus, evaluating factors that may be related to treatment failure is very important. We aimed to evaluate the association of baseline serum collagen IV with DAA treatment failure in Egyptian patients with CHC. A total of 175 CHC patients (100 responders and 75non-responders tosofosbuvir/daclatasvir) were included. Collagen IV was assessed using sensitive chemiluminescent immunoassay. There was distinctly higher (P < 0.0001) collagen IV in non-responders compared to responder patients as the median (interquartile range) were 19.02 (13.4-25.2) vs.9.7 (7.2-12.3) µg/L, respectively. Collagen IV has a good ability for distinguishing nonresponders from responder patients (AUC = 0.890) with sensitivity of 92%, specificity 72%, PPV 71.1%, NPV 92.3% and accuracy of 80.6%. Collagen IV was correlated (p < 0.05) with decreased albumin (r=-0.266), elevated APRI (r = 0.288), and elevated FIB-4 (r = 0.281) scores. In conclusion,these findings suggested the remarkable role of baseline collagen IV in the prediction of HCV DAAs treatment response. Thus, however further studies are needed, its measurement may improve treatment duration and the disease control.
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Affiliation(s)
- Mohammed El Behery
- Chemistry Department, Faculty of Science, Port Said University, Port Said, Egypt
| | - AhmedI Elghwab
- Chemistry Department, Faculty of Science, Port Said University, Port Said, Egypt
| | - Ashraf A Tabll
- Microbial Biotechnology Department, Biotechnology Research Institute, National Research Centre, Giza, Egypt
| | - Elsherbiny H Elsayed
- Chemistry Department, Faculty of Science, Port Said University, Port Said, Egypt
| | - Mohamed A Abdelrazek
- Sherbin Central Hospital, Ministry of Health and Population, Shirbin, Egypt
- Research and Development Department, Biotechnology Research Center, New Damietta, Egypt
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Martín-Escolano R, Virseda-Berdices A, Berenguer J, González-García J, Brochado-Kith O, Fernández-Rodríguez A, Díez C, Hontañon V, Resino S, Jiménez-Sousa MÁ. Low plasma levels of BTLA and LAG-3 before HCV therapy are associated with metabolic disorders after HCV eradication in persons with HIV/HCV coinfection: a retrospective study. Front Pharmacol 2024; 15:1341612. [PMID: 39530457 PMCID: PMC11551606 DOI: 10.3389/fphar.2024.1341612] [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: 11/20/2023] [Accepted: 10/04/2024] [Indexed: 11/16/2024] Open
Abstract
Background Understanding the predictors of metabolic disorders in persons with HIV/HCV coinfection post-HCV therapy is crucial for improving patient outcomes. Since immune checkpoint proteins are usually upregulated in these persons with HIV/HCV coinfection, we aimed to evaluate the association between plasma immune checkpoint proteins at baseline (before HCV therapy) and metabolic disturbances during the follow-up (about 5 years after successful HCV treatment) in persons with HIV/HCV coinfection. Methods We performed a retrospective study on 80 persons with HIV/HCV coinfection with advanced fibrosis or cirrhosis who cleared HCV infection after successful HCV therapy and were followed for about 5 years after completion of HCV treatment. Plasma samples were collected at baseline. Immune checkpoint proteins were analyzed using a Luminex 200™ analyzer. Outcomes were the development of a metabolic event (type 2 diabetes mellitus and/or dyslipidemia) and the change in Triglycerides and glucose (TyG) index. Results During follow-up, 21 (26%) patients developed metabolic events (type 2 diabetes mellitus/dyslipidemia), and 29 (46.0%) patients had an increase in TyG during the follow-up. Low baseline values of BTLA and LAG-3, two immune checkpoint proteins, were associated with the development of metabolic events (aAMR = 0.69 and aAMR = 0.71, respectively) and with increases in TyG values (aAMR = 0.72 and aAMR = 0.70, respectively). In addition, other immune checkpoint proteins were also inversely associated with increases in TyG. Conclusion We discovered that low plasma levels of BTLA and LAG-3 before HCV therapy significantly correlate with an increased risk of developing metabolic disorders after treatment.
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Affiliation(s)
- Rubén Martín-Escolano
- Centro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Ana Virseda-Berdices
- Centro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Juan Berenguer
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Juan González-García
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Servicio de Medicina Interna-Unidad de VIH, Hospital Universitario La Paz, Madrid, Spain
- Instituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, Spain
| | - Oscar Brochado-Kith
- Centro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Amanda Fernández-Rodríguez
- Centro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Cristina Díez
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Victor Hontañon
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Servicio de Medicina Interna-Unidad de VIH, Hospital Universitario La Paz, Madrid, Spain
- Instituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, Spain
| | - Salvador Resino
- Centro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - María Ángeles Jiménez-Sousa
- Centro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
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Prata TVG, Dantas BP, Manchiero C, Nunes AKDS, de Paula VG, Tengan FM, Magri MC. Haplotype testing of MTTP alleles on insulin resistance in patients with chronic hepatitis C. GENE REPORTS 2024; 36:101951. [DOI: 10.1016/j.genrep.2024.101951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Mcotshana ZKS, Thwala LN, Tlomatsane MHC, van Steen E, Mthunzi-Kufa P. Recent advances in the development of multiplexed nanophotonic biosensors. Photodiagnosis Photodyn Ther 2024; 48:104246. [PMID: 38866068 DOI: 10.1016/j.pdpdt.2024.104246] [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: 02/22/2024] [Revised: 05/24/2024] [Accepted: 06/10/2024] [Indexed: 06/14/2024]
Abstract
The field of nanophotonics has advanced and can be utilized as a method to detect different infectious diseases. The introduction of multiplex nanophotonic diagnostics has enabled the speedy and simultaneous detection of viral infections and specific biomarkers. The quick reaction times, high sensitivity, and specificity of multiplex nanophotonic diagnostics enable real-time identification of viruses without the need for nucleic acid amplification. This review presents an overview of nanophotonic tools used to identify diseases and particular biomarkers. The paper also examines possible research areas for the development of unique, cutting-edge multiplex nanophotonic diagnostics capable of concurrently detecting various diseases or biomarkers/biomolecules. Furthermore, it discusses barriers to further advancement and offers insight into anticipated trends.
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Affiliation(s)
- Z K S Mcotshana
- National Laser Centre, Council for Scientific and Industrial Research, P.O. Box 395, Pretoria 0001, South Africa; Department of Chemical Engineering, University of Cape Town, South Ln, Rondebosch, Cape Town 7700, South Africa.
| | - L N Thwala
- National Laser Centre, Council for Scientific and Industrial Research, P.O. Box 395, Pretoria 0001, South Africa
| | - M H C Tlomatsane
- National Laser Centre, Council for Scientific and Industrial Research, P.O. Box 395, Pretoria 0001, South Africa; Department of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, South Ln, Rondebosch, Cape Town 7700, South Africa
| | - E van Steen
- Department of Chemical Engineering, University of Cape Town, South Ln, Rondebosch, Cape Town 7700, South Africa
| | - P Mthunzi-Kufa
- National Laser Centre, Council for Scientific and Industrial Research, P.O. Box 395, Pretoria 0001, South Africa; College of Agriculture, Engineering and Science, School of Chemistry and Physics, University of Kwa-Zulu Natal, University Road, Westville, Durban 3630, South Africa
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Méndez-Sánchez N, Coronel-Castillo CE, Ramírez-Mejía MM. Chronic Hepatitis C Virus Infection, Extrahepatic Disease and the Impact of New Direct-Acting Antivirals. Pathogens 2024; 13:339. [PMID: 38668294 PMCID: PMC11053783 DOI: 10.3390/pathogens13040339] [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: 03/06/2024] [Revised: 04/12/2024] [Accepted: 04/14/2024] [Indexed: 04/29/2024] Open
Abstract
Chronic hepatitis C virus infection is an important cause of liver cirrhosis, hepatocellular carcinoma and death. Furthermore, it is estimated that about 40-70% of patients develop non-hepatic alterations in the course of chronic infection. Such manifestations can be immune-related conditions, lymphoproliferative disorders and metabolic alterations with serious adverse events in the short and long term. The introduction of new Direct-Acting Antivirals has shown promising results, with current evidence indicating an improvement and remission of these conditions after a sustained virological response.
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Affiliation(s)
- Nahum Méndez-Sánchez
- Unit Liver Research, Medica Sur Clinic & Foundation, Mexico City 14050, Mexico;
- Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico
| | | | - Mariana Michelle Ramírez-Mejía
- Unit Liver Research, Medica Sur Clinic & Foundation, Mexico City 14050, Mexico;
- Plan of Combined Studies in Medicine (PECEM MD/PhD), Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico
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Yang TH, Gao WC, Ma X, Liu Q, Pang PP, Zheng YT, Jia Y, Zheng CB. A Review on The Pathogenesis of Cardiovascular Disease of Flaviviridea Viruses Infection. Viruses 2024; 16:365. [PMID: 38543730 PMCID: PMC10974792 DOI: 10.3390/v16030365] [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: 01/13/2024] [Revised: 02/20/2024] [Accepted: 02/25/2024] [Indexed: 05/23/2024] Open
Abstract
Members of the Flaviviridae family, encompassing the Flavivirus and Hepacivirus genera, are implicated in a spectrum of severe human pathologies. These diseases span a diverse spectrum, including hepatitis, vascular shock syndrome, encephalitis, acute flaccid paralysis, and adverse fetal outcomes, such as congenital heart defects and increased mortality rates. Notably, infections by Flaviviridae viruses have been associated with substantial cardiovascular compromise, yet the exploration into the attendant cardiovascular sequelae and underlying mechanisms remains relatively underexplored. This review aims to explore the epidemiology of Flaviviridae virus infections and synthesize their cardiovascular morbidities. Leveraging current research trajectories and our investigative contributions, we aspire to construct a cogent theoretical framework elucidating the pathogenesis of Flaviviridae-induced cardiovascular injury and illuminate prospective therapeutic avenues.
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Affiliation(s)
- Tie-Hua Yang
- School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, China; (T.-H.Y.); (P.-P.P.)
- Key Laboratory of Animal Models and Human Diseases Mechanisms of Chinese Academy of Sciences, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, China; (X.M.); (Y.-T.Z.)
- Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
| | - Wen-Cong Gao
- School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China;
| | - Xin Ma
- Key Laboratory of Animal Models and Human Diseases Mechanisms of Chinese Academy of Sciences, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, China; (X.M.); (Y.-T.Z.)
- College of Modern Biomedical Industry, Kunming Medical University, Kunming 650500, China
| | - Qian Liu
- School of Pharmacy, Chongqing Medical University, Chongqing 400016, China;
| | - Pan-Pan Pang
- School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, China; (T.-H.Y.); (P.-P.P.)
- Key Laboratory of Animal Models and Human Diseases Mechanisms of Chinese Academy of Sciences, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, China; (X.M.); (Y.-T.Z.)
| | - Yong-Tang Zheng
- Key Laboratory of Animal Models and Human Diseases Mechanisms of Chinese Academy of Sciences, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, China; (X.M.); (Y.-T.Z.)
- Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
| | - Yinnong Jia
- School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China;
| | - Chang-Bo Zheng
- School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China;
- College of Modern Biomedical Industry, Kunming Medical University, Kunming 650500, China
- Yunnan Vaccine Laboratory, Kunming 650500, China
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12
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Ding Y, Zhang P, Deng T, Yan X, Zhang M, Xie Z, Huang G, Wang P, Cai T, Zhang X, Xiao X, Xia Y, Liu B, Peng Y, Tang X, Hu M, Xiao Y, Li X, Clercq ED, Li G, Zhou Z. Association of human leukocyte antigen (HLA) footprints with the comorbidity of latent autoimmune diabetes in adults (LADA) and hepatitis C virus (HCV) infection: A multicenter cross-sectional study. Diabetes Metab Syndr 2024; 18:102939. [PMID: 38181721 DOI: 10.1016/j.dsx.2023.102939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 12/26/2023] [Accepted: 12/27/2023] [Indexed: 01/07/2024]
Abstract
AIMS This study aims to investigate the interplay between hepatitis C virus (HCV) infection and major forms of diabetes: type 1 diabetes (T1D), type 2 diabetes (T2D), and latent autoimmune diabetes in adults (LADA). METHODS This multicenter study analyzed a cohort of 2699 diabetic and 7344 non-diabetic subjects who visited medical centers in China from 2014 to 2021. T1D, T2D, LADA, and HCV were diagnosed using standard procedures. High-throughput sequencing was conducted to identify genetic footprints of human leukocyte antigen (HLA) alleles and haplotypes at the DRB1, DQA1, and DQB1 loci. RESULTS HCV infection was detected in 3 % (23/766) of LADA patients, followed by 1.5 % (15/977) of T2D patients, 1.4 % (13/926) of T1D patients, and 0.5 % (38/7344) of non-diabetic individuals. HCV prevalence was significantly higher in people with diabetes than in non-diabetic individuals (p < 0.01). HLA alleles (DQB1*060101, DQB1*040101) and haplotypes (DRB1*080302-DQA1*010301-DQB1*060101) in LADA patients with HCV revealed higher frequencies than in LADA patients without HCV (adjusted p < 0.03). Furthermore, a higher risk of diabetes complications was found among LADA patients with HCV infection (p < 0.001). CONCLUSIONS LADA patients are susceptible to HCV infection, potentially associated with certain HLA alleles/haplotypes. Early diagnosis and treatment of HCV infection among people with diabetes are important for the management of severe complications.
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Affiliation(s)
- Yujin Ding
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Ministry of Education), Metabolic Syndrome Research Center, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Pan Zhang
- Xiangya School of Public Health, Hunan Children's Hospital Affiliated with The Xiangya School of Medicine, Central South University, Changsha, China
| | - Tuo Deng
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Ministry of Education), Metabolic Syndrome Research Center, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Xiang Yan
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Ministry of Education), Metabolic Syndrome Research Center, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Min Zhang
- Department of Hepatology and Infectious Diseases, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Zhiguo Xie
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Ministry of Education), Metabolic Syndrome Research Center, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Gan Huang
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Ministry of Education), Metabolic Syndrome Research Center, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Ping Wang
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Ministry of Education), Metabolic Syndrome Research Center, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Ting Cai
- Xiangya School of Public Health, Hunan Children's Hospital Affiliated with The Xiangya School of Medicine, Central South University, Changsha, China
| | - Xiaoli Zhang
- Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany
| | - Xinqiang Xiao
- Department of Hepatology and Infectious Diseases, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Ying Xia
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Ministry of Education), Metabolic Syndrome Research Center, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Bingwen Liu
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Ministry of Education), Metabolic Syndrome Research Center, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Ya Peng
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Ministry of Education), Metabolic Syndrome Research Center, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Xiaohan Tang
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Ministry of Education), Metabolic Syndrome Research Center, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Min Hu
- Department of Clinical Laboratory, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Yang Xiao
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Ministry of Education), Metabolic Syndrome Research Center, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Xia Li
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Ministry of Education), Metabolic Syndrome Research Center, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Erik De Clercq
- Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium
| | - Guangdi Li
- Xiangya School of Public Health, Hunan Children's Hospital Affiliated with The Xiangya School of Medicine, Central South University, Changsha, China.
| | - Zhiguang Zhou
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Ministry of Education), Metabolic Syndrome Research Center, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.
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13
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Malaina I, Martinez L, Salcines-Cuevas D, Teran-Navarro H, Ocejo-Vinyals JG, Gonzalez-Lopez E, Soriano V, Ubeda M, Perez Pinilla MB, Martinez de la Fuente I, Alvarez-Dominguez C. Testing a vaccine candidate against Hepatitis C virus designed by combinatorial optimization. Sci Rep 2023; 13:21746. [PMID: 38066027 PMCID: PMC10709393 DOI: 10.1038/s41598-023-48458-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 11/27/2023] [Indexed: 12/18/2023] Open
Abstract
This paper presents a new procedure for vaccine design against highly variable viruses such as Hepatitis C. The procedure uses an optimization algorithm to design vaccines that maximize the coverage of epitopes across different virus variants. Weighted epitopes based on the success ratio of immunological assays are used to prioritize the selection of epitopes for vaccine design. The procedure was successfully applied to design DC vaccines loaded with two HCV peptides, STG and DYP, which were shown to be safe, immunogenic, and able to induce significant levels of anti-viral cytokines, peptide-specific cellular immune responses and IgG antibodies. The procedure could potentially be applied to other highly variable viruses that currently lack effective vaccines.
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Affiliation(s)
- Iker Malaina
- Department of Mathematics, University of the Basque Country (UPV/EHU), 48080, Bilbao, Spain.
- Biocruces Health Research Institute, Bilbao, Spain.
| | - Luis Martinez
- Department of Mathematics, University of the Basque Country (UPV/EHU), 48080, Bilbao, Spain
- Biocruces Health Research Institute, Bilbao, Spain
- Basque Center of Applied Mathematics (BCAM), 48009, Bilbao, Spain
| | - David Salcines-Cuevas
- Facultad de Ciencias de La Salud, Universidad Internacional de La Rioja (UNIR), MEDONLINE Group, Avda. de La Paz, 137, 26006, Logroño, La Rioja, Spain
| | - Hector Teran-Navarro
- Facultad de Ciencias de La Salud, Universidad Internacional de La Rioja (UNIR), MEDONLINE Group, Avda. de La Paz, 137, 26006, Logroño, La Rioja, Spain
| | - J Gonzalo Ocejo-Vinyals
- Servicio de Inmunología, Cantabria and Instituto de Investigación Marqués de Valdecilla (IDIVAL), Hospital Universitario Marqués de Valdecilla, Avda. de Valdecilla S/N, 39008, Santander, Spain
| | - Elena Gonzalez-Lopez
- Servicio de Inmunología, Cantabria and Instituto de Investigación Marqués de Valdecilla (IDIVAL), Hospital Universitario Marqués de Valdecilla, Avda. de Valdecilla S/N, 39008, Santander, Spain
| | - Vicente Soriano
- Facultad de Ciencias de La Salud, Universidad Internacional de La Rioja (UNIR), MEDONLINE Group, Avda. de La Paz, 137, 26006, Logroño, La Rioja, Spain
| | - María Ubeda
- Facultad de Ciencias de La Salud, Universidad Internacional de La Rioja (UNIR), MEDONLINE Group, Avda. de La Paz, 137, 26006, Logroño, La Rioja, Spain
| | | | | | - Carmen Alvarez-Dominguez
- Facultad de Ciencias de La Salud, Universidad Internacional de La Rioja (UNIR), MEDONLINE Group, Avda. de La Paz, 137, 26006, Logroño, La Rioja, Spain.
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14
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Tronina O, Brzdęk M, Zarębska-Michaluk D, Lorenc B, Janocha-Litwin J, Berak H, Sitko M, Dybowska D, Mazur W, Tudrujek-Zdunek M, Janczewska E, Klapaczyński J, Dobracki W, Parfieniuk-Kowerda A, Krygier R, Socha Ł, Flisiak R. Real-world effectiveness of genotype-specific and pangenotypic direct-acting antivirals in HCV-infected patients with renal failure. Clin Exp Hepatol 2023; 9:320-334. [PMID: 38774196 PMCID: PMC11103803 DOI: 10.5114/ceh.2023.133307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 11/16/2023] [Indexed: 05/24/2024] Open
Abstract
Aim of the study The aim is to summarize the effectiveness and safety of genotype-specific and pangenotypic hepatitis C virus (HCV) treatments in patients with renal failure. Material and methods In the EpiTer-2 database, which includes data from 22 hepatology centers in Poland, 593 patients with HCV infection and kidney failure were identified. According to KDIGO 2022, they fulfilled the criteria of chronic kidney disease. Patients were divided into two groups: treated with genotype-specific regimens (n = 428) and pangenotypic options (n = 165), in relation to the stage of kidney disease determined using the glomerular filtration rate (GFR) (Cockcroft and Gault equation). Two separate groups were created for hemodialyzed patients (n = 134) and patients after kidney transplantation (n = 89). Results In a total of 593 patients, 78.7% were treatment-naïve and 23.9% had liver cirrhosis, in 27.5% of cases decompensated. In both groups, the dominant genotype was GT1b. Among patients treated with genotype-specific regimens, LDV/SOF ± RBV, OBV/PTV/r + DSV ± RBV, and GZR/EBR ± RBV treatments were given to 31.5%, 31.5%, and 34.8% of patients respectively. In pangenotypic regimens, GLE/PIB was chosen in 50.3%. Ninety-six percent and 98.8% of patients in the genotype-specific regimen and 88.5% and 94.8% in the pangenotypic regimen achieved a sustained virologic response at 12 weeks (SVR12) in the intention-to-treat and per protocol population respectively. Liver cirrhosis was identified as a risk factor for virological failure. During the study, 14 patients died, 7 in each of the two groups, none related to the antiviral treatment. Conclusions Both types of treatment regimens are equally effective and safe in patients with renal failure. The stage of renal failure or transplant does not influence the antiviral response.
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Affiliation(s)
- Olga Tronina
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland
| | | | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Medical University Gdańsk, Gdańsk, Poland
| | - Justyna Janocha-Litwin
- Department of Infectious Diseases and Hepatology, Wrocław Medical University, Wrocław, Poland
| | - Hanna Berak
- Outpatient Clinic, Hospital for Infectious Diseases in Warsaw, Warsaw, Poland
| | - Marek Sitko
- Department of Infectious and Tropical Diseases, Jagiellonian University, Kraków, Poland
| | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Nicolaus Copernicus University, Bydgoszcz, Poland
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases, Medical University of Silesia, Chorzów, Poland
| | | | - Ewa Janczewska
- Department of Basic Medical Sciences, School of Public Health in Bytom, Medical University of Silesia, Katowice, Poland
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, The National Institute of Medicine of the Ministry of Interior and Administration, Warsaw, Poland
| | | | - Anna Parfieniuk-Kowerda
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland
| | - Rafał Krygier
- Outpatients Hepatology Department, NZOZ GEMINI, Żychlin, Poland
| | - Łukasz Socha
- Department of Infectious Diseases, Hepatology, and Liver Transplantation, Pomeranian Medical University, Szczecin, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland
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15
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Biagi F, Carlomagno F, Carbone M, Veralli R, Vespasiani-Gentilucci U, Riva E, Manfrini S, Tuccinardi D, De Santis A, Gnessi L, Watanabe M. Fibroblast Growth Factor 21 in Chronic Hepatitis C: A Potential Non-Invasive Biomarker of Liver Status upon Viral Eradication. Metabolites 2023; 13:1119. [PMID: 37999215 PMCID: PMC10673401 DOI: 10.3390/metabo13111119] [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: 09/25/2023] [Revised: 10/26/2023] [Accepted: 10/27/2023] [Indexed: 11/25/2023] Open
Abstract
Fibroblast growth factor 21 (FGF-21), previously recognized as a marker of liver damage and a potential drug target in non-alcoholic fatty liver disease (NAFLD), has unclear implications in hepatitis C virus (HCV) infections. This study aimed to investigate the relationship between FGF-21 levels and liver health in patients with HCV undergoing direct-acting antiviral (DAA) treatment. Forty-five patients were assessed for liver stiffness, blood chemistry, and other relevant metrics before and after achieving sustained viral response (SVR), defined as the absence of detectable HCV-RNA after 24 weeks of treatment. Post-treatment, all patients showed a decrease in liver stiffness and improved liver enzyme levels (AST and ALT), alongside an increase in FGF-21 levels. Interestingly, the increase in FGF-21 correlated negatively with liver stiffness but showed no correlation with hepatic steatosis. The observed elevation in FGF-21 levels at SVR following DAA therapy for chronic HCV infection can be attributed to the restoration of hepatic function, including its synthetic capabilities. Specifically, the mitigation of liver fibrosis post-HCV eradication is expected to lead to improvements in liver function, such as enhanced albumin and FGF-21 production. This improvement in synthetic function likely drives the increase in FGF-21 levels, rather than changes in liver fat content. We suggest a potential role of FGF-21 as a marker of fibrosis and hepatic cytotoxicity and as a drug target beyond NAFLD, to be confirmed by additional studies.
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Affiliation(s)
- Filippo Biagi
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161 Rome, Italy (F.C.); (M.W.)
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
| | - Francesco Carlomagno
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161 Rome, Italy (F.C.); (M.W.)
| | - Martina Carbone
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy (A.D.S.)
- Department of General Surgery, Section of Gastroenterology, Azienda Sanitaria Universitaria Friuli Centrale–P.O. Santa Maria della Misericordia di Udine, 33100 Udine, Italy
| | - Roberta Veralli
- Clinical Laboratory Unit, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy;
- Unit of Virology, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy
| | | | - Elisabetta Riva
- Unit of Virology, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy
- Department of Medicine and Surgery, Campus Bio-Medico University of Rome, 00128 Rome, Italy
| | - Silvia Manfrini
- Department of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, 00128 Rome, Italy
| | - Dario Tuccinardi
- Department of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, 00128 Rome, Italy
| | - Adriano De Santis
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy (A.D.S.)
| | - Lucio Gnessi
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161 Rome, Italy (F.C.); (M.W.)
| | - Mikiko Watanabe
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161 Rome, Italy (F.C.); (M.W.)
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16
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Dudina KR, Belyy PA, Maev IV, Klimova EA, Shutko SA, Znoyko OO, Yuschuk ND. [Assessment of body mass index in patients with chronic hepatitis C who received an effective antiviral therapy]. TERAPEVT ARKH 2023; 95:634-640. [PMID: 38158898 DOI: 10.26442/00403660.2023.08.202318] [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: 10/10/2023] [Accepted: 10/10/2023] [Indexed: 01/03/2024]
Abstract
AIM To evaluate the body mass index (BMI) in patients with chronic hepatitis C (CHC) with different stages of liver fibrosis and steatosis who received effective antiviral therapy (AVT). MATERIALS AND METHODS The study included 278 CHC patients with a sustained virologic response (SVR) at the end of treatment. In addition to assessing the investigational data to determine the clinical status of the patient, we calculated BMI (following the World Health Organization guidelines) and determined the severity of liver fibrosis (F) and steatosis (S) using transient elastography. The patients were assessed at the start of antiviral therapy, after ≥6 months from the moment SVR was confirmed, and then every 12 to 24 months. RESULTS By the end of the study, the mean patient age was 49 years, 53% of them were men, and 34% of the patients were obese. Excessive weight gain was registered in 17% (n=48) of the cases, with 60% newly diagnosed with Class 1 to 2 obesity. Both before the start of AVT and years after reaching SVR, the mean BMI corresponded to the reference pre-obesity values, the liver steatosis was significantly more often absent in normal BMI; on the contrary, fatty liver (predominantly S2 to S3) was registered in individuals with elevated BMI (p<0.0001). After the long-term period following a successful therapy, Stage F4 liver fibrosis patients were mainly diagnosed with obesity (80% versus 44% before AVT; p=0.0010). CONCLUSION The high proportion of patients with elevated BMI and liver steatosis seen years after a successful CHC therapy indicates a continued risk of progression of chronic liver disease. Such patients should be advised on how important it is to change their lifestyle to reduce overweight and prevent weight gain. We also need long-term assessments of how liver steatosis changes over time and what are the outcomes associated with post-SVR increase in BMI.
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Affiliation(s)
- K R Dudina
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - P A Belyy
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - I V Maev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - E A Klimova
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - S A Shutko
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - O O Znoyko
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - N D Yuschuk
- Yevdokimov Moscow State University of Medicine and Dentistry
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17
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Wang X, Cao Y, Guo J, Li D, Zhang H, Song Q, Lu J. Association between MTTP genotype (-493G/T) polymorphism and hepatic steatosis in hepatitis C: a systematic review and meta-analysis. Lipids Health Dis 2023; 22:154. [PMID: 37726765 PMCID: PMC10507831 DOI: 10.1186/s12944-023-01916-x] [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: 05/28/2023] [Accepted: 09/03/2023] [Indexed: 09/21/2023] Open
Abstract
BACKGROUND Hepatitis C has been associated with the development of hepatic steatosis, which increases the risk of liver cancer. The microsomal triglyceride transporter protein (MTTP), is a lipid transport protein that mediates lipid metabolism and CD1d antigen presentation. The study aimed to explore the association between MTTP genotype (-493G/T) polymorphism and hepatic steatosis in hepatitis C. METHODS The database "Pubmed, Cochrane library, CNKI, Web of science, Embase and CBM" were retrieved to identify the literature. The quality of the selected literature was evaluated using the "the Newcastle-Ottawa Scale" (NOS). Relevant data was extracted and analyzed using the Stata software. Heterogeneity was expressed by "Cochran's Q and I2", with I2 ≥ 50% or P < 0.05 indicating high heterogeneity. A random-effects model and subgroup analysis were conducted to identify the sources of heterogeneity. We also used "Funnel plots", "Egger's tests" and "Begg's tests" to evaluate biases in the literature. RESULTS The study found a significant and positive association between liver steatosis and the HCV genotype 3 with a dominant model of the MTTP genotype (-493G/T) (OR = 11.57, 95%CI: 4.467-29.962, P < 0.001). In contrast, no correlation was found between hepatic steatosis and either the recessive, homozygous or heterozygous models (OR = 1.142, P = 0.5; OR = 1.581, P = 0.081; OR = 1.029, P = 0.86). There was no significant publication biases, as measured by the Funnel plot, and the Egger's and Begg's tests. Finally, sensitivity analysis showed the obtained results are stable. CONCLUSIONS Dominant mutations in the T allele of the MTTP genotype (-493G/T) increase susceptibility to hepatic steatosis in patients presenting with the HCV genotype 3.
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Affiliation(s)
- Xiaoxia Wang
- Department of Medical Oncology, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Yu Cao
- Department of Clinical Epidemiology Research, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Jia Guo
- Department of Medical Oncology, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Dezhao Li
- Department of Medical Oncology, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Haitao Zhang
- Department of Hepatobiliary Surgery and Liver Transplantation Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Qingkun Song
- Department of Clinical Epidemiology Research, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Jun Lu
- Department of Medical Oncology, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
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Grossini E, Smirne C, Venkatesan S, Tonello S, D'Onghia D, Minisini R, Cantaluppi V, Sainaghi PP, Comi C, Tanzi A, Bussolati B, Pirisi M. Plasma Pattern of Extracellular Vesicles Isolated from Hepatitis C Virus Patients and Their Effects on Human Vascular Endothelial Cells. Int J Mol Sci 2023; 24:10197. [PMID: 37373343 DOI: 10.3390/ijms241210197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 06/08/2023] [Accepted: 06/13/2023] [Indexed: 06/29/2023] Open
Abstract
Hepatitis C virus (HCV) patients are at increased risk of cardiovascular disease (CVD). In this study, we aimed to evaluate the role of extracellular vesicles (EVs) as pathogenic factors for the onset of HCV-related endothelial dysfunction. Sixty-five patients with various stages of HCV-related chronic liver disease were enrolled in this case series. Plasma EVs were characterized and used to stimulate human vascular endothelial cells (HUVEC), which were examined for cell viability, mitochondrial membrane potential, and reactive oxygen species (ROS) release. The results showed that EVs from HCV patients were mainly of endothelial and lymphocyte origin. Moreover, EVs were able to reduce cell viability and mitochondrial membrane potential of HUVEC, while increasing ROS release. Those harmful effects were reduced by the pretreatment of HUVEC with the NLR family pyrin domain containing 3 (NLRP3)/AMP-activated protein kinase and protein kinase B blockers. In conclusion, in HCV patients, we could highlight a circulating pattern of EVs capable of inducing damage to the endothelium. These data represent a novel possible pathogenic mechanism underlying the reported increase of CVD occurrence in HCV infection and could be of clinical relevance also in relation to the widespread use of antiviral drugs.
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Affiliation(s)
- Elena Grossini
- Laboratory of Physiology, Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy
| | - Carlo Smirne
- Internal Medicine Unit, Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy
- Maggiore della Carità Hospital, 28100 Novara, Italy
| | - Sakthipriyan Venkatesan
- Laboratory of Physiology, Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy
| | - Stelvio Tonello
- Internal Medicine Unit, Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy
- Maggiore della Carità Hospital, 28100 Novara, Italy
| | - Davide D'Onghia
- Internal Medicine Unit, Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy
- Maggiore della Carità Hospital, 28100 Novara, Italy
| | - Rosalba Minisini
- Internal Medicine Unit, Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy
- Maggiore della Carità Hospital, 28100 Novara, Italy
| | - Vincenzo Cantaluppi
- Nephrology Unit, Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy
| | - Pier Paolo Sainaghi
- Internal Medicine Unit, Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy
- CAAD-Center for Autoimmune and Allergic Diseases, and IRCAD-Interdisciplinary Research Center for Autoimmune Diseases, Università del Piemonte Orientale, 28100 Novara, Italy
| | - Cristoforo Comi
- Neurology Unit, Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy
- Sant'Andrea Hospital, 13100 Vercelli, Italy
| | - Adele Tanzi
- Molecular Biotechnology Center "Guido Tarone", Department of Molecular Biotechnology and Health Sciences, University of Torino, 10124 Turin, Italy
| | - Benedetta Bussolati
- Molecular Biotechnology Center "Guido Tarone", Department of Molecular Biotechnology and Health Sciences, University of Torino, 10124 Turin, Italy
| | - Mario Pirisi
- Internal Medicine Unit, Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy
- Maggiore della Carità Hospital, 28100 Novara, Italy
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Islam KU, Anwar S, Patel AA, Mirdad MT, Mirdad MT, Azmi MI, Ahmad T, Fatima Z, Iqbal J. Global Lipidome Profiling Revealed Multifaceted Role of Lipid Species in Hepatitis C Virus Replication, Assembly, and Host Antiviral Response. Viruses 2023; 15:v15020464. [PMID: 36851679 PMCID: PMC9965260 DOI: 10.3390/v15020464] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 01/29/2023] [Accepted: 02/01/2023] [Indexed: 02/11/2023] Open
Abstract
Hepatitis C virus (HCV) is a major human pathogen that requires a better understanding of its interaction with host cells. There is a close association of HCV life cycle with host lipid metabolism. Lipid droplets (LDs) have been found to be crucial organelles that support HCV replication and virion assembly. In addition to their role in replication, LDs also have protein-mediated antiviral properties that are activated during HCV infection. Studies have shown that HCV replicates well in cholesterol and sphingolipid-rich membranes, but the ways in which HCV alters host cell lipid dynamics are not yet known. In this study, we performed a kinetic study to check the enrichment of LDs at different time points of HCV infection. Based on the LD enrichment results, we selected early and later time points of HCV infection for global lipidomic study. Early infection represents the window period for HCV sensing and host immune response while later infection represents the establishment of viral RNA replication, virion assembly, and egress. We identified the dynamic profile of lipid species at early and later time points of HCV infection by global lipidomic study using mass spectrometry. At early HCV infection, phosphatidylinositol phospholipids (PIPs), lysophosphatidic acid (LPA), triacyl glycerols (TAG), phosphatidylcholine (PC), and trihexosylceramides (Hex3Cer) were observed to be enriched. Similarly, free fatty acids (FFA), phosphatidylethanolamine (PE), N-acylphosphatidylethanolamines (NAPE), and tri acylglycerols were enriched at later time points of HCV infection. Lipids enriched at early time of infection may have role in HCV sensing, viral attachment, and immune response as LPA and PIPs are important for immune response and viral attachment, respectively. Moreover, lipid species observed at later infection may contribute to HCV replication and virion assembly as PE, FFA, and triacylglycerols are known for the similar function. In conclusion, we identified lipid species that exhibited dynamic profile across early and later time points of HCV infection compared to mock cells, which could be therapeutically relevant in the design of more specific and effective anti-viral therapies.
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Affiliation(s)
- Khursheed Ul Islam
- Multidisciplinary Center for Advanced Research and Studies, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
| | - Saleem Anwar
- Multidisciplinary Center for Advanced Research and Studies, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
| | - Ayyub A. Patel
- Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha 62529, Saudi Arabia
| | | | | | - Md Iqbal Azmi
- Multidisciplinary Center for Advanced Research and Studies, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
| | - Tanveer Ahmad
- Multidisciplinary Center for Advanced Research and Studies, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
| | - Zeeshan Fatima
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Bisha, Bisha 61922, Saudi Arabia
- Amity Institute of Biotechnology, Amity University Haryana, Manesar, Gurugram 122413, India
- Correspondence: (Z.F.); (J.I.)
| | - Jawed Iqbal
- Multidisciplinary Center for Advanced Research and Studies, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
- Correspondence: (Z.F.); (J.I.)
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20
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Cheng PN, Sun HY, Feng IC, Wang ST, Chiu YC, Chiu HC, Chien SC, Young KC. Post-therapeutic reversibility of oxidative-stress markers in chronic hepatitis C patients receiving direct-acting antiviral agents. J Virus Erad 2023; 9:100318. [PMID: 37065432 PMCID: PMC10091014 DOI: 10.1016/j.jve.2023.100318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 12/08/2022] [Accepted: 02/19/2023] [Indexed: 02/27/2023] Open
Abstract
Introduction Hepatitis C (HCV) is associated with extra-hepatic involvment, morbidity as well as metabolic changes. Whether these might be reversible if sustained virologic response (SVR) is achieved by direct-acting antiviral (DAA) therapy remains unknown. Methods Chronic hepatitis C (CHC) individuals receiving DAA treatment with SVR were compared to those who underwent spontaneous clearance (SC) of HCV infection at the 2-year follow-up. Plasma oxidative stress markers (oxidized low-density lipoprotein (oxLDL), 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA) and ischemia-modified albumin (IMA)) as well as progression of liver fibrosis were evaluated. Results Compared to SC individuals, those in the CHC group exhibited at baseline higher levels of oxLDL, 8-OHdG and IMA but not of MDA. In the SC group, 8-OHdG levels were elevated at 2-year post-SVR (p = 0.0409), while the DAA-treated CHC group showed decrease in oxLDL (p < 0.0001) and 8-OHdG (p = 0.0255) levels, approaching those of the SC group, but increased MDA (p = 0.0055) levels. Additionally, oxLDL levels were positively correlated with liver stiffness measurements at SVR (p = 0.017) and at 1 year post- SVR (p = 0.002). Conclusions Plasma oxLDL showed post-SVR normalization after clearance of HCV viremia with DAAs and was associated with levels of hepatic fibrosis.
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Affiliation(s)
- Pin-Nan Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hung-Yu Sun
- Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - I-Che Feng
- Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan
| | - Sin-Tian Wang
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yen-Cheng Chiu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hung-Chih Chiu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Shih-Chieh Chien
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Kung-Chia Young
- Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Corresponding author. Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, No. 1 University Rd, Tainan, 70101, Taiwan.
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Cheng PN, Sun HY, Feng IC, Chiu YC, Wang ST, Tan DC, Chiu HC, Chien SC, Young KC. Interdependence of glycemic and lipid modulation in cured chronic hepatitis C patients by direct-acting antiviral agents. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2023; 56:20-30. [PMID: 35842406 DOI: 10.1016/j.jmii.2022.06.004] [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: 11/06/2021] [Revised: 05/01/2022] [Accepted: 06/16/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND Chronic hepatitis C virus (HCV) infection causes various liver diseases and metabolic disorders. With direct-acting antiviral agents (DAAs), which effectively eradicate pan-genotypic HCV, hepatic and concomitant metabolic restorations are achieved. The study aims to evaluate the posttherapeutic benefits of lipid and glycemic homeostasis. METHODS Nighty-five chronic hepatitis C patients who achieved sustained virological response (SVR) by using DAAs were enrolled to collect plasma samples and fractionated lipoproteins at baseline, SVR, and during the post-SVR follow-ups for 6 months (pS6m) and 1 year (pS1yr). The lipid and glycemic parameters were analyzed to establish muturally modulatory relationships. RESULTS Plasma cholesterol (Chol) and glucose were elevated at SVR from baseline, whereas plasma Chol remained increased until pS1yr; however, glucose returned to the basal level. The post-SVR responses included a peak elevation of glycated hemoglobin at pS6m, a sustained elevation of triglyceride (Tg), and sustained declines in insulin, homeostasis model assessment (HOMA)-insulin resistance, and HOMA-beta levels until pS1yr. The changes in plasma Chol and high-density-lipoprotein Chol showed positive correlations, as did the plasma Tg with low-density-lipoprotein Tg and very-low-density-lipoprotein Tg per particle load. Very-low-density-lipoprotein was found to be loaded with increased Tg and Chol and underwent efficient Tg catabolism in the form of conversion into low-density-lipoprotein. Additionally, the posttherapeutic dynamics exhibited correlations of high-density-lipoprotein Chol with plasma glucose and HOMA-beta. CONCLUSION Irrespective of the baseline metabolic status, the posttherapeutic interdependent modulation of blood glycemic and lipid metabolic parameters were revealed in chronic hepatitis C patients following clearance of HCV viremia by DAA treatment.
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Affiliation(s)
- Pin-Nan Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hung-Yu Sun
- Department of Biomedical Engineering, College of Biology, Hunan University, Changsha, China; Institute of Pathogen Biology and Immunology of College of Biology, Hunan Provincial Key Laboratory of Medical Virology, Hunan University, Changsha, China; Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - I-Che Feng
- Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan
| | - Yen-Cheng Chiu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Sin-Tian Wang
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Dyoness Charmaine Tan
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hung-Chih Chiu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Shih-Chih Chien
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Kung-Chia Young
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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Hepatitis C Virus-Lipid Interplay: Pathogenesis and Clinical Impact. Biomedicines 2023; 11:biomedicines11020271. [PMID: 36830808 PMCID: PMC9953247 DOI: 10.3390/biomedicines11020271] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 01/13/2023] [Accepted: 01/16/2023] [Indexed: 01/20/2023] Open
Abstract
Hepatitis C virus (HCV) infection represents the major cause of chronic liver disease, leading to a wide range of hepatic diseases, including cirrhosis and hepatocellular carcinoma. It is the leading indication for liver transplantation worldwide. In addition, there is a growing body of evidence concerning the role of HCV in extrahepatic manifestations, including immune-related disorders and metabolic abnormalities, such as insulin resistance and steatosis. HCV depends on its host cells to propagate successfully, and every aspect of the HCV life cycle is closely related to human lipid metabolism. The virus circulates as a lipid-rich particle, entering the hepatocyte via lipoprotein cell receptors. It has also been shown to upregulate lipid biosynthesis and impair lipid degradation, resulting in significant intracellular lipid accumulation (steatosis) and circulating hypocholesterolemia. Patients with chronic HCV are at increased risk for hepatic steatosis, dyslipidemia, and cardiovascular disease, including accelerated atherosclerosis. This review aims to describe different aspects of the HCV viral life cycle as it impacts host lipoproteins and lipid metabolism. It then discusses the mechanisms of HCV-related hepatic steatosis, hypocholesterolemia, and accelerated atherosclerosis.
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23
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Tao J, Yan Z, Huang W, Feng T. Seropositive for hepatitis B and C viruses is associated with the risk of decreased bone mineral density in adults: An analysis of studies from the NHANES database. Front Med (Lausanne) 2023; 10:1120083. [PMID: 37035336 PMCID: PMC10073499 DOI: 10.3389/fmed.2023.1120083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 02/24/2023] [Indexed: 04/11/2023] Open
Abstract
Background Some studies had reported that patients with viral hepatitis are at increased risk of reduced bone mineral density and even osteoporosis. However, the interaction between reduced bone mineral density (BMD) and viral hepatitis remains inconclusive. Therefore, our study collected hepatitis test results and bone mineral density from respondents in the NHANES database. The aim of this study was to investigate whether there is an association between hepatitis and a decrease in bone mineral density. Methods The respondents with both hepatitis- and BMD-related indicators from the NHANES database in the United States from 2005-2010, 2013-2014, to 2017-2020 were collected for this study. BMD were compared between respondents who were positive and negative for respondents related to hepatitis B and C. BMD was measured using dual-energy X-ray absorptiometry of the femur and lumbar spine. Finally, multiple regression analysis was performed between hepatitis B surface antigen (HBsAg) and hepatitis C RNA (HCV-RNA) and BMD in the respondents. Results A total of 15,642 respondents were included in the hepatitis B surface antigen-related survey. Of these, 1,217 respondents were positive for hepatitis B surface antigen. A total of 5111 hepatitis C RNA-related responders were included. Hepatitis C RNA-positive had 268 respondents. According to the results of the multiple regression analysis, the femoral BMD was significantly lower in HBsAg (+) respondents compared to HBsAg (-) respondents: -0.018 (-0.026, -0.009) (P < 0.01). Moreover, spinal BMD was significantly lower in HBsAg (+) respondents compared to HBsAg (-) respondents: -0.020 (-0.030, -0.010) (P < 0.01). According to the results of multiple regression analysis for hepatitis C RNA, HCV-RNA (+) respondents had significantly lower BMD compared to HCV-RNA (-) respondents: -0.043 (-0.059, -0.026) (P < 0.01). Conclusion During the analysis of respondents in the NHANES database in the United States, positive tests for hepatitis B surface antigen and hepatitis C RNA were found to be associated with a reduction in BMD. Positive serology for these hepatitis indicators may increase the risk of reduced BMD. Of course, this conclusion still needs to be further confirmed by more large clinical trials.
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Affiliation(s)
- Jiasheng Tao
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
| | - Zijian Yan
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
| | - Wenmian Huang
- Affiliated Stomatological Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, China
| | - Tao Feng
- Department of Orthopedics, Nantong Hospital of Traditional Chinese Medicine, Nantong, Jiangsu, China
- *Correspondence: Tao Feng
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Zhang L, Wang X, Ming A, Tan W. Pseudotyped Virus for Flaviviridae. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1407:313-327. [PMID: 36920705 DOI: 10.1007/978-981-99-0113-5_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
Abstract
Members of Flaviviridae are enveloped single positive-stranded RNA viruses including hepacivirus, pestivirus, pegivirus, and mosquito-transmitted flavivirus, which are important pathogens of infectious diseases and pose serious threats to human health. Pseudotyped virus is an artificially constructed virus-like particle, which could infect host cells similar to a live virus but cannot produce infectious progeny virus. Therefore, pseudotyped virus has the advantages of a wide host range, high transfection efficiency, low biosafety risk, and accurate and objective quantification. It has been widely used in biological characteristics, drug screening, detection methods, and vaccine evaluation of Flaviviridae viruses like hepatitis C virus, Japanese encephalitis virus, dengue virus, and Zika virus.
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Affiliation(s)
- Leiliang Zhang
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Department of Pathogen Biology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Xiao Wang
- Department of Pathogen Biology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Annan Ming
- Department of Pathogen Biology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Wenjie Tan
- NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
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Weigand K, Peschel G, Grimm J, Müller M, Höring M, Krautbauer S, Liebisch G, Buechler C. HCV Infection and Liver Cirrhosis Are Associated with a Less-Favorable Serum Cholesteryl Ester Profile Which Improves through the Successful Treatment of HCV. Biomedicines 2022; 10:biomedicines10123152. [PMID: 36551908 PMCID: PMC9775323 DOI: 10.3390/biomedicines10123152] [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: 10/31/2022] [Revised: 11/28/2022] [Accepted: 12/03/2022] [Indexed: 12/12/2022] Open
Abstract
Background: Infection with hepatitis C virus (HCV) lowers serum cholesterol levels, which rapidly recover during therapy with direct-acting antivirals (DAAs). Serum cholesterol is also reduced in patients with liver cirrhosis. Studies investigating serum cholesterol in patients with chronic liver diseases are generally based on enzymatic assays providing total cholesterol levels. Hence, these studies do not account for the individual cholesteryl ester (CE) species, which have different properties according to acyl chain length and desaturation. Methods: Free cholesterol (FC) and 15 CE species were quantified by flow injection analysis high-resolution Fourier Transform mass spectrometry (FIA-FTMS) in the serum of 178 patients with chronic HCV before therapy and during treatment with DAAs. Results: Serum CEs were low in HCV patients with liver cirrhosis and, compared to patients without cirrhosis, proportions of CE 16:0 and 16:1 were higher whereas % CE 20:4 and 20:5 were reduced. FC levels were unchanged, and the CE/FC ratio was consequently low in cirrhosis. FC and CEs did not correlate with viral load. Four CE species were reduced in genotype 3 compared to genotype 1-infected patients. During DAA therapy, 9 of the 15 measured CE species, and the CE/FC ratio, increased. Relative to total CE levels, % CE 16:0 declined and % CE 18:3 was higher at therapy end. At this time, % CE 14:0, 16:0 and 16:1 were higher and % CE 20:4 and 22:6 were lower in the cirrhosis than the non-cirrhosis patients. Viral genotype associated changes of CEs disappeared at therapy end. Conclusions: The serum CE composition differs between patients with and without liver cirrhosis, and changes through the efficient elimination of HCV. Overall, HCV infection and cirrhosis are associated with a higher proportion of CE species with a lower number of carbon atoms and double bonds, reflecting a less-favorable CE profile.
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Affiliation(s)
- Kilian Weigand
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany
- Department of Gastroenterology, Gemeinschaftsklinikum Mittelrhein, 56073 Koblenz, Germany
| | - Georg Peschel
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany
- Department of Internal Medicine, Klinikum Fürstenfeldbruck, 82256 Fürstenfeldbruck, Germany
| | - Jonathan Grimm
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Martina Müller
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Marcus Höring
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Sabrina Krautbauer
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Gerhard Liebisch
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Christa Buechler
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany
- Correspondence: ; Tel.: +49-941-944-7009
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Barré T, Carrat F, Ramier C, Fontaine H, Di Beo V, Bureau M, Dorival C, Larrey D, Delarocque-Astagneau E, Mathurin P, Marcellin F, Petrov-Sanchez V, Cagnot C, Carrieri P, Pol S, Protopopescu C, Alric L, Pomes C, Zoulim F, Maynard M, Bai R, Hucault L, Bailly F, Raffi F, Billaud E, Boutoille D, Lefebvre M, André-Garnier E, Cales P, Hubert I, Lannes A, Lunel F, Boursier J, Asselah T, Boyer N, Giuily N, Castelnau C, Scoazec G, Pol S, Fontaine H, Rousseaud E, Vallet-Pichard A, Sogni P, de Ledinghen V, Foucher J, Hiriart JB, M’Bouyou J, Irlès-Depé M, Bourlière M, Ahmed SNS, Oules V, Tran A, Anty R, Gelsi E, Truchi R, Thabut D, Hammeche S, Moussali J, Causse X, De Dieuleveult B, Ouarani B, Labarrière D, Ganne N, Grando-Lemaire V, Nahon P, Brulé S, Ulker B, Guyader D, Jezequel C, Brener A, Laligant A, Rabot A, Renard I, Habersetzer F, Baumert TF, Doffoel M, Mutter C, Simo-Noumbissie P, Razi E, Bronowicki JP, Barraud H, Bensenane M, Nani A, Hassani-Nani S, Bernard MA, Pageaux GP, Larrey D, Meszaros M, Metivier S, Bureau C, Morales T, Peron JM, Robic MA, Decaens T, Faure M, Froissart B, Hilleret MN, Zarski JP, Riachi G, Goria O, et alBarré T, Carrat F, Ramier C, Fontaine H, Di Beo V, Bureau M, Dorival C, Larrey D, Delarocque-Astagneau E, Mathurin P, Marcellin F, Petrov-Sanchez V, Cagnot C, Carrieri P, Pol S, Protopopescu C, Alric L, Pomes C, Zoulim F, Maynard M, Bai R, Hucault L, Bailly F, Raffi F, Billaud E, Boutoille D, Lefebvre M, André-Garnier E, Cales P, Hubert I, Lannes A, Lunel F, Boursier J, Asselah T, Boyer N, Giuily N, Castelnau C, Scoazec G, Pol S, Fontaine H, Rousseaud E, Vallet-Pichard A, Sogni P, de Ledinghen V, Foucher J, Hiriart JB, M’Bouyou J, Irlès-Depé M, Bourlière M, Ahmed SNS, Oules V, Tran A, Anty R, Gelsi E, Truchi R, Thabut D, Hammeche S, Moussali J, Causse X, De Dieuleveult B, Ouarani B, Labarrière D, Ganne N, Grando-Lemaire V, Nahon P, Brulé S, Ulker B, Guyader D, Jezequel C, Brener A, Laligant A, Rabot A, Renard I, Habersetzer F, Baumert TF, Doffoel M, Mutter C, Simo-Noumbissie P, Razi E, Bronowicki JP, Barraud H, Bensenane M, Nani A, Hassani-Nani S, Bernard MA, Pageaux GP, Larrey D, Meszaros M, Metivier S, Bureau C, Morales T, Peron JM, Robic MA, Decaens T, Faure M, Froissart B, Hilleret MN, Zarski JP, Riachi G, Goria O, Paris F, Montialoux H, Leroy V, Amaddeo G, Varaut A, Simoes M, Amzal R, Chazouillières O, Andreani T, Angoulevant B, Chevance A, Serfaty L, Samuel D, Antonini T, Coilly A, Duclos-Vallée JC, Tateo M, Abergel A, Reymond M, Brigitte C, Benjamin B, Muti L, Geist C, Conroy G, Riffault R, Rosa I, Barrault C, Costes L, Hagège H, Loustaud-Ratti V, Carrier P, Debette-Gratien M, Mathurin P, Lassailly G, Lemaitre E, Canva V, Dharancy S, Louvet A, Minello A, Latournerie M, Bardou M, Mouillot T, D’Alteroche L, Barbereau D, Nicolas C, Elkrief L, Jaillais A, Gournay J, Chevalier C, Archambeaud I, Habes S, Portal I, Gelu-Simeon M, Saillard E, Lafrance MJ, Catherine L, Carrat F, Chau F, Dorival C, Goderel I, Lusivika-Nzinga C, Bellance MA, Bellet J, Monfalet P, Chane-Teng J, Bijaoui S, Pannetier G, Téoulé F, Nicol J, Sebal F, Bekhti R, Cagnot C, Boston A, Nailler L, Le Meut G, Diallo A, Petrov-Sanchez V, Bourlière M, Boursier J, Carrat F, Carrieri P, Delarocque-Astagneau E, De Ledinghen V, Dorival C, Fontaine H, Fourati S, Housset C, Larrey D, Nahon P, Pageaux GP, Petrov-Sanchez V, Pol S, Bruyand M, Wittkop L, Zoulim F, Zucman-Rossi J, L’hennaff M, Sizorn M, Cagnot C, the ANRS/AFEF Hepather study group. Cannabis use as a factor of lower corpulence in hepatitis C-infected patients: results from the ANRS CO22 Hepather cohort. J Cannabis Res 2022; 4:31. [PMID: 35690798 PMCID: PMC9188079 DOI: 10.1186/s42238-022-00138-9] [Show More Authors] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 05/19/2022] [Indexed: 11/21/2022] Open
Abstract
Background Patients with chronic hepatitis C virus (HCV) infection are at greater risk of developing metabolic disorders. Obesity is a major risk factor for these disorders, and therefore, managing body weight is crucial. Cannabis use, which is common in these patients, has been associated with lower corpulence in various populations. However, this relationship has not yet been studied in persons with chronic HCV infection. Methods Using baseline data from the French ANRS CO22 Hepather cohort, we used binary logistic and multinomial logistic regression models to test for an inverse relationship between cannabis use (former/current) and (i) central obesity (i.e., large waist circumference) and (ii) overweight and obesity (i.e., elevated body mass index (BMI)) in patients from the cohort who had chronic HCV infection. We also tested for relationships between cannabis use and both waist circumference and BMI as continuous variables, using linear regression models. Results Among the 6348 participants in the study population, 55% had central obesity, 13.7% had obesity according to their BMI, and 12.4% were current cannabis users. After multivariable adjustment, current cannabis use was associated with lower risk of central obesity (adjusted odds ratio, aOR [95% confidence interval, CI]: 0.45 [0.37–0.55]), BMI-based obesity (adjusted relative risk ratio (aRRR) [95% CI]: 0.27 [0.19–0.39]), and overweight (aRRR [95% CI]: 0.47 [0.38–0.59]). This was also true for former use, but to a lesser extent. Former and current cannabis use were inversely associated with waist circumference and BMI. Conclusions We found that former and, to a greater extent, current cannabis use were consistently associated with smaller waist circumference, lower BMI, and lower risks of overweight, obesity, and central obesity in patients with chronic HCV infection. Longitudinal studies are needed to confirm these relationships and to assess the effect of cannabis use on corpulence and liver outcomes after HCV cure. Trial registration ClinicalTrials.gov identifier: NCT01953458.
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Lowe R, Hey P, Sinclair M. The sex-specific prognostic utility of sarcopenia in cirrhosis. J Cachexia Sarcopenia Muscle 2022; 13:2608-2615. [PMID: 35945660 PMCID: PMC9745556 DOI: 10.1002/jcsm.13059] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 06/07/2022] [Accepted: 07/04/2022] [Indexed: 12/15/2022] Open
Abstract
Sarcopenia is an increasingly recognized complication of cirrhosis that is associated with morbidity and mortality. Differences in the prevalence and prognosis of sarcopenia between men and women have been reported in other patient groups, but there is insufficient understanding of how sex impacts the prognostic value of sarcopenia in cirrhosis. A search of MEDLINE and Embase was conducted from earliest entries to April 2021. Studies were included if they examined sex-stratified mortality impact of reduced muscle function or mass in outpatient populations with cirrhosis. We identified 700 studies of which 6 were deemed relevant for inclusion in this narrative review. Studies of interest were heterogeneous, precluding pooling of data and making interpretation of the literature challenging. Muscle mass was assessed in five studies (n = 2566, 1730 men, 836 women) and was reduced in 36-50% of men and 24-43% of women. All five studies found that reduced muscle mass determined by computed tomography, dual-energy X-ray absorptiometry, and bioelectrical impedance analysis was associated with increased mortality in men. Of these, two studies identified a corresponding relationship in women; reduced muscle mass defined by computed tomography was associated with increased mortality [hazard ratio (HR) 2.82, P = 0.001], while increasing muscle mass by bioelectrical impedance analysis likewise conferred a survival benefit (HR 0.45, P = 0.0016). Only one study assessed the relationship of muscle function with sex-stratified mortality (n = 1405, 827 men, 578 women), concluding that reduced muscle function predicted mortality in both men and women (HR 1.65, P < 0.001 and HR 1.54, P < 0.001, respectively). Reduced muscle mass in cirrhosis is consistently associated with mortality in men, but lack of sex-stratification of mortality analyses limits the ability to make strong conclusions about the impact of sarcopenia specifically in women, with even fewer data available for analysing muscle function. Improved understanding of the sex-specific impacts of sarcopenia may help address patient deterioration and mortality while awaiting liver transplantation and allow for early intervention to mitigate mortality risk. Large, multicentre studies with adequate female participation and sex-stratified mortality analyses are warranted.
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Affiliation(s)
- Ryan Lowe
- University of MelbourneMelbourneVictoriaAustralia
- Northern HealthEppingVictoriaAustralia
| | - Penelope Hey
- University of MelbourneMelbourneVictoriaAustralia
- Liver Transplant UnitAustin HealthHeidelbergVictoriaAustralia
| | - Marie Sinclair
- University of MelbourneMelbourneVictoriaAustralia
- Liver Transplant UnitAustin HealthHeidelbergVictoriaAustralia
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28
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Chua D, Low ZS, Cheam GX, Ng AS, Tan NS. Utility of Human Relevant Preclinical Animal Models in Navigating NAFLD to MAFLD Paradigm. Int J Mol Sci 2022; 23:14762. [PMID: 36499091 PMCID: PMC9737809 DOI: 10.3390/ijms232314762] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 11/15/2022] [Accepted: 11/23/2022] [Indexed: 11/29/2022] Open
Abstract
Fatty liver disease is an emerging contributor to disease burden worldwide. The past decades of work established the heterogeneous nature of non-alcoholic fatty liver disease (NAFLD) etiology and systemic contributions to the pathogenesis of the disease. This called for the proposal of a redefinition in 2020 to that of metabolic dysfunction-associated fatty liver disease (MAFLD) to better reflect the current understanding of the disease. To date, several clinical cohort studies comparing NAFLD and MAFLD hint at the relevancy of the new nomenclature in enriching for patients with more severe hepatic injury and extrahepatic comorbidities. However, the underlying systemic pathogenesis is still not fully understood. Preclinical animal models have been imperative in elucidating key biological mechanisms in various contexts, including intrahepatic disease progression, interorgan crosstalk and systemic dysregulation. Furthermore, they are integral in developing novel therapeutics against MAFLD. However, substantial contextual variabilities exist across different models due to the lack of standardization in several aspects. As such, it is crucial to understand the strengths and weaknesses of existing models to better align them to the human condition. In this review, we consolidate the implications arising from the change in nomenclature and summarize MAFLD pathogenesis. Subsequently, we provide an updated evaluation of existing MAFLD preclinical models in alignment with the new definitions and perspectives to improve their translational relevance.
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Affiliation(s)
- Damien Chua
- Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, 11 Mandalay Road, Singapore 308232, Singapore
| | - Zun Siong Low
- Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, 11 Mandalay Road, Singapore 308232, Singapore
| | - Guo Xiang Cheam
- School of Biological Sciences, Nanyang Technological University Singapore, 60 Nanyang Drive, Singapore 637551, Singapore
| | - Aik Seng Ng
- Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK
| | - Nguan Soon Tan
- Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, 11 Mandalay Road, Singapore 308232, Singapore
- School of Biological Sciences, Nanyang Technological University Singapore, 60 Nanyang Drive, Singapore 637551, Singapore
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Cardiovascular Risk Factors in Patients with Congenital Hemophilia: A Focus on Hypertension. Diagnostics (Basel) 2022; 12:diagnostics12122937. [PMID: 36552943 PMCID: PMC9776547 DOI: 10.3390/diagnostics12122937] [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: 10/31/2022] [Revised: 11/18/2022] [Accepted: 11/20/2022] [Indexed: 11/27/2022] Open
Abstract
Aging hemophiliacs face cardiovascular disease. Lots of evidence has been gathered that hemophiliacs have a more unfavorable cardiovascular profile than the general population does, especially due to the increased prevalence of hypertension (HTN). Among the existing scattered evidence, our study provides the most comprehensive and systematized analysis of the determinants of HTN in hemophiliacs. We discussed the contribution to the HTN substrate of hemophilia-specific factors, such as type, severity and the presence of inhibitors. The complex mechanism of kidney dysfunction in relation to hematuria and viral infections was meticulously addressed. Furthermore, we highlighted the new pathogenic concepts of endothelial dysfunction and the association between HTN and hemophilic arthropathy. The clustering of cardiovascular risk factors is common in hemophiliacs, and it enhances the negative vascular effect of HTN and aggravates HTN. It usually leads to an increased risk for coronary and cerebrovascular events. Our work provides reliable evidence to guide and improve the management of HTN in hemophiliacs.
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Chi ZC. Progress in understanding of association between metabolic associated fatty liver disease and viral infectious diseases. Shijie Huaren Xiaohua Zazhi 2022; 30:783-794. [DOI: 10.11569/wcjd.v30.i18.783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Metabolic associated fatty liver disease (MAFLD) is a chronic liver disease with the highest incidence in the world, which affects 1/4-1/3 of the world population and has a serious effect on people's health. As is a multi-systemic disease, MAFLD is closely related to the occurrence and prognosis of many diseases. Studies have shown that MAFLD is associated with viral infectious diseases, and their interaction affects the prognosis of the disease. This paper reviews the research progress in this field in recent years.
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Affiliation(s)
- Zhao-Chun Chi
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266011, Shandong Province, China
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31
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Choi GH, Jang ES, Kim YS, Lee YJ, Kim IH, Cho SB, Lee HC, Jang JW, Ki M, Choi HY, Baik D, Jeong SH. Hepatocellular carcinoma, decompensation, and mortality based on hepatitis C treatment: A prospective cohort study. World J Gastroenterol 2022; 28:4182-4200. [PMID: 36157119 PMCID: PMC9403421 DOI: 10.3748/wjg.v28.i30.4182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Revised: 04/24/2022] [Accepted: 07/16/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Prospective studies of the long-term outcomes of patients with hepatitis C virus (HCV) infection after treatment with interferon-based therapy (IBT) or direct-acting antivirals (DAA) are limited in many Asian countries. AIM To elucidate the incidences of hepatocellular carcinoma (HCC) and death/transplantation based on treatment with IBT or DAA, to compare the outcomes of the sustained virologic response (SVR) to IBT and DAA, and to investigate outcome-determining factors after SVR. METHODS This cohort included 2054 viremic patients (mean age, 57 years; 46.5% male; 27.4% with cirrhosis) prospectively enrolled at seven hospitals between 2007 and 2019. They were classified as the untreated group (n = 619), IBT group (n = 578), and DAA group (n = 857). Outcomes included the incidences of HCC and death/transplantation. The incidences of the outcomes for each group according to treatment were calculated using an exact method based on the Poisson distribution. A multivariate Cox regression analysis was performed to determine the factors associated with HCC or death/transplantation, followed by propensity score matching to confirm the results. RESULTS During a median of 4.1 years of follow-up, HCC and death/transplantation occurred in 113 and 206 patients, respectively, in the entire cohort. Compared with the untreated group, the incidences of HCC and death/transplantation were significantly lower in the IBT group [adjusted hazard ratio (aHR) 0.47, 95%CI: 0.28-0.80 and aHR 0.28, 95%CI: 0.18-0.43, respectively] and the DAA group (aHR 0.58, 95%CI: 0.35-0.96, and aHR 0.19, 95%CI: 0.20-0.68, respectively). Among 1268 patients who attained SVR with IBT (n = 451) or DAA (n = 816), the multivariable-adjusted analysis showed no differences in the risks of HCC (HR 2.03; 95%CI: 0.76-5.43) and death/transplantation (HR 1.38; 95%CI: 0.55-3.49) between the two groups. This was confirmed by a propensity score-matching analysis. Independent factors for HCC after SVR were age, genotype 1, and the presence of cirrhosis. CONCLUSION Treatment and achieving SVR with either IBT or DAA significantly reduced the incidences of HCC and mortality in the Asian patients with HCV infection. The risks of HCC and mortality were not significantly different regardless of whether SVR was induced by IBT or DAA.
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Affiliation(s)
- Gwang Hyeon Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, South Korea
| | - Eun Sun Jang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, South Korea
| | - Young Seok Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon 14584, South Korea
| | - Youn Jae Lee
- Department of Internal Medicine, Inje University Busan Paik Hospital, Busan 47392, South Korea
| | - In Hee Kim
- Department of Internal Medicine, Chonbuk National University Hospital, Jeonju 54907, Jeonbuk, South Korea
| | - Sung Bum Cho
- Department of Internal Medicine, Chonnam National University Hwasun Hospital, Hwasun 58128, South Korea
| | - Han Chu Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, South Korea
| | - Jeong Won Jang
- Department of Internal Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - Moran Ki
- Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, South Korea
| | - Hwa Young Choi
- Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, South Korea
| | - Dahye Baik
- Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, South Korea
| | - Sook-Hyang Jeong
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, South Korea
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El-Kassas M, Awad A. Metabolic aspects of hepatitis C virus. World J Gastroenterol 2022; 28:2429-2436. [PMID: 35979265 PMCID: PMC9258278 DOI: 10.3748/wjg.v28.i22.2429] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 03/18/2022] [Accepted: 04/22/2022] [Indexed: 02/06/2023] Open
Abstract
Many metabolic factors are associated with chronic hepatitis C virus (HCV) infection and can influence the course of the illness and impact the progression of liver and non-liver-related diseases through complex interactions. Several of these factors impact the course of chronic HCV (CHC) and result in the conceptual translation of CHC from a localized to systemic disease. Besides the traditional liver manifestations associated with CHC infection, such as cirrhosis and hepatocellular carcinoma, various extrahepatic disorders are associated with HCV infection, including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases. The coexistence of metabolic disorders and CHC is known to influence the chronicity and virulence of HCV and accelerates the progression to liver fibrosis and hepatocellular carcinoma. Insulin resistance is one of the key factors that have a tremendous metabolic impact on CHC. Therefore, there is a great need to properly evaluate patients with CHC infection and correct the modifiable metabolic risk factors. Furthermore, patients with HCV who achieved a sustained virological response showed an overall improvement in glucose metabolism, but the exact evidence still requires further studies with long-term follow-up. This review delineates the most recent evidence on the main metabolic factors associated with CHC and the possible influence of chronic HCV infection on metabolic features.
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Affiliation(s)
- Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo 11795, Egypt
| | - Abeer Awad
- Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 11566, Egypt
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Beliy PA, Dudina KR, Znoyko OO, Markova TN, Morozova IA, Blokhina NP, Nurmukhametova EA, Yushchuk ND. Prevalence of chronic HCV infection in patients with type 2 diabetes mellitus in Russia. DIABETES MELLITUS 2022; 25:4-13. [DOI: 10.14341/dm12847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
BACKGROUND: The poor outcomes of chronic hepatitis C (CHC) and type 2 diabetes determine the socio-economic significance of the combined pathology since they lead to premature death. The proportion of patients with type 2 diabetes with markers of viral hepatitis (VH) in the Russian Federation is not known, which does not allow us to estimate the burden for the state of this medical problem.OBJECTIVE: Assessment of the prevalence of concomitant pathology, HCV infection and type 2 diabetes, as well as the proportion of severe liver damage in its structure, according to the analysis of the primary medical records of four Moscow hospitals.MATERIALS AND METHODS: A retrospective analysis of the medical records of patients with HCV infection and diabetes mellitus, who admitted at different periods to four hospitals in Moscow, was carried out, as well as a total examination for the presence of anti-HCV in the blood of all patients with diabetes who were admitted within a certain period to the endocrinology department of a multidisciplinary hospital. Additionally, to determine the proportion of patients with liver cirrhosis (LC), an additional examination of patients with this combined pathology was carried out in accordance with the standards for the diagnosis of hepatitis C.RESULTS: In total, according to data from 4 hospitals in Moscow, over a certain period, 2% (105/5298) of diabetes patients with anti-HCV in their blood were identified. Sex ratio for men: women = 54 (51%): 51 (49%). Patients aged 50–69 years prevailed — 70% (74/105). Seroprevalence of HCV in cohorts of patients with type 2 diabetes according to the analysis in 3 health facilities: 0.9% (20/2196), 1.9% (8/432), 1.9% (28/1500). A significant drawback was revealed that did not allow assessing the true seroprevalence of HCV: not all patients were hospitalized with the results of a VH test, and not all of them were assigned an examination for VH markers if it was not performed before hospitalization. The proportion of type 2 diabetes patients with anti-HCV in the blood according to the results of total screening (3.7%; 16/432) became comparable to the proportion of type 2 diabetes patients among patients with CHC admitted to an infectious hospital (4.2%; 49 / 1170). The proportion of patients with LC according to the analysis of the medical records of the infectious hospital is 65% (32/49), in the group of endocrinological patients with additional examination it is 18% (13/71).CONCLUSION: For the first time in the Russian Federation, data were obtained on the prevalence of HCV infection in combination with type 2 diabetes. The results of the study indicate the need to develop effective screening programs to detect active HCV infection in the group of patients with diabetes, as well as patients among them with severe hepatic fibrosis for the timely conduct of highly effective antiviral therapy, which will prevent poor outcomes in a separate perspective.
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Affiliation(s)
- P. A. Beliy
- A.I. Evdokimov Moscow State University of Medicine and Dentistry
| | - K. R. Dudina
- A.I. Evdokimov Moscow State University of Medicine and Dentistry
| | - O. O. Znoyko
- A.I. Evdokimov Moscow State University of Medicine and Dentistry
| | | | | | | | | | - N. D. Yushchuk
- A.I. Evdokimov Moscow State University of Medicine and Dentistry
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Wang PC, Wu YF, Lin MS, Lin CL, Chang ML, Chang ST, Weng TC, Chen MY. The Impact of Hepatitis C Virus, Metabolic Disturbance, and Unhealthy Behavior on Chronic Kidney Disease: A Secondary Cross-Sectional Analysis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:3558. [PMID: 35329244 PMCID: PMC8952695 DOI: 10.3390/ijerph19063558] [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: 01/21/2022] [Revised: 03/09/2022] [Accepted: 03/11/2022] [Indexed: 11/17/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is associated with a higher risk of chronic kidney disease (CKD). This study investigates the relationship among HCV, CKD, and understudied confounders, such as unhealthy behaviors and metabolic disturbances. METHODS This cross-sectional study was conducted as part of a community health promotion program in an HCV endemic area of Taiwan from June to December 2019. Multivariable logistic regression analyses adjusted for demographic and clinical characteristics were performed to investigate the association between CKD and HCV seropositivity. RESULTS Of 2387 participants who underwent health check-ups, the mean age was 64.1 years old; females predominated (63.2%), and 306 (12.8%) subjects were seropositive for HCV. CKD, defined as a lower estimated glomerular filtration rate (eGFR) was associated with unhealthy dietary habits, metabolic syndrome, and HCV. Less frequent exercise, higher waist circumference (WC) and HbA1c all affected risk of CKD; HCV increased risk of CKD by 44% compared to non-HCV (OR 1.44, 95% confidence interval (CI) 1.05-1.98) in the multivariable analysis. In the HCV group, lower eGFR was also significantly associated with the severity of metabolic syndrome (MetS) (median eGFR was 86.4, 77.1, and 64.5 mL/min/1.73 m2 for individuals with three and five MetS components, respectively). CONCLUSIONS Beyond metabolic disturbance and irregular exercise, HCV seropositivity is independently associated with CKD in a community survey. Healthy lifestyle promotion might protect against renal function decline in HCV; however, the mechanisms underlying the association need further large-scale investigation.
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Affiliation(s)
- Po-Chang Wang
- Division of Internal Medicine, Department of Cardiology, Chang Gung Memorial Hospital, Chiayi 613, Taiwan; (P.-C.W.); (M.-S.L.); (S.-T.C.); (T.-C.W.)
| | - Yi-Fang Wu
- Department of Emergency Medicine, Chang Gung Memorial Hospital, Chiayi 613, Taiwan;
| | - Ming-Shyan Lin
- Division of Internal Medicine, Department of Cardiology, Chang Gung Memorial Hospital, Chiayi 613, Taiwan; (P.-C.W.); (M.-S.L.); (S.-T.C.); (T.-C.W.)
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Chun-Liang Lin
- Department of Nephrology, Chang Gung Memorial Hospital, Chiayi 613, Taiwan;
- Kidney Research Center, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
- College of Medicine, Chang Gung University, Taiyuan 333, Taiwan;
| | - Ming-Ling Chang
- College of Medicine, Chang Gung University, Taiyuan 333, Taiwan;
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Shih-Tai Chang
- Division of Internal Medicine, Department of Cardiology, Chang Gung Memorial Hospital, Chiayi 613, Taiwan; (P.-C.W.); (M.-S.L.); (S.-T.C.); (T.-C.W.)
- College of Medicine, Chang Gung University, Taiyuan 333, Taiwan;
| | - Tzu-Chieh Weng
- Division of Internal Medicine, Department of Cardiology, Chang Gung Memorial Hospital, Chiayi 613, Taiwan; (P.-C.W.); (M.-S.L.); (S.-T.C.); (T.-C.W.)
| | - Mei-Yen Chen
- Division of Internal Medicine, Department of Cardiology, Chang Gung Memorial Hospital, Chiayi 613, Taiwan; (P.-C.W.); (M.-S.L.); (S.-T.C.); (T.-C.W.)
- Department of Nursing, Chang Gung University of Science and Technology, Chiayi 613, Taiwan
- School of Nursing, Chang Gung University, Taoyuan 333, Taiwan
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Prata TVG, Manchiero C, Dantas BP, Nunes AKDS, Tengan FM, Magri MC. Effect of MTTP -493G/T, I128T, Q95H and Q244E polymorphisms on hepatic steatosis in patients with chronic hepatitis. Clinics (Sao Paulo) 2022; 77:100094. [PMID: 36027755 PMCID: PMC9424342 DOI: 10.1016/j.clinsp.2022.100094] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 06/21/2022] [Accepted: 07/12/2022] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Chronic hepatitis C is characterized by a progressive deterioration of liver function and is involved in metabolic complications, such as hepatic steatosis. OBJECTIVE The aim of this study was to investigate the role of host and viral characteristics associated with -493G/T (rs1800591), I128T (rs3816873), Q95H (rs61733139), and Q244E (rs17599091) Single Nucleotide Polymorphisms (SNPs) in the Microsomal Triglyceride Transfer Protein (MTTP) gene on hepatic steatosis in chronic hepatitis C. METHODS SNPs were genotyped by PCR-RFLP and analyzed in combination with host and viral characteristics by multiple logistic regression in different genetic models of inheritance. RESULTS The authors analyzed 236 patients with chronic hepatitis C, and 53% had hepatic steatosis. The mutated allele frequencies were > 5%, and the genotypes were in Hardy-Weinberg equilibrium (p ≥ 0.05). It was observed that patients with HCV genotype 3 infection (OR = 2.74, 95% CI 1.24‒6.06, p = 0.013), female sex (OR = 2.28, 95% CI 1.21‒4.28, p = 0.011) and moderate- and high-intensity liver inflammatory activity (A2-A3) (OR = 3.61, 95% CI 1.86‒7.01, p < 0.001) alone exhibited a higher risk of steatosis. The results of multiple logistic regression analysis for interaction showed that for the -493G/T SNP, when the GT/TT genotype (dominant model) and the GT genotype (codominant model) were each combined with HCV genotype 3 infection, an 11.51-fold (95% CI 2.08‒63.59, p = 0.005) and a 15.69-fold (95% CI 2.46‒99.85, p = 0.004) increased risk of steatosis, respectively, was observed. For the I128T SNP, when both the IT/TT genotype (dominant model) and the IT genotype (codominant model) were combined with HCV genotype 3 infection, an 8.51-fold (95% CI 1.59‒45.54, p = 0.012) and an 8.40 fold (95% CI 1.51‒46.91, p = 0.015) increased risk of steatosis, respectively, was observed. CONCLUSION The present study showed that the viral genotype combined with the -493G/T and I128T SNPs in the MTTP gene influences hepatic steatosis.
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Affiliation(s)
- Thamiris Vaz Gago Prata
- Laboratorio de Investigacao Médica em Hepatologia por Virus (LIM-47), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Caroline Manchiero
- Laboratorio de Investigacao Médica em Hepatologia por Virus (LIM-47), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Bianca Peixoto Dantas
- Laboratorio de Investigacao Médica em Hepatologia por Virus (LIM-47), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Arielle Karen da Silva Nunes
- Laboratorio de Investigacao Médica em Hepatologia por Virus (LIM-47), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Fátima Mitiko Tengan
- Laboratorio de Investigacao Médica em Hepatologia por Virus (LIM-47), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil; Departamento de Molestias Infecciosas e Parasitarias, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil
| | - Mariana Cavalheiro Magri
- Laboratorio de Investigacao Médica em Hepatologia por Virus (LIM-47), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil.
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Krapić M, Kavazović I, Wensveen FM. Immunological Mechanisms of Sickness Behavior in Viral Infection. Viruses 2021; 13:v13112245. [PMID: 34835051 PMCID: PMC8624889 DOI: 10.3390/v13112245] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 11/04/2021] [Indexed: 12/11/2022] Open
Abstract
Sickness behavior is the common denominator for a plethora of changes in normal behavioral routines and systemic metabolism during an infection. Typical symptoms include temperature, muscle weakness, and loss of appetite. Whereas we experience these changes as a pathology, in fact they are a carefully orchestrated response mediated by the immune system. Its purpose is to optimize immune cell functionality against pathogens whilst minimizing viral replication in infected cells. Sickness behavior is controlled at several levels, most notably by the central nervous system, but also by other organs that mediate systemic homeostasis, such as the liver and adipose tissue. Nevertheless, the changes mediated by these organs are ultimately initiated by immune cells, usually through local or systemic secretion of cytokines. The nature of infection determines which cytokine profile is induced by immune cells and therefore which sickness behavior ensues. In context of infection, sickness behavior is typically beneficial. However, inappropriate activation of the immune system may induce adverse aspects of sickness behavior. For example, tissue stress caused by obesity may result in chronic activation of the immune system, leading to lasting changes in systemic metabolism. Concurrently, metabolic disease prevents induction of appropriate sickness behavior following viral infection, thus impairing the normal immune response. In this article, we will revisit recent literature that elucidates both the benefits and the negative aspects of sickness behavior in context of viral infection.
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Echeverría N, Comas V, Aldunate F, Perbolianachis P, Moreno P, Cristina J. In the era of rapid mRNA-based vaccines: Why is there no effective hepatitis C virus vaccine yet? World J Hepatol 2021; 13:1234-1268. [PMID: 34786164 PMCID: PMC8568586 DOI: 10.4254/wjh.v13.i10.1234] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 05/14/2021] [Accepted: 09/10/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) is responsible for no less than 71 million people chronically infected and is one of the most frequent indications for liver transplantation worldwide. Despite direct-acting antiviral therapies fuel optimism in controlling HCV infections, there are several obstacles regarding treatment accessibility and reinfection continues to remain a possibility. Indeed, the majority of new HCV infections in developed countries occur in people who inject drugs and are more plausible to get reinfected. To achieve global epidemic control of this virus the development of an effective prophylactic or therapeutic vaccine becomes a must. The coronavirus disease 19 (COVID-19) pandemic led to auspicious vaccine development against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus, which has renewed interest on fighting HCV epidemic with vaccination. The aim of this review is to highlight the current situation of HCV vaccine candidates designed to prevent and/or to reduce HCV infectious cases and their complications. We will emphasize on some of the crossroads encountered during vaccine development against this insidious virus, together with some key aspects of HCV immunology which have, so far, hampered the progress in this area. The main focus will be on nucleic acid-based as well as recombinant viral vector-based vaccine candidates as the most novel vaccine approaches, some of which have been recently and successfully employed for SARS-CoV-2 vaccines. Finally, some ideas will be presented on which methods to explore for the design of live-attenuated vaccines against HCV.
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Affiliation(s)
- Natalia Echeverría
- Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo 11400, Uruguay
| | - Victoria Comas
- Departamento de Desarrollo Biotecnológico, Instituto de Higiene, Facultad de Medicina, Universidad de la República, Montevideo 11600, Uruguay
| | - Fabián Aldunate
- Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo 11400, Uruguay
| | - Paula Perbolianachis
- Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo 11400, Uruguay
| | - Pilar Moreno
- Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo 11400, Uruguay
| | - Juan Cristina
- Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo 11400, Uruguay.
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Siphepho PY, Liu YT, Shabangu CS, Huang JF, Huang CF, Yeh ML, Yu ML, Wang SC. The Impact of Steatosis on Chronic Hepatitis C Progression and Response to Antiviral Treatments. Biomedicines 2021; 9:1491. [PMID: 34680608 PMCID: PMC8533513 DOI: 10.3390/biomedicines9101491] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 10/12/2021] [Accepted: 10/13/2021] [Indexed: 02/07/2023] Open
Abstract
Metabolic derangement is characteristic in patients with hepatitis C virus (HCV) infection. Aside from established liver injury, various extrahepatic metabolic disorders impact the natural history of the disease, clinical outcomes, and the efficacy of antiviral therapy. The presence of steatosis, recently redefined as metabolic-associated fatty liver disease (MAFLD), is a common feature in HCV-infected patients, induced by host and/or viral factors. Most chronic HCV-infected (CHC) patients have mild steatosis within the periportal region of the liver with an estimated prevalence of 40% to 86%. Indeed, this is higher than the 19% to 50% prevalence observed in patients with other chronic liver diseases such as chronic hepatitis B (CHB). The histological manifestations of HCV infection are frequently observed in genotype 3 (G-3), where relative to other genotypes, the prevalence and severity of steatosis is also increased. Steatosis may independently influence the treatment efficacy of either interferon-based or interferon-free antiviral regimens. This review aimed to provide updated evidence of the prevalence and risk factors behind HCV-associated steatosis, as well as explore the impact of steatosis on HCV-related outcomes.
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Affiliation(s)
- Phumelele Yvonne Siphepho
- Program in Tropical Medicine, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (P.Y.S.); (M.-L.Y.)
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
| | - Yi-Ting Liu
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
| | - Ciniso Sylvester Shabangu
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Jee-Fu Huang
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Ming-Lung Yu
- Program in Tropical Medicine, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (P.Y.S.); (M.-L.Y.)
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Shu-Chi Wang
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
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