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Giannini EG, Mangia A, Morisco F, Toniutto P, Avogaro A, Fagiuoli S, Borghi C, Frigerio F, Nugnes M, Veronesi C, Cappuccilli M, Andretta M, Bacca M, Barbieri A, Bartolini F, Chinellato G, Ciaccia A, Lombardi R, Mancini D, Pagliaro R, Ubertazzo L, Degli Esposti L, Ponziani FR. A Real-World Analysis of the Population with Hepatitis C Virus Infection Affected by Type 2 Diabetes in Italy: Patients' Characteristics, Comorbidity Profiles and Treatment Patterns. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:614. [PMID: 40282905 PMCID: PMC12028345 DOI: 10.3390/medicina61040614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 03/23/2025] [Accepted: 03/24/2025] [Indexed: 04/29/2025]
Abstract
Background and Objectives: HCV infection represents a main risk factor for type 2 diabetes (T2D). This real-world analysis investigated the HCV-positive (HCV+) population with a T2D co-diagnosis in Italy. Methods: From 2017 to 2021, HCV+ patients were identified from administrative databases and stratified into T2D-HCV+ and HCV+-only cohorts in the presence/absence of a T2D diagnosis. Both cohorts were further divided by treatment with direct-acting antivirals (DAAs). The subgroups were compared for demographic variables, comorbidity profiles, most frequent hospitalizations, and drug prescriptions before inclusion. A sensitivity analysis was performed on patients included after 2019, the year of widespread use of pangenotypic DAAs. Results: Considering HCV+ patients aged ≥55 years, T2D-HCV+ patients (N = 1277) were significantly (p < 0.001) older than HCV+-only (N = 6576) ones and burdened by a worse comorbidity profile (average Charlson index: 1.4 vs. 0.3, p < 0.05). Moreover, regardless of T2D presence, DAA-treated patients were older (p < 0.001) and had a worse Charlson index than the untreated ones. T2D-HCV+ patients showed tendentially higher hospitalization rates and co-medication prescriptions compared to the HCV+-only patients. After 2019, a trend towards reduced co-medication use in DAA-treated patients was noticed, especially antibiotics and cardiovascular drugs. Conclusions: The co-presence of T2D in HCV+ patients resulted in a worse clinical status, as confirmed by the more frequent requirement of hospitalizations and complex polypharmacy regimens.
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Affiliation(s)
| | - Alessandra Mangia
- Liver Unit, Department of Medical Sciences, Fondazione “Casa Sollievo della Sofferenza” IRCCS, 71013 San Giovanni Rotondo, Italy;
| | - Filomena Morisco
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80138 Naples, Italy;
| | - Pierluigi Toniutto
- Hepatology and Liver Transplantation Unit, University of Udine, 33100 Udine, Italy;
| | - Angelo Avogaro
- Department of Medicine, Section of Diabetes and Metabolic Diseases, University of Padova, 35128 Padua, Italy;
| | - Stefano Fagiuoli
- Gastroenterology Hepatology and Transplantation Unit, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy;
- Gastroenterology, Department of Medicine, University of Milan Bicocca, 20126 Milan, Italy
| | - Claudio Borghi
- Department of Medical and Surgical Sciences, IRCCS AOU S. Orsola di Bologna, 40138 Bologna, Italy;
| | | | - Marta Nugnes
- CliCon S.r.l. Società Benefit, Health, Economics & Outcomes Research, 40137 Bologna, Italy; (M.N.); (C.V.); (M.C.); (L.D.E.)
| | - Chiara Veronesi
- CliCon S.r.l. Società Benefit, Health, Economics & Outcomes Research, 40137 Bologna, Italy; (M.N.); (C.V.); (M.C.); (L.D.E.)
| | - Maria Cappuccilli
- CliCon S.r.l. Società Benefit, Health, Economics & Outcomes Research, 40137 Bologna, Italy; (M.N.); (C.V.); (M.C.); (L.D.E.)
| | - Margherita Andretta
- UOC Assistenza Farmaceutica Territoriale, Azienda ULSS 8 Berica, 36100 Vicenza, Italy; (M.A.); (G.C.)
| | - Marcello Bacca
- Programmazione e Controllo di Gestione, ASL Brindisi, 72100 Brindisi, Italy;
| | - Antonella Barbieri
- SC Farmaceutica Territoriale, Azienda Sanitaria Locale di Vercelli (ASL VC), 13100 Vercelli, Italy;
| | - Fausto Bartolini
- Dipartimento Farmaceutico USL Umbria 2, Coordinatore della Cabina di Regia Regione Umbria Sulla Governance Farmaceutica, 05100 Terni, Italy;
| | - Gianmarco Chinellato
- UOC Assistenza Farmaceutica Territoriale, Azienda ULSS 8 Berica, 36100 Vicenza, Italy; (M.A.); (G.C.)
| | - Andrea Ciaccia
- Servizio Farmaceutico Territoriale, ASL Foggia, 71100 Foggia, Italy; (A.C.); (R.L.)
| | - Renato Lombardi
- Servizio Farmaceutico Territoriale, ASL Foggia, 71100 Foggia, Italy; (A.C.); (R.L.)
| | - Daniela Mancini
- UOSD Pianificazione Acquisti Farmaci e Beni Sanitari, ASL Brindisi, 72100 Brindisi, Italy;
| | - Romina Pagliaro
- UOC Farmaceutica Territoriale, Azienda Sanitaria Locale Roma 5, 00019 Tivoli, Italy;
| | | | - Luca Degli Esposti
- CliCon S.r.l. Società Benefit, Health, Economics & Outcomes Research, 40137 Bologna, Italy; (M.N.); (C.V.); (M.C.); (L.D.E.)
| | - Francesca Romana Ponziani
- Liver Unit, CEMAD-Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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Sallam M, Khalil R. Contemporary Insights into Hepatitis C Virus: A Comprehensive Review. Microorganisms 2024; 12:1035. [PMID: 38930417 PMCID: PMC11205832 DOI: 10.3390/microorganisms12061035] [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: 04/30/2024] [Revised: 05/15/2024] [Accepted: 05/20/2024] [Indexed: 06/28/2024] Open
Abstract
Hepatitis C virus (HCV) remains a significant global health challenge. Approximately 50 million people were living with chronic hepatitis C based on the World Health Organization as of 2024, contributing extensively to global morbidity and mortality. The advent and approval of several direct-acting antiviral (DAA) regimens significantly improved HCV treatment, offering potentially high rates of cure for chronic hepatitis C. However, the promising aim of eventual HCV eradication remains challenging. Key challenges include the variability in DAA access across different regions, slightly variable response rates to DAAs across diverse patient populations and HCV genotypes/subtypes, and the emergence of resistance-associated substitutions (RASs), potentially conferring resistance to DAAs. Therefore, periodic reassessment of current HCV knowledge is needed. An up-to-date review on HCV is also necessitated based on the observed shifts in HCV epidemiological trends, continuous development and approval of therapeutic strategies, and changes in public health policies. Thus, the current comprehensive review aimed to integrate the latest knowledge on the epidemiology, pathophysiology, diagnostic approaches, treatment options and preventive strategies for HCV, with a particular focus on the current challenges associated with RASs and ongoing efforts in vaccine development. This review sought to provide healthcare professionals, researchers, and policymakers with the necessary insights to address the HCV burden more effectively. We aimed to highlight the progress made in managing and preventing HCV infection and to highlight the persistent barriers challenging the prevention of HCV infection. The overarching goal was to align with global health objectives towards reducing the burden of chronic hepatitis, aiming for its eventual elimination as a public health threat by 2030.
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Affiliation(s)
- Malik Sallam
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan
- Department of Clinical Laboratories and Forensic Medicine, Jordan University Hospital, Amman 11942, Jordan
| | - Roaa Khalil
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan
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Haghtalab A, Hejazi M, Goharnia N, Yekanlou A, Hazhir K, Barghi A, Bazzaz Z, Allahverdizadeh I, GhalibafSabbaghi A. Investigating the correlation between prominent viruses and hematological malignancies: a literature review. Med Oncol 2024; 41:102. [PMID: 38546893 DOI: 10.1007/s12032-024-02345-1] [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: 01/11/2024] [Accepted: 02/23/2024] [Indexed: 04/02/2024]
Abstract
Extensive research has been conducted on the correlation between viral infections and hematological cancers ever since the identification of the Rous Sarcoma Virus as a cancer-causing agent. Numerous viruses, such as the Epstein-Barr virus, hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human T-lymphotropic virus 1, and severe acute respiratory syndrome-related coronavirus 2, have been identified as potential contributors to the development and progression of cancer by disrupting normal cellular processes. Different viruses are associated with distinct forms of blood cancers, each exhibiting unique infection mechanisms, pathogenesis, and clinical symptoms. Understanding these connections is crucial for the development of effective prevention and treatment strategies. Healthcare professionals who possess a solid understanding of these associations can offer precise treatments and closely monitor potential complications in individuals with blood cancers and viral infections. By leveraging this information, healthcare providers can optimize patient care and improve outcomes for those affected by both viral infections and hematological cancers.
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Affiliation(s)
- Arian Haghtalab
- Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
| | - Milad Hejazi
- Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Naeem Goharnia
- Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Ali Yekanlou
- Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Kousha Hazhir
- Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Asma Barghi
- Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Zahra Bazzaz
- Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
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Abdel-Samiee M, Youssef MI, Elghamry F, Bazeed M, Al-Shorbagy M, Shalaby H, Shabana H, Abdelsameea E, Lashin HES, El Zamek HMF, Esam T, Alwaseef MAA, Helmy HA, Almarshad F, Khalaf FA, Yossef BWA, Kassem A, Gabr BM, Abdelfattah A, S AboShabaan H, Aboufarrag GA, Omar MM, Bakeer MS, Imam MS, Ibrahim ES, Kamel SY, Allisy T, Mohammed OS, Farahat A, El-Khayat MM, Sekeen MAH, Zaher EM, Said A, Abuamer A, Elmahdi E. A multicentric and nationwide predictive study role of T cell sub-population in the prevalence and prognosis of cryoglobulinemia among genotype 4 chronic hepatitis C patients. J Med Virol 2023; 95:e29248. [PMID: 38108641 DOI: 10.1002/jmv.29248] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 11/01/2023] [Accepted: 11/11/2023] [Indexed: 12/19/2023]
Abstract
The infection caused by the hepatitis C virus (HCV) is a significant global health concern. The prevailing genotype of HCV in Egypt is 4a, commonly referred to as GT-4a. A significant proportion exceeding 50% of patients infected with HCV experience extrahepatic manifestations (EHMs), encompassing a diverse range of clinical presentations. These manifestations, including essential mixed cryoglobulinemia (MC), can serve as initial and solitary indicators of the disease. The complete understanding of the pathogenesis of EHM remains unclear, with autoimmune phenomena being recognized as the primary causative factor. In this study, we examined the predictive significance of T-cell subpopulations in relation to the occurrence and prognosis of cryoglobulinemia in HCV patients. A total of 450 CHC genotype four treatment naïve patients were enrolled in this analytic cross-sectional study after thorough clinical, laboratory, and radiological examinations. All patients underwent laboratory investigations, including testing for cryoglobulin antibodies and measurements of CD4 and CD8 levels; two groups were described according to their test results: Group 1 consists of patients who have tested positive for cryoglobulin antibodies and Group 2 consists of patients who have tested negative for cryoglobulin antibodies. The exclusion criteria encompassed individuals with HIV infection or chronic HBV infection. Additionally, pelvi-abdominal ultrasonography was performed. Our study included 450 treatment naïve CHC patients (59% male, mean age 50.8 years). The patients were categorized according to their cryoglobulin antibodys test results into two groups: group A, CHC patients with cryoglobulin antibodies (Abs) negative (364 patients), and group B, CHC patients with cryoglobulin Ab positive (86 patients). Group B demonstrated a higher average age, elevated international normalized ratio, more prolonged duration of HCV infection, lower albumin, higher alanine aminotransferase, higher aspartate aminotransferase, higher bilirubin, lower CD8, lower CD4, and lower CD4:CD8 ratio. In contrast, 27 out of 86 (31.40%) patients in group B had symptoms; 85.8% had purpura and arthralgia, 74.3% had paresthesias, 86.7% had weakness, and 12.2% had non-Hodgkin's lymphoma. The levels of CD4 and CD8 were found to be decreased in chronic HCV patients with MC. T-cell subpopulation serves as a reliable indicator for assessing the prevalence and prognosis of MC in individuals with genotype 4 chronic hepatitis C. However, additional research is needed to further understand the development and spread of various emerging infectious diseases. Nevertheless, it is noteworthy that a critical threshold may exist beyond which EHM reaches a point of no return.
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Affiliation(s)
- Mohamed Abdel-Samiee
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, Egypt
| | - Mohamed I Youssef
- Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Fathy Elghamry
- Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Mahmoud Bazeed
- Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Mohamed Al-Shorbagy
- Department of Clinical Pathology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Helmy Shalaby
- Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Hossam Shabana
- Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
- Department of Internal Medicine, College of Medicine, Shaqra University, Dawadmi, Saudi Arabia
| | - Eman Abdelsameea
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, Egypt
| | | | | | - Tarek Esam
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, Egypt
| | | | - Housam Ahmed Helmy
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, Egypt
| | - Feras Almarshad
- Department of Internal Medicine, College of Medicine, Shaqra University, Dawadmi, Saudi Arabia
| | - Fatma A Khalaf
- Department of Clinical Biochemistry, National Liver Institute, Menoufia University, Shebin El-Kom, Egypt
| | | | - Arafat Kassem
- Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Basant Mostafa Gabr
- Department of Microbiology and Immunology, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Ahmed Abdelfattah
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, Egypt
| | - Hind S AboShabaan
- Department of Clinical Pathology, National Liver Institute, Menoufia University, Menoufia, Egypt
| | | | - Marwa M Omar
- Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Shebin El-Kom, Egypt
| | - Mohammed Saied Bakeer
- Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Mohammed S Imam
- Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | | | - Shimaa Y Kamel
- Department of Tropical Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Talaat Allisy
- Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Omima Sayed Mohammed
- Department of Microbiology, College of Medicine, Najran University, Najran, Saudi Arabia
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Ali Farahat
- Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Mohsen M El-Khayat
- Department of Tropical Medicine, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt
| | | | - Eman Mohammed Zaher
- Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Shebin El-Kom, Egypt
| | - Ashraf Said
- Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Ahmed Abuamer
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, Egypt
| | - Essam Elmahdi
- Department of Internal Medicine, College of Medicine, Shaqra University, Dawadmi, Saudi Arabia
- Department of Internal medicine, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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Chen H, Du P, Yang T, Xu X, Cui T, Dai Y. Hepatitis C virus infection is associated with high risk of breast cancer: a pooled analysis of 68,014 participants. Front Oncol 2023; 13:1274340. [PMID: 37901319 PMCID: PMC10613072 DOI: 10.3389/fonc.2023.1274340] [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: 08/08/2023] [Accepted: 09/28/2023] [Indexed: 10/31/2023] Open
Abstract
Introduction Breast cancer is the most common malignancy among women. Previous studies had shown that hepatitis C virus (HCV) infection might serve as a risk factor for breast cancer, while some studies failed to find such an association. Methods In this study, we presented a first attempt to capture and clarify this clinical debate via a cumulative analysis (registration ID: CRD42023445888). Results After systematically searching and excluding the irrelevant publications, five case-control or cohort studies were finally included. The synthetic effect from the eligible studies showed that patients with HCV infection had a significantly higher prevalence of breast cancer than non-HCV infected general population (combined HR= 1.382, 95%CI: 1.129 to 1.692, P=0.002). There was no evidence of statistical heterogeneity during this pooled analysis (I2 = 13.2%, P=0.33). The sensitivity analyses confirmed the above findings. No significant publication bias was observed among the included studies. The underlying pathophysiological mechanisms for this relationship might be associated with persistent infection/inflammation, host immune response, and the modulation of HCV-associated gene expression. Discussion Though the causal association between HCV infection and breast cancer did not seem quite as strong, screening for HCV might enable the early detection of breast cancer and help to prevent the progression of the disease. Since the topic of this study remains a matter of clinical debate, further studies are still warranted to validate this potential association. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023445888.
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Affiliation(s)
- Haiping Chen
- Department of Infectious Diseases, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, China
| | - Pei Du
- Department of Gynecology and Obstetrics, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, China
| | - Tianyao Yang
- Department of Thyroid and Breast Surgery, Tiantai People's Hospital, Taizhou, Zhejiang, China
| | - Xueyuan Xu
- Department of Gynecology and Obstetrics, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, China
| | - Tianyang Cui
- Department of Clinical Medical School, Taizhou University, Taizhou, Zhejiang, China
| | - Yuhang Dai
- Department of Gastroenterology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
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Fayed HL, Shahin AA, El-Bohy AEMM, Younis SS. Comparative assessment of hepatitis C virus-related arthritis and rheumatoid arthritis: Relation to clinical, serologic and ultrasonographic characteristics. THE EGYPTIAN RHEUMATOLOGIST 2023. [DOI: 10.1016/j.ejr.2023.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
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Strebe J, Rich NE, Wang L, Singal AG, McBryde J, Silva M, Jackson V, Fullington H, Villarreal DL, Reyes S, Flores B, Jain MK. Patient Navigation Increases Linkage to Care and Receipt of Direct-acting Antiviral Therapy in Patients with Hepatitis C. Clin Gastroenterol Hepatol 2023; 21:988-994.e2. [PMID: 35577048 DOI: 10.1016/j.cgh.2022.04.031] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 04/09/2022] [Accepted: 04/21/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Patient navigation interventions can improve health outcomes in underserved, low-income, and racial and ethnic minority groups, who often experience health disparities. We examined the effectiveness of patient navigation to improve linkage to hepatitis C virus (HCV) treatment receipt in a socioeconomically disadvantaged, racially diverse patient population. METHODS We performed a pre-post analysis evaluating the effectiveness of a patient navigation program among baby boomers who tested positive for HCV in a safety-net health system. The usual care group (June 2013 to May 2015) and patient navigation group (January 2016 to December 2017) were balanced using a stabilized inverse probability of treatment weighting approach. We used logistic regression analyses to evaluate associations between patient navigation and linkage to care for HCV treatment evaluation, treatment initiation, and sustained virologic response. RESULTS Among 1353 patients (62% black, 61% uninsured, 16% homeless), 769 were in the usual care group, and 584 were in the patient navigation group. The patient navigation group had significantly higher odds of linkage to care (odds ratio [OR], 3.7; 95% confidence interval [CI], 2.9-4.8) and treatment initiation (OR, 3.2; 95% CI, 2.3-4.2) within 6 months. The patient navigation group continued to have increased linkage to care (OR, 3.4; 95% CI, 2.7-4.3) and treatment initiation (OR 2.3; 95% CI, 1.7-3.0) at 12 months. However, there was no significant difference in sustained virologic response between the groups (86.9% vs 86.1%; P = .78). CONCLUSIONS Patient navigation was associated with significantly increased linkage to care and treatment initiation among patients with HCV infection. Patient navigation programs can be used to promote HCV elimination among traditionally difficult-to-reach patient populations.
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Affiliation(s)
| | - Nicole E Rich
- Parkland Health and Hospital System, Dallas, Texas; Department of Internal Medicine, Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas
| | - Li Wang
- Department of Internal Medicine, Population and Data Sciences, UT Southwestern Medical Center, Dallas, Texas
| | - Amit G Singal
- Parkland Health and Hospital System, Dallas, Texas; Department of Internal Medicine, Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas; Department of Internal Medicine, Population and Data Sciences, UT Southwestern Medical Center, Dallas, Texas
| | - Jennifer McBryde
- Parkland Health and Hospital System, Dallas, Texas; Department of Internal Medicine, Population and Data Sciences, UT Southwestern Medical Center, Dallas, Texas
| | - Mauro Silva
- Parkland Health and Hospital System, Dallas, Texas
| | | | - Hannah Fullington
- Department of Internal Medicine, Population and Data Sciences, UT Southwestern Medical Center, Dallas, Texas
| | - Deyaun L Villarreal
- Department of Internal Medicine, Population and Data Sciences, UT Southwestern Medical Center, Dallas, Texas
| | - Stephanie Reyes
- Department of Internal Medicine, Population and Data Sciences, UT Southwestern Medical Center, Dallas, Texas
| | - Bertha Flores
- School of Nursing, UT Health San Antonio, San Antonio, Texas
| | - Mamta K Jain
- Parkland Health and Hospital System, Dallas, Texas; Department of Internal Medicine, Division of Infectious Disease and Geographic Medicine, UT Southwestern Medical Center, Dallas, Texas.
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Fagiuoli S, Toniutto P, Coppola N, Ancona DD, Andretta M, Bartolini F, Ferrante F, Lupi A, Palcic S, Rizzi FV, Re D, Alvarez Nieto G, Hernandez C, Frigerio F, Perrone V, Degli Esposti L, Mangia A. Italian Real-World Analysis of the Impact of Polypharmacy and Aging on the Risk of Multiple Drug-Drug Interactions (DDIs) in HCV Patients Treated with Pangenotypic Direct-Acting Antivirals (pDAA). Ther Clin Risk Manag 2023; 19:57-65. [PMID: 36699017 PMCID: PMC9868280 DOI: 10.2147/tcrm.s394467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 12/29/2022] [Indexed: 01/19/2023] Open
Abstract
Purpose The study aims at investigating the impact of polymedication and aging in the prevalence of multiple drug-drug interactions (DDIs) on HCV patients treated with sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB). Patients and Methods This is a retrospective analysis based on administrative data covering around 6.9 million individuals. Patients treated with SOF/VEL or GLE/PIB over November 2017-March 2020 were included. Index date corresponded to SOF/VEL or GLE/PIB first prescription during such period; patients were followed up for treatment duration. Analyses were then focused on patients with ≥2 comedications at risk of multiple DDIs. The severity and the effect of multiple DDI were identified using the Liverpool University tool. Results A total of 2057 patients with SOF/VEL and 2128 with GLE/PIB were selected. Mean age of SOF/VEL patients was 58.5 years, higher than GLE/PIB ones (52.5 years) (p < 0.001), and patients >50 years were more present in SOF/VEL vs GLE/PIB cohorts: 72% vs 58%, (p < 0.001). Most prescribed co-medications were cardiovascular, alimentary and nervous system drugs. Proportion of patients with ≥2 comedications was higher in SOF/VEL compared to GLE/PIB cohort (56.5% vs 32.3%, p < 0.001). Those at high-risk of multiple DDIs accounted for 11.6% (N = 135) of SOF/VEL and 19.6% (N = 135) of GLE/PIB (p < 0.001) patients with ≥2 comedications. Among them, the potential effect of DDI was a decrease of DAA serum levels (11% of SOF/VEL and GLE/PIB patients) and an increased concentration of comedication serum levels (14% of SOF/VEL and 42% of GLE/PIB patients). Conclusion This real-world analysis provided a thorough characterization on the burden of polymedication regimens in HCV patients treated with SOF/VEL or GLE/PIB that expose such patients to an increased risk of DDIs. In our sample population, SOF/VEL regimen was more frequently detected on elderly patients and on those with ≥2 comedications at risk of multi-DDI, ie, among patients characterized by higher rates of comorbidities and polypharmacy.
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Affiliation(s)
- Stefano Fagiuoli
- Department of Medicine and Surgery, University of Milan Bicocca & Gastroenterology Hepatology and Transplantation Unit, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Pierluigi Toniutto
- Hepatology and Liver Transplantation Unit, Azienda Ospedaliero Universitaria, Udine, Italy
| | - Nicola Coppola
- Infectious Diseases Unit, University of Campania L. Vanvitelli, Naples, Italy
| | | | - Margherita Andretta
- UOC Assistenza Farmaceutica Territoriale, Azienda Ulss 8 Berica, Vicenza, Italy
| | | | - Fulvio Ferrante
- Dipartimento Diagnostica Ed Assistenza Farmaceutica – ASL Frosinone, Frosinone, Italy
| | | | - Stefano Palcic
- Farmaceutica Territoriale- Azienda Sanitaria Universitaria Integrata Giuliano-Isontina (ASUGI), Trieste, Italy
| | | | - Davide Re
- Servizio Farmaceutico Territoriale ASL Teramo, Teramo, Italy
| | | | | | | | - Valentina Perrone
- Clicon S.r.l., Health Economics and Outcomes Research, Bologna, Italy
| | - Luca Degli Esposti
- Clicon S.r.l., Health Economics and Outcomes Research, Bologna, Italy,Correspondence: Luca Degli Esposti, CliCon S.r.l. Società Benefit, Health, Economics & Outcomes Research, Via Murri, 9, Bologna, 40137, Italy, Tel +390544 38393, Email
| | - Alessandra Mangia
- Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Bergamo, 24127, Italy
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Marascio N, De Caro C, Quirino A, Mazzitelli M, Russo E, Torti C, Matera G. The Role of the Microbiota Gut-Liver Axis during HCV Chronic Infection: A Schematic Overview. J Clin Med 2022; 11:5936. [PMID: 36233804 PMCID: PMC9572099 DOI: 10.3390/jcm11195936] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 10/03/2022] [Accepted: 10/04/2022] [Indexed: 11/30/2022] Open
Abstract
Hepatitis C virus (HCV) still represents one of the most important worldwide health care problems. Since 2011, direct-acting antiviral (DAA) drugs have increased the number of people who have achieved a sustained virological response (SVR). Even if the program to eradicate HCV by 2030 is still ongoing, the SARS-CoV-2 pandemic has created a delay due to the reallocation of public health resources. HCV is characterized by high genetic variability and is responsible for hepatic and extra-hepatic diseases. Depending on the HCV genotype/subtype and comorbidities of patients, tailored treatment is necessary. Recently, it has been shown that liver damage impacts gut microbiota, altering the microbial community (dysbiosis) during persistent viral replication. An increasing number of studies are trying to clarify the role of the gut-liver axis during HCV chronic infection. DAA therapy, by restoring the gut microbiota equilibrium, seems to improve liver disease progression in both naïve and treated HCV-positive patients. In this review, we aim to discuss a snapshot of selected peer-reviewed papers concerning the interplay between HCV and the gut-liver axis.
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Affiliation(s)
- Nadia Marascio
- Clinical Microbiology Unit, Department of Health Science, “Magna Graecia” University, 88100 Catanzaro, Italy
| | - Carmen De Caro
- System and Applied Pharmacology, Department of Health Science, “Magna Graecia” University, 88100 Catanzaro, Italy
| | - Angela Quirino
- Clinical Microbiology Unit, Department of Health Science, “Magna Graecia” University, 88100 Catanzaro, Italy
| | - Maria Mazzitelli
- Infectious and Tropical Diseases Unit, University Hospital of Padua, 35128 Padua, Italy
| | - Emilio Russo
- System and Applied Pharmacology, Department of Health Science, “Magna Graecia” University, 88100 Catanzaro, Italy
| | - Carlo Torti
- Infectious and Tropical Diseases Unit, Department of Medical and Surgical Sciences, “Magna Graecia” University, 88100 Catanzaro, Italy
| | - Giovanni Matera
- Clinical Microbiology Unit, Department of Health Science, “Magna Graecia” University, 88100 Catanzaro, Italy
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10
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Azatyan V, Yessayan L, Sargsyan A, Khachatryan A, Ghevondyan T, Shmavonyan M, Melik-Andreasyan G, Porksheyan K, Manrikyan M. Morphological Changes in the Oral Mucous Membrane in Viral Hepatitis C Patients: A Cross-Sectional Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19159003. [PMID: 35897373 PMCID: PMC9330065 DOI: 10.3390/ijerph19159003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 07/19/2022] [Accepted: 07/21/2022] [Indexed: 02/01/2023]
Abstract
Background: The objective was to reveal the most typical changes in oral mucosa in HCV patients and compare them with those in HCV negative patients. Methods: The study involved 96 HCV patients and 100 patients without HCV who applied to a dental clinic. The content of cytokines IL-2, IL-4, IL-10 and ɤ-INF in the oral fluid was determined by ELISA. Buccal mucosa and gums biopsies passed histological examination. An immunohistochemical study of mucous membrane biopsies was performed using monoclonal mouse antibodies to CD3+ and CD20+. Results: The HCV patients group included 96 (63.5% males), and the non-HCV group included 100 subjects (62.0% males) with lesions of the oral mucous membrane. The lesions of lips and oral mucosa were more frequent in HCV than in the non-HCV group—e.g., erosion (13.5% vs. 1%), cracks in the mouth corners (42.7% vs. 0%), changes in the oral mucosa surface (89.6% vs. 3.0%), hemorrhages (78.1% vs. 0%), etc. The pro-inflammatory IL-2 level was higher and anti-inflammatory IL-4 level was lower in HCV patients compared with those in the non-HCV group. Conclusions: Morphological changes developed in the microvasculature both worsen the tissue trophism and accelerate the healing with differentiation into coarse-fibrous connective tissue. Immunohistochemical findings indicated a decrease in local humoral immune response.
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Affiliation(s)
- Vahe Azatyan
- Department of Therapeutic Stomatology, Yerevan State Medical University (YSMU), 2 Koryun Str., Yerevan 0025, Armenia;
- Correspondence: ; Tel.: +374-91-326773
| | - Lazar Yessayan
- Department of Therapeutic Stomatology, Yerevan State Medical University (YSMU), 2 Koryun Str., Yerevan 0025, Armenia;
| | - Aelita Sargsyan
- Tuberculosis Research and Prevention Center, 6/2 Adonts Str., 100 Apt., Yerevan 0014, Armenia;
| | - Anna Khachatryan
- Department of Pathological Anatomy, Yerevan State Medical University (YSMU), 2 Koryun Str., Yerevan 0025, Armenia;
| | - Tigran Ghevondyan
- Laboratory of Histochemistry and Electron Microscopy, After Orbeli Institute of Physiology of National Academy of Sciences of Republic Armenia (NAoS RA), 22 Brothers Orbeli Str., Yerevan 0028, Armenia;
| | - Melanya Shmavonyan
- Department of Infectious Diseases, Yerevan State Medical University (YSMU), 2 Koryun Str., Yerevan 0025, Armenia;
| | - Gayane Melik-Andreasyan
- National Center of Disease Control and Prevention, Ministry of Health (MoH), 12 Mkhitar Heratsi Str., Yerevan 0025, Armenia;
| | - Kristina Porksheyan
- Department of Diagnostic Radiology, Yerevan State Medical University (YSMU), 2 Koryun Str., Yerevan 0025, Armenia;
| | - Mikael Manrikyan
- Department of Pediatric Dentistry and Orthodontics, Yerevan State Medical University (YSMU), 2 Koryun Str., Yerevan 0025, Armenia;
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11
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Rios DA, Casciato PC, Caldirola MS, Gaillard MI, Giadans C, Ameigeiras B, De Matteo EN, Preciado MV, Valva P. Chronic Hepatitis C Pathogenesis: Immune Response in the Liver Microenvironment and Peripheral Compartment. Front Cell Infect Microbiol 2021; 11:712105. [PMID: 34414132 PMCID: PMC8369367 DOI: 10.3389/fcimb.2021.712105] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 07/07/2021] [Indexed: 12/14/2022] Open
Abstract
Chronic hepatitis C (CHC) pathogenic mechanisms as well as the participation of the immune response in the generation of liver damage are still a topic of interest. Here, we evaluated immune cell populations and cytokines in the liver and peripheral blood (PB) to elucidate their role in CHC pathogenesis. B, CTL, Th, Treg, Th1, Th17, and NK cell localization and frequency were evaluated on liver biopsies by immunohistochemistry, while frequency, differentiation, and functional status on PB were evaluated by flow cytometry. TNF-α, IL-23, IFN-γ, IL-1β, IL-6, IL-8, IL-17A, IL-21, IL-10, and TGF-β expression levels were quantified in fresh liver biopsy by RT-qPCR and in plasma by CBA/ELISA. Liver CTL and Th1 at the lobular area inversely correlated with viral load (r = −0.469, p =0.003 and r = −0.384, p = 0.040). Treg correlated with CTL and Th1 at the lobular area (r = 0.784, p < 0.0001; r = 0.436, p = 0.013). Th17 correlated with hepatic IL-8 (r = 0.52, p < 0.05), and both were higher in advanced fibrosis cases (Th17 p = 0.0312, IL-8 p = 0.009). Hepatic cytokines were higher in severe hepatitis cases (IL-1β p = 0.026, IL-23 p = 0.031, IL-8 p = 0.002, TGF-β, p= 0.037). Peripheral NK (p = 0.008) and NK dim (p = 0.018) were diminished, while NK bright (p = 0.025) was elevated in patients vs. donors. Naïve Th (p = 0.011) and CTL (p = 0.0007) were decreased, while activated Th (p = 0.0007) and CTL (p = 0.0003) were increased. IFN-γ production and degranulation activity in NK and CTL were normal. Peripheral cytokines showed an altered profile vs. donors, particularly elevated IL-6 (p = 0.008) and TGF-β (p = 0.041). Total hepatic CTLs favored damage. Treg could not prevent fibrogenesis triggered by Th17 and IL-8. Peripheral T-lymphocyte differentiation stage shift, elevated cytokine levels and NK-cell count decrease would contribute to global disease.
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Affiliation(s)
- Daniela Alejandra Rios
- Laboratory of Molecular Biology, Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP), CONICET-GCBA, Pathology Division, Ricardo Gutiérrez Children's Hospital, Buenos Aires, Argentina
| | | | - María Soledad Caldirola
- Immunology Unit, Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP), CONICET-GCBA, Ricardo Gutiérrez Children's Hospital, Buenos Aires, Argentina
| | - María Isabel Gaillard
- Immunology Unit, Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP), CONICET-GCBA, Ricardo Gutiérrez Children's Hospital, Buenos Aires, Argentina
| | - Cecilia Giadans
- Laboratory of Molecular Biology, Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP), CONICET-GCBA, Pathology Division, Ricardo Gutiérrez Children's Hospital, Buenos Aires, Argentina
| | | | - Elena Noemí De Matteo
- Laboratory of Molecular Biology, Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP), CONICET-GCBA, Pathology Division, Ricardo Gutiérrez Children's Hospital, Buenos Aires, Argentina
| | - María Victoria Preciado
- Laboratory of Molecular Biology, Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP), CONICET-GCBA, Pathology Division, Ricardo Gutiérrez Children's Hospital, Buenos Aires, Argentina
| | - Pamela Valva
- Laboratory of Molecular Biology, Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP), CONICET-GCBA, Pathology Division, Ricardo Gutiérrez Children's Hospital, Buenos Aires, Argentina
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12
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Ohlendorf V, Schäfer A, Christensen S, Heyne R, Naumann U, Link R, Herold C, Schiffelholz W, Günther R, Cornberg M, Serfert Y, Maasoumy B, Wedemeyer H, Kraus MR. Only partial improvement in health-related quality of life after treatment of chronic hepatitis C virus infection with direct acting antivirals in a real-world setting-results from the German Hepatitis C-Registry (DHC-R). J Viral Hepat 2021; 28:1206-1218. [PMID: 34003549 DOI: 10.1111/jvh.13546] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 03/10/2021] [Accepted: 04/17/2021] [Indexed: 12/12/2022]
Abstract
Improvement of health-related quality of life (HRQoL) is frequently reported as a benefit when treating hepatitis C virus infection (HCV) with direct acting antivirals (DAA). As most of the available data were obtained from clinical trials, limited generalizability to the real-world population might exist. This study aimed to investigate the impact of DAA therapy on changes in HRQoL in a real-world setting. HRQoL of 1180 participants of the German Hepatitis C-Registry was assessed by Short-Form 36 (SF-36) questionnaires. Scores at post-treatment weeks 12-24 (FU12/24) were compared to baseline (BL). Changes of ≥2.5 in mental and physical component summary scores (MCS and PCS) were defined as a minimal clinical important difference (MCID). Potential predictors of HRQoL changes were analysed. Overall, a statistically significant increase in HRQoL after DAA therapy was observed, that was robust among various subgroups. However, roughly half of all patients failed to achieve a clinically important improvement in MCS and PCS. Low MCS (p < .001, OR = 0.925) and PCS (p < .001, OR = 0.899) BL levels were identified as predictors for achieving a clinically important improvement. In contrast, presence of fatigue (p = .023, OR = 1.518), increased GPT levels (p = .005, OR = 0.626) and RBV containing therapy regimens (p = .001, OR = 1.692) were associated with a clinically important decline in HRQoL after DAA therapy. In conclusion, DAA treatment is associated with an overall increase of HRQoL in HCV-infected patients. Nevertheless, roughly half of the patients fail to achieve a clinically important improvement. Especially patients with a low HRQoL seem to benefit most from the modern therapeutic options.
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Affiliation(s)
| | - Arne Schäfer
- Diabetes-Klinik Bad Mergentheim, Bad Mergentheim, Germany
| | - Stefan Christensen
- CIM Münster, Münster, Germany.,Department of Gastroenterology and Hepatology, Münster University Hospital (UKM), Münster, Germany
| | | | | | - Ralph Link
- MVZ-Offenburg GmbH /St. Josefs-Klinik, Offenburg, Germany
| | | | | | - Rainer Günther
- Department of Internal Medicine I, Universitätsklinikum Schleswig-Holstein (UKSH, Kiel, Germany
| | | | | | | | - Heiner Wedemeyer
- Hannover Medical School, Hannover, Germany.,Department of Internal Medicine I, Universitätsklinikum Schleswig-Holstein (UKSH, Kiel, Germany
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13
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Pisano MB, Giadans CG, Flichman DM, Ré VE, Preciado MV, Valva P. Viral hepatitis update: Progress and perspectives. World J Gastroenterol 2021; 27:4018-4044. [PMID: 34326611 PMCID: PMC8311538 DOI: 10.3748/wjg.v27.i26.4018] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 04/11/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
Viral hepatitis, secondary to infection with hepatitis A, B, C, D, and E viruses, are a major public health problem and an important cause of morbidity and mortality. Despite the huge medical advances achieved in recent years, there are still points of conflict concerning the pathogenesis, immune response, development of new and more effective vaccines, therapies, and treatment. This review focuses on the most important research topics that deal with issues that are currently being solved, those that remain to be solved, and future research directions. For hepatitis A virus we will address epidemiology, molecular surveillance, new susceptible populations as well as environmental and food detections. In the case of hepatitis B virus, we will discuss host factors related to disease, diagnosis, therapy, and vaccine improvement. On hepatitis C virus, we will focus on pathogenesis, immune response, direct action antivirals treatment in the context of solid organ transplantation, issues related to hepatocellular carcinoma development, direct action antivirals resistance due to selection of resistance-associated variants, and vaccination. Regarding hepatitis D virus, we describe diagnostic methodology, pathogenesis, and therapy. Finally, for hepatitis E virus, we will address epidemiology (including new emerging species), diagnosis, clinical aspects, treatment, the development of a vaccine, and environmental surveillance.
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Affiliation(s)
- María B Pisano
- Virology Institute, CONICET, School of Medical Sciences, National University of Córdoba, Cordoba X5016, Argentina
| | - Cecilia G Giadans
- Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP) CONICET-GCBA, Laboratory of Molecular Biology, Pathology Division, Ricardo Gutiérrez Children’s Hospital, CABA C1425, Buenos Aires, Argentina
| | - Diego M Flichman
- Institute of Biomedical Investigations in Retrovirus and AIDS (INBIRS), School of Medicine, University of Buenos Aires, CONICET, CABA C1121ABG, Buenos Aires, Argentina
| | - Viviana E Ré
- Virology Institute, CONICET, School of Medical Sciences, National University of Córdoba, Cordoba X5016, Argentina
| | - María V Preciado
- Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP) CONICET-GCBA, Laboratory of Molecular Biology, Pathology Division, Ricardo Gutiérrez Children’s Hospital, CABA C1425, Buenos Aires, Argentina
| | - Pamela Valva
- Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP) CONICET-GCBA, Laboratory of Molecular Biology, Pathology Division, Ricardo Gutiérrez Children’s Hospital, CABA C1425, Buenos Aires, Argentina
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14
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Yang Y, Jiang Z, Wu W, Ruan L, Yu C, Xi Y, Wang L, Wang K, Mo J, Zhao S. Chronic Hepatitis Virus Infection Are Associated With High Risk of Gastric Cancer: A Systematic Review and Cumulative Analysis. Front Oncol 2021; 11:703558. [PMID: 34307172 PMCID: PMC8297975 DOI: 10.3389/fonc.2021.703558] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 06/21/2021] [Indexed: 12/26/2022] Open
Abstract
Mounting studies demonstrated both chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infection might be associated not only with an increased risk of hepatocellular carcinoma but also extrahepatic malignancies, i.e., gastric cancer (GC). However, a quantitative result addressing the association between HBV/HCV infection and GC development is scarce. A systematic search to identify the eligible studies was performed in four databases, including MEDLINE, EMBASE, Cochrane Library, and the PsychINFO. The relationship between HBV/HCV infection and the risk of GC was quantified by calculating the hazard ratio (HR) with a 95% confidence interval (CI). More methodologies of this study were available in the PROSPERO (ID: CRD42021243719). Thirteen included studies involving 7,027,546 individuals (mean age, 42.6-71.9 years) were enrolled in the pooled analyses. Two articles provided the clinical data of both HBV and HCV infections. The proportion of high methodological quality studies was 76.9% (10/13). Synthetic results from 10 eligible studies of HBV showed that HBV infection was associated with a significantly higher risk of GC when compared with the healthy controls without HBV infection (pooled HR, 1.26; 95% CI, 1.08–1.47; P = 0.003; heterogeneity, I2 = 89.3%; P< 0.001). In line with this finding, the combined effect derived from five included studies of HCV also supported a significant positive association between chronic HBV infection and GC development (pooled HR, 1.88; 95% CI, 1.28–2.76; P = 0.001; heterogeneity, I2 = 74.7%; P = 0.003). In conclusion, both chronic HBV and HCV infections were related to a high risk of GC. The plausible mechanisms underlying such association might be correlated to HBV/HCV infection-induced persistent inflammation, immune dysfunction, and cirrhosis.
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Affiliation(s)
- Yusha Yang
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Zufu Jiang
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Weizhou Wu
- Department of Urology, Maoming People's Hospital, Maoming, China
| | - Libin Ruan
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Chengyang Yu
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Yuning Xi
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Liling Wang
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Kunpeng Wang
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Jinggang Mo
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Shankun Zhao
- Department of Urology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
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15
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HCV Infection and Chronic Renal Disease. SERBIAN JOURNAL OF EXPERIMENTAL AND CLINICAL RESEARCH 2021. [DOI: 10.2478/sjecr-2021-0010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Abstract
Chronic Hepatitis C virus (HCV) infection is defined as persistence of HCV RNA in the blood for more than six months. HCV is a major cause of chronic liver disease and cirrhosis. It’s serious public health problem, affects about 71 million people worldwide. HCV doesn’t destroy hepatocytes directly. It activates the host's innate and acquired immune system and causes liver injury indirectly. Behind hepatic, HCV can cause extra-hepatic manifestations. One of them is renal disease which can lead to end-stage renal disease, ESRD. The prevalence of HCV infection in patients on hemodialysis is high, ranging from 5% to 60%. HCV infection is a significant cause of morbidity and mortality in patients with ESRD on hemodialysis. In this review, we discuss HCV infection and chronic renal disease as comorbidities, their severity and outcome.
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16
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Chung JW, Choi HY, Ki M, Jang ES, Jeong SH. Comorbidities and Prescribed Medications in Korean Patients with Chronic Hepatitis C: A Nationwide, Population-Based Study. Gut Liver 2021; 15:295-306. [PMID: 32616682 PMCID: PMC7960981 DOI: 10.5009/gnl19387] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 03/16/2020] [Accepted: 04/13/2020] [Indexed: 12/16/2022] Open
Abstract
Background/Aims Extrahepatic comorbidities and comedication are important to consider in the treatment of chronic hepatitis C (CHC) patients with direct-acting antivirals (DAAs) due to the risk of drug-drug interaction (DDI) and the effect of comorbidities on clinical outcomes. This study aimed to investigate the detailed profiles of comorbidities and comedication among Korean CHC patients. Methods All adult patients (≥18 years old) with a primary diagnostic code of CHC in 2013 were selected from the National Health Insurance claims database. For each patient, all ICD-10 codes listed as primary or secondary diagnoses and all prescribed medications were collected. Results Among 47,104 CHC patients (median age, 57 years; male, 49.3%), 84.8% had at least one comorbidity for a mean number of 2.4, which increased with age. The most prevalent comorbidities were hypertension, esophagitis, dyslipidemia, diabetes mellitus, and peptic ulcer. Overall, 96.8% of the patients took at least one prescribed medication, with a mean of 8.1 medications/ year, and the three most common drug types were analgesics, gastrointestinal agents, and antibacterials. Use of at least one drug with a DDI risk category of "contraindicated medication" or "required dose-reduction/additional monitoring" was observed in 97% of the overall patients. The proportion of prescribed medications that were contraindicated with DAAs varied from 2.0% to 38.9% depending on the hepatitis C virus regimen. Conclusions The majority of CHC patients had comorbidities; almost all patients took multiple prescribed medications, the number of which increased with age, and significant DDI risk was present in 97% of this Korean patient cohort. Comorbidities and comedication profiles should be considered during DAA therapy.
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Affiliation(s)
- Jung Wha Chung
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Hwa Young Choi
- National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Korea
| | - Moran Ki
- National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Korea
| | - Eun Sun Jang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Sook-Hyang Jeong
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
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Metabolic Impact of Diabetes Mellitus Type 2 in Hepatitis C Virus Infected Patients. CURRENT HEALTH SCIENCES JOURNAL 2021; 47:405-411. [PMID: 35003773 PMCID: PMC8679152 DOI: 10.12865/chsj.47.03.11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 09/10/2021] [Indexed: 11/24/2022]
Abstract
OBJECTIVE Patients with chronic hepatitis C are subjected to a greater risk of cardiovascular disease and difficult to control diabetes mellitus type 2 (T2DM) comparatively to people that have never contracted Hepatitis C Virus (HCV). We aimed to investigate the impact of T2DM on HCV patients with the help of Fibromax test results compared to nonT2DM patients, and the metabolic differences between the 2 study groups. Our long term goals are to observe the long term impact of achieving systemic virusologic response (SVR) by means of Direct-Acting antivirals (DAA) between the 2 cohorts. RESEARCH DESIGN AND METHODS We selected a lot of 200 patients with HCV that will undergo interferon-free DAA-based antiviral treatment for HCV and we used the results of the Fibromax Test to compare the biological parameters of T2DM and nonT2DM patients. RESULTS Among patients with T2DM compared to NonT2DM there is a significant correlation on Steatotest, NashTest, GGT, Glycemia, body weight, height and BMI. Test also showed that 15,5% of the test group had elevated glycemia, indicating the probability of developing diabetes in the future. CONCLUSIONS Our results suggest that HCV patients that also have T2DM are subjected to a combined higher risk of accelerated steatosis development, steatohepatitis, added difficulty in controlling glycemic levels. All these previous elements combined with a prevalence for patients to be overweight have a negative metabolic impact. Eradication of HCV with the help of DAA is important in order to help improving the metabolic impact of diabetes on steatosis, steatohepatitis. An added benefit is better management of glycemic control by decreasing insulin use and eliminating one risk factor of T2DM.
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18
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Biciuşcă V, Popescu M, Petrescu IO, Stan IS, Durand P, Petrescu M, Velea R, Traşcă DM, Popescu IAS, Udriştoiu I, Mărginean CM, Tudoraşcu DR, Petrescu F. Hepatic pathological features in naïve patients with chronic hepatitis C who have developed thyroid disorder. ROMANIAN JOURNAL OF MORPHOLOGY AND EMBRYOLOGY = REVUE ROUMAINE DE MORPHOLOGIE ET EMBRYOLOGIE 2020; 61:1085-1097. [PMID: 34171058 PMCID: PMC8343494 DOI: 10.47162/rjme.61.4.11] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 06/21/2021] [Indexed: 01/20/2023]
Abstract
Knowing the hepatic pathological features encountered in patients with chronic hepatitis C (CHC) and the fact that extrahepatic manifestations occur only in people with certain characteristics of the immune system, we tried to evaluate, qualitatively and semi-quantitatively, the liver pathological aspects encountered in 96 patients with CHC, previously untreated with Interferon (naïve), who showed or did not show signs of thyroid disorder (TD), hospitalized in the 2nd Medical Clinic of the Emergency County Hospital, Craiova, Romania, within a period of five years (2007-2012). Following hormonal, immunological, and thyroid ultrasound investigations, 14 (14.58%) of the 96 patients showed signs of TD. The main clinical forms of TD in the studied patients with CHC were autoimmune thyroiditis and subclinical hypothyroidism. In the patients with CHC with TD, we found mild chronic hepatitis in 14.28% of cases, the appearance of moderate chronic hepatitis was found in 71.42% patients, and the appearance of severe chronic hepatitis was found in 14.28% patients, while in the patients with CHC without TD we found chronic mild hepatitis in 62.19% of cases, the appearance of moderate chronic hepatitis was met in 32.92% patients, and the appearance of severe chronic hepatitis was found in 4.87% of patients. Mild and moderate fibrosis were found only in CHC patients without TD in a percentage of 25.6% and 65.85%, respectively, while severe fibrosis was found at 12.19% among CHC patients without TD and 92.85% among CHC patients with TD. The pathological aspect of liver cirrhosis was found only in those with TD (7.14%). In conclusion, the pathological features which define the liver necroinflammatory process, as encountered at the pathological examination in CHC patients with TD are the same as in any active chronic hepatitis, the differences being represented by the higher percentage of the periportal and the preseptal necrosis (piecemeal necrosis), as well as by the higher score of portal inflammation. In addition, the severe hepatic fibrosis and the histopathological appearance of the liver cirrhosis have only defined the cases of CHC with TD.
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Affiliation(s)
- Viorel Biciuşcă
- Department of Internal Medicine, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania
| | - Mihaela Popescu
- Department of Endocrinology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania
| | - Ileana Octavia Petrescu
- Department of Pediatrics, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania
| | - Ionelia Sorina Stan
- Resident Physician, Department of Internal Medicine, Emergency County Hospital, Craiova, Romania
| | - Patricia Durand
- Resident Physician, Department of Internal Medicine, Filantropia Clinical Hospital, Craiova, Romania
| | - Mihai Petrescu
- Resident Physician, Department of Psychiatry, Neuropsychiatric Clinical Hospital, Craiova, Romania
| | - Rodica Velea
- Department of Modern Languages, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania
| | - Diana Maria Traşcă
- Department of Internal Medicine, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania
| | - Iulian Alin Silviu Popescu
- Department of Internal Medicine, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania
| | - Ion Udriştoiu
- Department of Psychiatry, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania
| | - Cristina Maria Mărginean
- Department of Medical Semiology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania
| | - Diana Rodica Tudoraşcu
- Department of Medical Semiology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania
| | - Florin Petrescu
- Department of Medical Semiology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania
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Liraglutide Inhibits Hepatitis C Virus Replication Through an AMP Activated Protein Kinase Dependent Mechanism. Int J Mol Sci 2019; 20:ijms20184569. [PMID: 31540136 PMCID: PMC6769880 DOI: 10.3390/ijms20184569] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2019] [Revised: 08/29/2019] [Accepted: 09/09/2019] [Indexed: 12/13/2022] Open
Abstract
Insulin resistance and diabetes are both associated with chronic hepatitis C virus (HCV) infection, and the glucagon-like peptide-1(GLP-1) receptor agonist, liraglutide, is a common therapy for diabetes. Our aim was to investigate whether liraglutide treatment can inhibit HCV replication. A cell culture-produced HCV infectious system was generated by transfection of in vitro-transcribed genomic JFH-1 ribonucleic acid (RNA) into Huh-7.5 cells. Total RNA samples were extracted to determine the efficiency of HCV replication. The Ava5 cells were treated with liraglutide and cell viability was calculated. A Western blot analysis of the protein expression was performed. The immunoreactive blot signals were also detected. Liraglutide activated GLP-1 receptors in the HCV infectious system, and inhibited subgenomic HCV RNA replication in the HuH-7.5 cells. The Western blot analysis revealed both HCV protein and replicon RNA were reduced after treatment with liraglutide in a dose-dependent manner. Liraglutide decreased the cell viability of HCV RNA at an optimum concentration of 120 μg/mL, activated the 5′ adenosine monophosphate-activated protein kinase (AMPK) and the phosphorylated- transducer of regulated cyclic adenosine monophosphate (CAMP) response element-binding protein 2 (TORC2), thereby decreasing the cell viability of phosphoenolpyruvate carboxykinase (PEPCK) and G6pase RNA Therefore, we conclude that liraglutide can inhibit HCV replication via an AMPK/TORC2-dependent pathway.
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Pérez-Matute P, Íñiguez M, Villanueva-Millán MJ, Recio-Fernández E, Vázquez AM, Sánchez SC, Morano LE, Oteo JA. Short-term effects of direct-acting antiviral agents on inflammation and gut microbiota in hepatitis C-infected patients. Eur J Intern Med 2019; 67:47-58. [PMID: 31221551 DOI: 10.1016/j.ejim.2019.06.005] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 06/09/2019] [Accepted: 06/10/2019] [Indexed: 02/07/2023]
Abstract
Liver damage is associated with gut dysbiosis. New direct-acting antiviral agents (DAAs) are able to eradicate hepatitis C virus (HCV) from the body. However, the short and medium-term effects of DAAs at gut level before advanced liver damage occurs have not been evaluated yet. Thus, we investigated the impact of HCV and DAAs on gut microbiota composition (GM) and systemic inflammation. To achieve this objective, twenty-three non HCV-infected controls and 22 HCV-infected patients were recruited. Only non-cirrhotic patients (fibrosis stage 0-3) were included to avoid the direct impact of cirrhosis and portal hypertension on gut. The HCV-groups were evaluated before the treatment, after completing DAAs treatment and after 3 months. Fecal bacterial 16S rDNA was ultrasequenced and several biochemical/metabolic/inflammatory parameters were quantified. HCV infection was accompanied by a significant increase in TNFα plasma levels. DAAs were able to reduce this increase, especially in lower fibrosis grades. HCV infection was not accompanied by dramatic changes in α-diversity and was not recovered after HCV negativization, although a complete restoration was observed in lower fibrosis degrees. Six phyla, 15 genera and 9 bacterial species resulted differentially abundant among the groups. These differences were almost blunted with lower fibrosis. In summary, neither the usage of DAAs nor 3 months in sustained viral response were able to counteract the changes induced by HCV at gut level. The partial restoration observed in inflammation and α-diversity was only observed in low fibrosis degrees. Thus, it is urgent to begin treatment with DAAs as soon as possible.
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Affiliation(s)
- Patricia Pérez-Matute
- Infectious Diseases, Microbiota and Metabolism Unit, Infectious Diseases Department, Center for Biomedical Research of La Rioja (CIBIR), Logroño, (La Rioja), Spain.
| | - María Íñiguez
- Infectious Diseases, Microbiota and Metabolism Unit, Infectious Diseases Department, Center for Biomedical Research of La Rioja (CIBIR), Logroño, (La Rioja), Spain.
| | - María J Villanueva-Millán
- Infectious Diseases, Microbiota and Metabolism Unit, Infectious Diseases Department, Center for Biomedical Research of La Rioja (CIBIR), Logroño, (La Rioja), Spain.
| | - Emma Recio-Fernández
- Infectious Diseases, Microbiota and Metabolism Unit, Infectious Diseases Department, Center for Biomedical Research of La Rioja (CIBIR), Logroño, (La Rioja), Spain.
| | | | - Sheila Castro Sánchez
- Fundación Biomédica Galicia Sur, Instituto de Investigación Sanitaria Galicia Sur, Vigo, (Galicia), Spain.
| | - Luís E Morano
- Fundación Biomédica Galicia Sur, Instituto de Investigación Sanitaria Galicia Sur, Vigo, (Galicia), Spain; Infectious Diseases Department, Hospital Universitario Álvaro Cunqueiro, Vigo, (Galicia), Spain.
| | - José A Oteo
- Infectious Diseases, Microbiota and Metabolism Unit, Infectious Diseases Department, Center for Biomedical Research of La Rioja (CIBIR), Logroño, (La Rioja), Spain; Infectious Diseases Department, Hospital Universitario San Pedro, Logroño, (La Rioja), Spain.
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Wu ZY, Li H, Li JR, Lv XQ, Jiang JD, Peng ZG. Farnesoid X receptor agonist GW4064 indirectly inhibits HCV entry into cells via down-regulating scavenger receptor class B type I. Eur J Pharmacol 2019; 853:111-120. [PMID: 30902657 DOI: 10.1016/j.ejphar.2019.03.033] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2018] [Revised: 03/08/2019] [Accepted: 03/18/2019] [Indexed: 02/06/2023]
Abstract
Farnesoid X receptor (FXR) agonists play important regulatory roles in bile acid, lipid and glucose metabolism in vitro and in vivo. Thus, FXR agonists exhibit potential therapeutic effects on metabolism-related diseases that are associated with extrahepatic manifestations induced by hepatitis C virus (HCV) infection. This study investigated the effect and mechanism of FXR agonist GW4064 against HCV in vitro to explore the potential application of FXR agonists. Results showed that GW4064 and other FXR agonists have potent antiviral activity against HCV in Huh7.5 cells. GW4064 down-regulated the expression of scavenger receptor class B type I protein via FXR and thereby indirectly inhibited HCV entry into cells, leading to interruption of HCV life cycle. GW4064 also exhibited synergistic anti-HCV effect with known direct-acting antiviral agents (DAAs) used in the clinic and remained sensitive to DAA-resistant HCV mutations. Therefore, FXR agonists are also a kind of antiviral agent, and might be helpful in treatment of HCV-induced hepatic and extrahepatic manifestations.
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Affiliation(s)
- Zhou-Yi Wu
- Laboratory of Antiviral Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
| | - Hu Li
- Laboratory of Antiviral Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
| | - Jian-Rui Li
- Laboratory of Antiviral Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; Key Laboratory of Biotechnology of Antibiotics, The National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
| | - Xiao-Qin Lv
- Laboratory of Antiviral Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
| | - Jian-Dong Jiang
- Laboratory of Antiviral Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; Key Laboratory of Biotechnology of Antibiotics, The National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
| | - Zong-Gen Peng
- Laboratory of Antiviral Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; Key Laboratory of Biotechnology of Antibiotics, The National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
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Drazilova S, Janicko M, Skladany L, Kristian P, Oltman M, Szantova M, Krkoska D, Mazuchova E, Piesecka L, Vahalova V, Rac M, Schreter I, Virag L, Koller T, Liptakova A, Ondrasova M, Jarcuska P. Glucose Metabolism Changes in Patients with Chronic Hepatitis C Treated with Direct Acting Antivirals. Can J Gastroenterol Hepatol 2018; 2018:6095097. [PMID: 30402450 PMCID: PMC6192081 DOI: 10.1155/2018/6095097] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2018] [Revised: 08/19/2018] [Accepted: 09/18/2018] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND AND AIMS Chronic hepatitis C is a systemic disease and type 2 diabetes mellitus (T2DM) belongs to more common extrahepatic. The aim of this study was to (i) explore the prevalence of impaired fasting glucose (IFG) and T2DM in patients with chronic hepatitis C, (ii) explore the effect of direct acting antivirals (DAA) treatment on the glycemia, and (iii) explore the factors that modulate the effect of DAA treatment on glycemia in patients with chronic hepatitis C. METHODS We performed a longitudinal retrospective observational study focused on the patients undergoing DAA treatment of chronic hepatitis C. Data about glycemia, history of diabetes, hepatitis C virus, treatment, and liver status, including elastography, were obtained at baseline (before treatment start), at the end of treatment and 12 weeks after the end of treatment. Patients were treated with various regimens of direct acting antivirals. RESULTS We included 370 patients; 45.9% had F4 fibrosis. At baseline, the prevalence of T2DM increased with the degree of fibrosis (F0-F2 14.4%, F3 21.3%, and F4 31.8%, p=0.004). Fasting glycemia also increased with the degree of fibrosis (F0-F2 5.75±0.18 F3 5.84±0.17, and F4 6.69±0.2 mmol/L, p=0.001). We saw significant decrease of glycemia after treatment in all patients, but patients without T2DM or IFG from 6.21±0.12 to 6.08±0.15 mmol/L (p=0.002). The decrease was also visible in treatment experienced patients and patients with Child-Pugh A cirrhosis. CONCLUSION We confirmed that the prevalence of either T2DM or IFG increases in chronic hepatitis C patients with the degree of fibrosis. The predictive factors for T2DM were, besides F4, fibrosis also higher age and BMI. Significant decrease of fasting glycemia after the DAA treatment was observed in the whole cohort and in subgroups of patients with T2DM, IFG, cirrhotic, and treatment experienced patients.
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Affiliation(s)
- Sylvia Drazilova
- Department of Internal Medicine, Hospital Poprad, Banícka 803/28, Poprad, 05801, Slovakia
| | - Martin Janicko
- 1st Department of Internal Medicine, PJ Safarik University, Faculty of Medicine and L Pasteur University Hospital, Trieda SNP 1, Kosice, 04001, Slovakia
| | - Lubomir Skladany
- 2nd Department of Internal Medicine, FD Roosevelt University Hospital, Ludvíka Svobodu 1, Banska Bystrica, 97517, Slovakia
| | - Pavol Kristian
- Department of Infectious Diseases and Travel Medicine, PJ Safarik Unversity, Faculty of Medicine and L Pasteur University Hospital, Rastislavova 43, Kosice, 04001, Slovakia
| | - Marian Oltman
- Center for Gastroenterology and Hepatology Thalion, Tomášikova 50/C, Bratislava, 83104, Slovakia
| | - Maria Szantova
- 3rd Department of Internal Medicine, Commenius University, Faculty of Medicine and University Hospital, Limbová 5, Bratislava, 83305, Slovakia
| | - Dusan Krkoska
- Department of Infectious Diseases and Travel Medicine, Commenius University, Jesenius Faculty of Medicine and University Hospital, Štefanovičova 689/3, Martin, 03601, Slovakia
| | - Eva Mazuchova
- Department of Infectious Diseases and Travel Medicine, Commenius University, Jesenius Faculty of Medicine and University Hospital, Štefanovičova 689/3, Martin, 03601, Slovakia
| | - Lubica Piesecka
- Department of Infectious Diseases, Teaching Hospital Nitra, Špitálska 6, Nitra, 95001, Slovakia
| | - Veronika Vahalova
- Department of Infectious Diseases, Teaching Hospital Nitra, Špitálska 6, Nitra, 95001, Slovakia
| | - Marek Rac
- Department of Internal Medicine, Teaching Hospital Nitra, Špitálska 6, Nitra, 95001, Slovakia
| | - Ivan Schreter
- Department of Infectious Diseases and Travel Medicine, PJ Safarik Unversity, Faculty of Medicine and L Pasteur University Hospital, Rastislavova 43, Kosice, 04001, Slovakia
| | - Ladislav Virag
- Department of Infectious Diseases and Travel Medicine, PJ Safarik Unversity, Faculty of Medicine and L Pasteur University Hospital, Rastislavova 43, Kosice, 04001, Slovakia
| | - Tomas Koller
- 5th Department of Internal Medicine, Commenius University, Faculty of Medicine and University Hospital, Ružinovská 6, Bratislava, 82606, Slovakia
| | - Adriana Liptakova
- Department of Microbiology, Commenius University, Faculty of Medicine and University Hospital, Špitálska 13, Bratislava, 81372, Slovakia
| | - Miriam Ondrasova
- Saint Elisabeth University of Health and Social Sciences, Palackého 1, Bratislava, 81000, Slovakia
| | - Peter Jarcuska
- 1st Department of Internal Medicine, PJ Safarik University, Faculty of Medicine and L Pasteur University Hospital, Trieda SNP 1, Kosice, 04001, Slovakia
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Turnes J, Domínguez-Hernández R, Casado MÁ. Value and innovation of direct-acting antivirals: long-term health outcomes of the strategic plan for the management of hepatitis C in Spain. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2018; 109:809-817. [PMID: 29152988 DOI: 10.17235/reed.2017.5063/2017] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVE To assess the long-term healthcare costs and health outcomes in association with the access to new direct-acting antivirals (DAAs), during the first year of the National Strategic Plan for Chronic Hepatitis C (SPCHC) in patients with chronic hepatitis C (CHC) in Spain. METHODS A decision tree and a lifetime Markov model were developed to simulate the natural history, morbidity, and mortality of a cohort of 51,900 patients with CHC before (pre-DAA strategy) and after (post-DAA strategy) access to DAAs, following SPCHC approval. The percentage of patients treated, transition probabilities, disease management costs, health state utility values, sustained virologic response rates and treatment costs were obtained from the literature and published data from Spain. The results were expressed in terms of costs (€, 2016), quality-adjusted life years (QALYs) and prevention of clinical events, with an annual discount rate of 3%. RESULTS The post-DAA strategy would prevent 8,667 cases of decompensated cirrhosis, 5,471 cases of hepatocellular carcinoma, 1,137 liver transplants and 9,608 liver-related deaths. The cohort of 51,900 patients would require investments of 1,606 and 1,230 million euros with the post-DAA and pre-DAA strategies, respectively. This would produce 819,674 and 665,703 QALYs. CONCLUSIONS The use of new DAA-based treatments in CHC patients during the first year after the implementation of the SPCHC significantly reduced long-term morbidity and mortality and increased quality of life; demonstrating that this plan is an efficient use of public health resources.
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Affiliation(s)
- Juan Turnes
- Department of Gastroenterology and Hepatology, Complejo Hospitalario Universitario de Pontevedra
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Drazilova S, Gazda J, Janicko M, Jarcuska P. Chronic Hepatitis C Association with Diabetes Mellitus and Cardiovascular Risk in the Era of DAA Therapy. Can J Gastroenterol Hepatol 2018; 2018:6150861. [PMID: 30186821 PMCID: PMC6110000 DOI: 10.1155/2018/6150861] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2018] [Accepted: 07/31/2018] [Indexed: 12/15/2022] Open
Abstract
Patients with chronic hepatitis C have both higher prevalence of diabetes mellitus type 2 (T2DM) and increased cardiovascular risk compared to never infected people. Sustained viral response (SVR) achievement led to decreasing incidence and prevalence of T2DM during the interferon era of HCV treatment. Currently, direct-acting antiviral drugs (DAA) are the gold standard for treating HCV infection, while yielding SVR in nearly all patients. In chronic HCV patients with T2DM (prediabetes most likely too), DAA therapy is associated with both better fasting glucose and glycated hemoglobin (HbA1C) controls; thus reducing pharmacotherapy in a certain part of patients is possible. Papers mentioned in the review confirmed DAA role in both total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) increase. This alteration was accompanied by an increase in high-density lipoprotein cholesterol (HDL-C) and a decrease in triglycerides (TG) verified by most of the studies. However, the clinical significance of lipoprotein alterations caused by DAA therapy has not been explained yet. Moreover, DAA treatment of chronic hepatitis C improves hypertension control and atherosclerotic plaques. It is very likely that DAA therapeutic regimens will decrease both T2DM prevalence and cardiovascular risk in chronic hepatitis C patients; further research, however, is needed.
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Affiliation(s)
- Sylvia Drazilova
- Department of Internal Medicine, Hospital Poprad, Poprad, Slovakia
| | - Jakub Gazda
- 1st Department of Internal Medicine, PJ Safarik University, Faculty of Medicine and L Pasteur University Hospital, Kosice, Slovakia
| | - Martin Janicko
- 1st Department of Internal Medicine, PJ Safarik University, Faculty of Medicine and L Pasteur University Hospital, Kosice, Slovakia
| | - Peter Jarcuska
- 1st Department of Internal Medicine, PJ Safarik University, Faculty of Medicine and L Pasteur University Hospital, Kosice, Slovakia
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Correlation of CCR5 and NLRP3 gene polymorphisms with renal damage due to hepatitis C virus-related cryoglobulinemia. Exp Ther Med 2018; 16:3055-3059. [PMID: 30214525 PMCID: PMC6125838 DOI: 10.3892/etm.2018.6558] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Accepted: 07/18/2018] [Indexed: 12/30/2022] Open
Abstract
Correlation of C-C chemokine receptor type 5 (CCR5) and NACHT, LRR and PYD domain-containing protein 3 (NLRP3) gene polymorphisms with renal damage due to hepatitis C virus (HCV)-related cryoglobulinemia were investigated. The 1:1 matched case-control study design was adopted, 171 patients with renal damage due to HCV-related cryoglobulinemia were selected as the case group, and 171 patients without renal damage were selected as the control group. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis was used to detect the polymorphisms of locus rs1799987A/G in CCR5 gene and locus rs35829419A/C in NLRP3 gene of 171 pairs of HCV patients. SPSS 20.0 software was used for logistic regression analysis, and genetics package of the R programming language for Hardy-Weinberg equilibrium test. The frequencies of locus rs1799987A/G in CCR5 gene in the case group were 48.0 and 52.0%, while those in the control group were 47.9 and 52.1%; the frequencies of locus rs35829419A/C in NLRP3 gene were 55.8 and 44.2%, while those in the control group were 55.3 and 44.7%. The results of logistic regression analysis showed that the distribution of CCR5 gene polymorphism in the case group was statistically different from that in the control group (P<0.05), which had a statistical correlation with the renal damage due to HCV-related cryoglobulinemia (P<0.05). At rs1799987, GG genotype was compared with AA genotype, and AG genotype was compared with AA genotype; the results showed that the renal damage due to HCV-related cryoglobulinemia was not decreased [odds ratio (OR) = 0.91, 95% confidence interval (95% CI): 0.47–1.54; OR = 0.89, 95% CI: 0.49–1.31]. The negative analysis model of the GG genotype reduced the risk of renal damage due to HCV-related cryoglobulinemia remarkably (OR = 0.62, 95% CI: 0.39–0.98). Rs1799987A/G and gene polymorphism of CCR5 may be associated with renal damage due to HCV-related cryoglobulinemia, and the carriage of G allele may lower the incidence rate of the disease, while rs35829419A/C in NLRP3 has no correlation with renal damage due to HCV-related cryoglobulinemia.
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Orbital Pseudotumor as an Extrahepatic Complication of Chronic HCV Infection. Case Rep Infect Dis 2018; 2018:5498953. [PMID: 30002935 PMCID: PMC5998160 DOI: 10.1155/2018/5498953] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2017] [Accepted: 04/29/2018] [Indexed: 11/25/2022] Open
Abstract
We present a patient who was admitted for eye swelling, pain, and discharge, with CT orbits with contrast demonstrating inflammation and enlargement of the lacrimal glands and surrounding tissue. He was found to have an HCV infection for unknown duration upon further investigation. All other workup (autoimmune, rheumatic, and infectious) was unrevealing. The patient was diagnosed with orbital pseudotumor as an extrahepatic complication of chronic HCV infection, and he was managed with prednisone which dramatically decreased his eye swelling and pain. Steroid treatment may serve as a bridge to suppress symptoms of extrahepatic manifestations, especially in ocular cases, while HCV-infected patients await treatment to eradicate their HCV infection.
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Ruzicka DJ, Tetsuka J, Fujimoto G, Kanto T. Comorbidities and co-medications in populations with and without chronic hepatitis C virus infection in Japan between 2015 and 2016. BMC Infect Dis 2018; 18:237. [PMID: 29793436 PMCID: PMC5968711 DOI: 10.1186/s12879-018-3148-z] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2017] [Accepted: 05/15/2018] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Direct-acting anti-viral agents have improved the treatment of chronic hepatitis C virus (HCV) infection, but this treatment is challenging for patients using co-medications because of potential drug-drug interactions. This study aimed to examine the comorbidities and co-medications of Japanese chronic HCV patients by age group, compared with a non-HCV patient population. METHODS This was a retrospective observational study using a hospital-based medical claims database. We extracted data of patients with chronic HCV aged ≥18 years, and age-, sex-, and hospital-matched patients without HCV, for the period from January 2015 to November 2016, and then examined chronic comorbidities, long-term co-medications, and medications prescribed at least once during the study period. RESULTS We analysed data from 128,967 chronic HCV patients and 515,868 non-HCV patients. The median age was 70 years, and 51.0% of patients were male. More chronic HCV patients than non-HCV patients (70.5% vs. 47.1%) had at least one comorbidity, and older patients had more comorbidities than younger patients. The most common comorbidities in chronic HCV patients were diseases of oesophagus, stomach and duodenum (41.7%), followed by hypertensive diseases (31.4%). Chronic HCV patients used co-medications more commonly than non-HCV patients, and older patients used more co-medications. The most common long-term co-medications in chronic HCV patients were proton pump inhibitors (14.0%), which were prescribed to 31.9% of chronic HCV patients at least once during the study period. CONCLUSIONS Patients with chronic HCV in Japan had more comorbidities than patients without chronic HCV regardless of age. Particularly older patients, who constitute the majority of the HCV patient population in Japan, commonly had multiple comorbidities and used co-medications. To optimise HCV treatment, physicians need to know the exact medication profiles of patients and take appropriate action to manage drug-drug interactions.
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Affiliation(s)
- Daniel J. Ruzicka
- Medical Affairs, MSD K.K, Kitanomaru Square, 1-13-12 Kudan-kita, Chiyoda-ku, Tokyo 102-8667 Japan
| | - Jumpei Tetsuka
- Medical Affairs, MSD K.K, Kitanomaru Square, 1-13-12 Kudan-kita, Chiyoda-ku, Tokyo 102-8667 Japan
| | - Go Fujimoto
- Biostatistics and Research Decision Sciences, MSD K.K, Kitanomaru Square, 1-13-12 Kudan-kita, Chiyoda-ku, Tokyo 102-8667 Japan
| | - Tatsuya Kanto
- The Research Center for Hepatitis and Immunology Department of Liver Disease, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba 272-8516 Japan
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Vopálenský V, Khawaja A, Rožnovský L, Mrázek J, Mašek T, Pospíšek M. Characterization of Hepatitis C Virus IRES Quasispecies - From the Individual to the Pool. Front Microbiol 2018; 9:731. [PMID: 29740402 PMCID: PMC5928756 DOI: 10.3389/fmicb.2018.00731] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Accepted: 03/28/2018] [Indexed: 12/20/2022] Open
Abstract
Hepatitis C virus (HCV) is a single-stranded positive-sense RNA virus from the genus Hepacivirus. The viral genomic +RNA is 9.6 kb long and contains highly structured 5′ and 3′ untranslated regions (UTRs) and codes for a single large polyprotein, which is co- and post-translationally processed by viral and cellular proteases into at least 11 different polypeptides. Most of the 5′ UTR and an initial part of the polyprotein gene are occupied by an internal ribosome entry site (IRES), which mediates cap-independent translation of the viral proteins and allows the virus to overcome cellular antiviral defense based on the overall reduction of the cap-dependent translation initiation. We reconsidered published results concerning a search for possible correlation between patient response to interferon-based antiviral therapy and accumulation of nucleotide changes within the HCV IRES. However, we were unable to identify any such correlation. Rather than searching for individual mutations, we suggest to focus on determination of individual and collective activities of the HCV IRESs found in patient specimens. We developed a combined, fast, and undemanding approach based on high-throughput cloning of the HCV IRES species to a bicistronic plasmid followed by determination of the HCV IRES activity by flow cytometry. This approach can be adjusted for measurement of the individual HCV IRES activity and for estimation of the aggregate ability of the whole HCV population present in the specimen to synthesize viral proteins. To detect nucleotide variations in the individual IRESs, we used denaturing gradient gel electrophoresis (DGGE) analysis that greatly improved identification and classification of HCV IRES variants in the sample. We suggest that determination of the collective activity of the majority of HCV IRES variants present in one patient specimen in a given time represents possible functional relations among variant sequences within the complex population of viral quasispecies better than bare information about their nucleotide sequences. A similar approach might be used for monitoring of sequence variations in quasispecies populations of other RNA viruses in all cases when changes in primary sequence represent changes in measurable and easily quantifiable phenotypes.
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Affiliation(s)
- Václav Vopálenský
- Department of Genetics and Microbiology, Faculty of Science, Charles University, Prague, Czechia
| | - Anas Khawaja
- Department of Genetics and Microbiology, Faculty of Science, Charles University, Prague, Czechia
| | - Luděk Rožnovský
- Clinic of Infectious Medicine, University Hospital Ostrava, Ostrava, Czechia
| | - Jakub Mrázek
- Institute of Public Health in Ostrava, Ostrava, Czechia
| | - Tomáš Mašek
- Department of Genetics and Microbiology, Faculty of Science, Charles University, Prague, Czechia
| | - Martin Pospíšek
- Department of Genetics and Microbiology, Faculty of Science, Charles University, Prague, Czechia
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Hepatitis C virus infection and risk of Parkinson's disease: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2018; 30:9-13. [PMID: 29049127 DOI: 10.1097/meg.0000000000000991] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND/OBJECTIVE Hepatitis C virus (HCV) infection is one of the most common infections worldwide. Recent epidemiologic studies have suggested that patients with HCV infection might be at an increased risk of Parkinson's disease. However, the data on this relationship remain inconclusive. This meta-analysis was conducted with the aim to summarize all available evidence. PATIENTS AND METHODS A literature search was performed using MEDLINE and EMBASE database from inception to May 2017. Studies that reported relative risks, odd ratios (ORs), or hazard ratios comparing the risk of Parkinson's disease among HCV-infected patients versus participants without HCV infection were included. Pooled OR and 95% confidence interval were calculated using a random-effect, generic inverse variance method. RESULTS Of 468 studies, five studies with 323 974 participants met our eligibility criteria and were included in the analysis. We found a higher risk of Parkinson's disease among patients with chronic HCV infection compared with participants without HCV infection with the pooled OR of 1.35 (95% confidence interval: 1.19-1.52). The statistical heterogeneity of this study was insignificant (I=3%). The main limitation of this meta-analysis was the limited accuracy of diagnosis in the primary studies as they were coding-based studies. CONCLUSION This study demonstrated a higher risk of Parkinson's disease among HCV-infected patients. Further studies are required to clarify how this risk should be addressed in the clinical picture.
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Horiuchi Y, Lin J, Shinojima Y, Fujiwara K, Moriyama M, Nagase H. Characterizing key nucleotide polymorphisms of hepatitis C virus-disease associations via mass-spectrometric genotyping. Int J Oncol 2017; 52:441-452. [PMID: 29207078 DOI: 10.3892/ijo.2017.4209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Accepted: 10/16/2017] [Indexed: 11/06/2022] Open
Abstract
As more than 80% of hepatocellular carcinoma patients in Japan also suffer from hepatitis C virus infections some time in their medical history, identifying genetic aberrations associated to hepatitis C virulence in these individuals remains a high priority in the diagnosis and treatment of hepatocellular carcinoma. From the BioBank Japan Project, we acquired 480 subjects of hepatocellular carcinoma, chronic hepatitis and liver cirrhosis, and genotyped 131 clinically relevant host single nucleotide polymorphisms to survey the potential association between certain risk alleles and genes to a patient's predisposition to hepatitis C and liver cancer. Among those polymorphisms, we found 12 candidates with statistical significance to support association with hepatitis C virus susceptibility and genetic predisposition to hepatocellular carcinoma. SNPs in genes such as XPC, FANCA, KDR and BRCA2 also suggested likely connections between hepatitis C virus susceptibility and the contraction of liver diseases. Single nucleotide polymorphisms reported here provided suggestions for genes as biomarkers and elucidated insights briefing the linkage of hepatitis C virulence to the alteration of healthy liver genomic landscape as well as liver disease progression.
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Affiliation(s)
- Yuta Horiuchi
- Institute of Gastroenterology, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Jason Lin
- Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Chuo-ku, Chiba 260-8717, Japan
| | - Yui Shinojima
- Department of Cancer Genetics, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Kyoko Fujiwara
- Department of Cancer Genetics, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Mitsuhiko Moriyama
- Institute of Gastroenterology, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Hiroki Nagase
- Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Chuo-ku, Chiba 260-8717, Japan
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Abstract
More than 2 million Americans are infected with hepatitis C virus (HCV), and only about half are aware that they are infected. Primarily blood-borne, risk factors for the virus include injection or intranasal drug use, unregulated tattoos, incarceration, and blood transfusion before 1992. In addition, 75% of those with the virus were born between 1945 and 1965, thus making the baby-boomer cohort a population of screening interest. Because acute and early chronic HCV are often asymptomatic, screening of at-risk individuals is of utmost importance. Left untreated, HCV can go on to produce significant hepatic and extrahepatic manifestations.
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Affiliation(s)
- Dee Ann Bragg
- Via Christi Family Medicine Residency, University of Kansas School of Medicine (KUSM)-Wichita, 1121 South Clifton Street, Wichita, KS 67218, USA.
| | - Ashley Crowl
- University of Kansas School of Pharmacy, 1121 South Clifton Street, Wichita, KS 67218, USA
| | - Emily Manlove
- University of Kansas School of Medicine (KUSM)-Wichita, 1010 North Kansas Street, Wichita, KS 67214, USA
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Wu ZY, Li JR, Huang MH, Cheng JJ, Li H, Chen JH, Lv XQ, Peng ZG, Jiang JD. Internal driving factors leading to extrahepatic manifestation of the hepatitis C virus infection. Int J Mol Med 2017; 40:1792-1802. [PMID: 29039494 PMCID: PMC5716440 DOI: 10.3892/ijmm.2017.3175] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Accepted: 09/26/2017] [Indexed: 02/07/2023] Open
Abstract
The hepatitis C virus (HCV) infection is associated with various extrahepatic manifestations, which are correlated with poor outcomes, and thus increase the morbidity and mortality of chronic hepatitis C (CHC). Therefore, understanding the internal linkages between systemic manifestations and HCV infection is helpful for treatment of CHC. Yet, the mechanism by which the virus evokes the systemic diseases remains to be elucidated. In the present study, using gene set enrichment analysis (GSEA) and signaling pathway impact analysis (SPIA), a comprehensive analysis of microarray data of mRNAs was conducted in HCV-infected and -uninfected Huh7.5 cells, and signaling pathways (which are significantly activated or inhibited) and certain molecules (which are commonly important in those signaling pathways) were selected. Forty signaling pathways were selected using GSEA, and eight signaling pathways were selected with SPIA. These pathways are associated with cancer, metabolism, environmental information processing and organismal systems, which provide important information for further clarifying the intrinsic associations between syndromes of HCV infection, of which seven pathways were not previously reported, including basal transcription factors, pathogenic Escherichia coli infection, shigellosis, gastric acid secretion, dorso-ventral axis formation, amoebiasis and cholinergic synapse. Ten genes, SOS1, RAF1, IFNA2, IFNG, MTHFR, IGF1, CALM3, UBE2B, TP53 and BMP7 whose expression may be the key internal driving molecules, were selected using the online tool Anni 2.1. Furthermore, the present study demonstrated the internal linkages between systemic manifestations and HCV infection, and presented the potential molecules that are key to those linkages.
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Affiliation(s)
- Zhou-Yi Wu
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China
| | - Jian-Rui Li
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China
| | - Meng-Hao Huang
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China
| | - Jun-Jun Cheng
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China
| | - Hu Li
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China
| | - Jin-Hua Chen
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China
| | - Xiao-Qin Lv
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China
| | - Zong-Gen Peng
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China
| | - Jian-Dong Jiang
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China
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Hagymási K, Egresi A, Lengyel G. [Extrahepatic manifestations in chronic hepatitis C infected patients]. Orv Hetil 2017; 158:603-611. [PMID: 28415864 DOI: 10.1556/650.2017.30751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
The importance of chronic hepatitis C infection is significant. 3% of the World's population is infected. There is at least one extrahepatic manifestation in 50% of HCV patients, which makes the prognosis and mortality worse. The pathomechanisms included are cryoglobulin production, immunmechanisms, and direct viral effects. The authors summarize the main extrahepatic manifestations, as well as treatment possibilities. The aim is to draw attention to this colourful infection in order to improve the recognition in the era of the new effective direct antiviral agents. Orv. Hetil., 2017, 158(16), 603-612.
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Affiliation(s)
- Krisztina Hagymási
- II. Belgyógyászati Klinika, Semmelweis Egyetem, Általános Orvostudományi Kar Budapest, Szentkirályi u. 46., 1088
| | - Anna Egresi
- II. Belgyógyászati Klinika, Semmelweis Egyetem, Általános Orvostudományi Kar Budapest, Szentkirályi u. 46., 1088
| | - Gabriella Lengyel
- II. Belgyógyászati Klinika, Semmelweis Egyetem, Általános Orvostudományi Kar Budapest, Szentkirályi u. 46., 1088
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Zaily DG, Marlen CF, Santiago DC, Gillian MD, Carmen VS, Zurina CE, Enrique R. AS, Liz AL, Lisset GF, Sacha LDV, Elena FB. Clinical Evaluation of Terap C Vaccine in Combined Treatment with Interferon and Ribavirin in Patients with Hepatitis C. CURRENT THERAPEUTIC RESEARCH 2017; 85:20-28. [PMID: 29158855 PMCID: PMC5681293 DOI: 10.1016/j.curtheres.2017.04.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Accepted: 04/14/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND An estimated 170 million individuals worldwide are infected with the hepatitis C virus (HCV). Although treatment options using a combination of pegylated interferon and ribavirin (P-IFN/RBV) are available, sustained clearance of the virus is only achieved in approximately 40% of individuals infected with HCV genotype 1. Recent advances in the treatment of HCV using directly acting antiviral agents have been achieved; however, treatment can be very expensive and is associated with substantial side effects. The development of a new treatment modality is needed. One possible modality could be specific immunotherapy. Terap C is a therapeutic vaccine candidate composed of pIDKE2, a plasmid expressing HCV structural antigens, with a recombinant HCV core protein, Co.120. OBJECTIVE To assess the safety and efficacy of concomitant therapy with the candidate vaccine, Terap C, IFN α-2b and ribavirin in untreated individuals with HCV genotype 1 infection. METHODS This was a Phase II randomized, placebo-controlled, double-blind clinical trial evaluating the safety and efficacy of Terap C concomitant with IFN α-2b/RBV in 92 treatment-naïve patients with HCV genotype 1 infection. The study was conducted at the Gastroenterology Institute in Havana, Cuba. Patients were randomly assigned to 1 of 5 groups. The control group (Group 1) received IFN α-2b/RBV and placebo for 48 weeks. Groups 2 and 3 were administered Terap C 6 and 9 times, respectively, in addition to standard IFN α-2b/RBV treatment. In groups 4 and 5, Terap C was introduced 12 weeks after the initiation of IFN α-2b/RBV and administered 6 and 9 times, respectively, concomitant with IFN α-2b/RBV. RESULTS All patients showed some adverse events. Out of 3615 adverse events, only 18.8% were considered to be probably associated with administration of Terap C. Most events (47.4%) were considered to be improbably associated with of administration Terap C. Only 33.8% were considered possibly temporarily associated with Terap C, and can be explained by the use of conventional IFN α-2b + RBV or by HCV itself. The most common adverse events (≥65%) observed were pain at the injection site, headache, asthenia, psychiatric disturbances, fever, and gastrointestinal symptoms. Regarding sustained virological response, a 20% superiority was observed in the patients who received concomitant Terap C treatments from the beginning of the study compared with those who started after Week 12. CONCLUSIONS Vaccination with Terap C in patients with chronic HCV infection was safe and well tolerated. Clinical trial protocol code: IG/VHI/HC/0701; Public Register Code: RPCEC00000074.
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Pérez-Matute P, Oteo JA. Is it enough to eliminate hepatitis C virus to reverse the damage caused by the infection? World J Clin Infect Dis 2017; 7:1-5. [DOI: 10.5495/wjcid.v7.i1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2016] [Revised: 11/03/2016] [Accepted: 12/02/2016] [Indexed: 02/07/2023] Open
Abstract
Hepatitis C virus (HCV) infection represents one of the major causes of chronic liver disease, hepatocellular carcinoma and morbidity/mortality worldwide. It is also a major burden to the healthcare systems. A complete elimination of the HCV from the body through treatment is now possible. However, HCV not only alters the hepatic function. Several extra-hepatic manifestations are present in HCV-infected patients, which increase the mortality rate. Liver and gut are closely associated in what is called the “gut-liver axis”. A disrupted gut barrier leads to an increase in bacterial translocation and an activation of the mucosal immune system and secretion of inflammatory mediators that plays a key role in the progression of liver disease towards decompensated cirrhosis in HCV-infected patients. In addition, both qualitative and quantitative changes in the composition of the gut microbiota (GM) and states of chronic inflammation have been observed in patients with cirrhosis. Thus, a successful treatment of HCV infection should be also accompanied by a complete restoration of GM composition in order to avoid activation of the mucosal immune system, persistent inflammation and the development of long-term complications. Evaluation of GM composition after treatment could be of interest as a reliable indicator of the total or partial cure of these patients. However, studies focused on microbiota composition after HCV eradication from the body are lacking, which opens unique opportunities to deeply explore and investigate this exciting field.
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Menezes EG, Coelho-Dos-Reis JGA, Cardoso LM, Lopes-Ribeiro Á, Jonathan-Gonçalves J, Porto Gonçalves MT, Cambraia RD, Soares EB, Silva LD, Peruhype-Magalhães V, Rios M, Chancey C, Teixeira-Carvalho A, Martins-Filho OA, Teixeira R. Strategies for serum chemokine/cytokine assessment as biomarkers of therapeutic response in HCV patients as a prototype to monitor immunotherapy of infectious diseases. Antiviral Res 2017; 141:19-28. [PMID: 28163109 DOI: 10.1016/j.antiviral.2017.02.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Revised: 12/21/2016] [Accepted: 02/01/2017] [Indexed: 02/06/2023]
Abstract
In this study, strategies for serum biomarker assessment were developed for therapeutic monitoring of HCV patients. For this purpose, serum chemokine/cytokine levels were measured by cytometric-bead-array in HCV patients, categorized according to immunotherapy response as: non-responder/NR, relapser/REL and sustained-virologic-responder/SVR. The results demonstrated an overall increase of serum chemokine/cytokine levels in HCV patients. In general, therapeutic failure was associated with presence of a predominant baseline proinflammatory pattern with enhanced CCL5/RANTES, IFN-α, IFN-γ along with decreased IL-10 levels in NR and increased IL-6 and TNF in REL. SVR displayed lower baseline proinflammatory status with decreased CXCL8/IL-8, IL-12 and IL-17 levels. The inability to uphold IFN-α levels during immunotherapy was characteristic of NR. Serum chemokine/cytokine signatures further support the deleterious effect of proinflammatory baseline status and the critical role of increased/persistent IFN-α levels to guarantee the sustained virologic response. The prominent baseline proinflammatory milieu observed in NR and REL yielded a restricted biomarker network with small number of neighborhood connections, whereas SVR displayed a network with integrated cytokine connectivity. Noteworthy was that SVR presented a shift towards a proinflammatory pattern upon immunotherapy, assuming a pattern similar to that observed in NR and REL at baseline. Moreover, the immunotherapy guided REL towards a profile similar to SVR at baseline. Analysis of baseline-fold changes during treatment pointed out IFN-α and TNF as high-performance biomarkers to monitor immunotherapy outcome. This knowledge may contribute for novel insights into the treatment and control of the continuous public health threat posed by HCV infection worldwide.
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Affiliation(s)
- Erica Godinho Menezes
- Pós-graduação em Ciências Aplicadas à Saúde do Adulto, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Ambulatório de Hepatites Virais, Instituto Alfa de Gastroenterologia, Hospital das Clínicas/UFMG, Belo Horizonte, Minas Gerais, Brazil
| | | | - Ludmila Melo Cardoso
- Grupo Integrado de Pesquisa em Biomarcadores, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil
| | - Ágata Lopes-Ribeiro
- Grupo Integrado de Pesquisa em Biomarcadores, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil
| | - Juan Jonathan-Gonçalves
- Grupo Integrado de Pesquisa em Biomarcadores, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil
| | - Marco Túlio Porto Gonçalves
- Grupo Integrado de Pesquisa em Biomarcadores, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil
| | - Rodrigo Dias Cambraia
- Ambulatório de Hepatites Virais, Instituto Alfa de Gastroenterologia, Hospital das Clínicas/UFMG, Belo Horizonte, Minas Gerais, Brazil
| | - Eric Bassetti Soares
- Ambulatório de Hepatites Virais, Instituto Alfa de Gastroenterologia, Hospital das Clínicas/UFMG, Belo Horizonte, Minas Gerais, Brazil
| | - Luciana Diniz Silva
- Pós-graduação em Ciências Aplicadas à Saúde do Adulto, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Ambulatório de Hepatites Virais, Instituto Alfa de Gastroenterologia, Hospital das Clínicas/UFMG, Belo Horizonte, Minas Gerais, Brazil; Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Vanessa Peruhype-Magalhães
- Grupo Integrado de Pesquisa em Biomarcadores, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil
| | - Maria Rios
- Center for Biologics and Evaluation Research - US Food and Drug Administration, Silver Spring, MD, United States
| | - Caren Chancey
- Center for Biologics and Evaluation Research - US Food and Drug Administration, Silver Spring, MD, United States
| | - Andréa Teixeira-Carvalho
- Grupo Integrado de Pesquisa em Biomarcadores, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.
| | - Olindo Assis Martins-Filho
- Grupo Integrado de Pesquisa em Biomarcadores, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil
| | - Rosângela Teixeira
- Pós-graduação em Ciências Aplicadas à Saúde do Adulto, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Ambulatório de Hepatites Virais, Instituto Alfa de Gastroenterologia, Hospital das Clínicas/UFMG, Belo Horizonte, Minas Gerais, Brazil; Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
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Yang Y, Dang SS. Safety of direct antiviral agents for treatment of hepatitis C virus infection. Shijie Huaren Xiaohua Zazhi 2017; 25:659. [DOI: 10.11569/wcjd.v25.i8.659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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von Köckritz L, Dufour JF. Management of chronic hepatitis C in 2017. Hamostaseologie 2016; 37:186-195. [PMID: 27896359 DOI: 10.5482/hamo-16-07-0019] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2016] [Accepted: 11/04/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) represents one of the most common aetiologies of chronic liver disease and causes a major global health burden. Globally an estimated 80 million people are chronically infected, but the majority of whom is still undiagnosed. Prior to the discovery of the virus in 1989 a significant number of patients were exposed and consecutively infected with HCV via contaminated transfusions, as it is a blood-borne disease. Chronic HCV infection pursues a progressive course that ultimately results in the development of cirrhosis, liver failure and hepatocellular carcinoma (HCC), if left untreated. The efficiency and tolerability of therapeutical approaches improved considerably with the development of direct-acting antivirals (DAA). The majority of patients treated with the recommended DAA combinations can be cured, which is reflected in achievement of sustained virological response (SVR). This review is intended to provide guidance in the management of patients with chronic hepatitis C, including recommendations for adequate screening, diagnostic procedures, clinical care, treatment and follow-up strategies.
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Affiliation(s)
| | - Jean-François Dufour
- Prof. Dr. med. Jean-François Dufour, MD, Hepatology, University Clinic for Visceral Surgery and Medicine, Inselspital Bern, Freiburgstrasse, 3010 Bern, Switzerland, Phone: +41316328026; Fax: +41316327489, E-mail:
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