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Choudhary NS, Singh KA, Dhampalwar S, Saraf N. Acute Hepatitis C as an Acute Cause of Acute-on-chronic Liver Failure in Alcohol-associated Liver Disease. J Clin Exp Hepatol 2025; 15:102423. [PMID: 39553836 PMCID: PMC11567041 DOI: 10.1016/j.jceh.2024.102423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Accepted: 10/05/2024] [Indexed: 11/19/2024] Open
Affiliation(s)
- Narendra S. Choudhary
- Institute of Liver Transplantation and Regenerative Medicine, Medanta: The Medicity, Gurugram, Haryana, India
| | - Kunwar A. Singh
- Institute of Liver Transplantation and Regenerative Medicine, Medanta: The Medicity, Gurugram, Haryana, India
| | - Swapnil Dhampalwar
- Institute of Liver Transplantation and Regenerative Medicine, Medanta: The Medicity, Gurugram, Haryana, India
| | - Neeraj Saraf
- Institute of Liver Transplantation and Regenerative Medicine, Medanta: The Medicity, Gurugram, Haryana, India
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2
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Zou J, Li J, Wang X, Tang D, Chen R. Neuroimmune modulation in liver pathophysiology. J Neuroinflammation 2024; 21:188. [PMID: 39090741 PMCID: PMC11295927 DOI: 10.1186/s12974-024-03181-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 07/19/2024] [Indexed: 08/04/2024] Open
Abstract
The liver, the largest organ in the human body, plays a multifaceted role in digestion, coagulation, synthesis, metabolism, detoxification, and immune defense. Changes in liver function often coincide with disruptions in both the central and peripheral nervous systems. The intricate interplay between the nervous and immune systems is vital for maintaining tissue balance and combating diseases. Signaling molecules and pathways, including cytokines, inflammatory mediators, neuropeptides, neurotransmitters, chemoreceptors, and neural pathways, facilitate this complex communication. They establish feedback loops among diverse immune cell populations and the central, peripheral, sympathetic, parasympathetic, and enteric nervous systems within the liver. In this concise review, we provide an overview of the structural and compositional aspects of the hepatic neural and immune systems. We further explore the molecular mechanisms and pathways that govern neuroimmune communication, highlighting their significance in liver pathology. Finally, we summarize the current clinical implications of therapeutic approaches targeting neuroimmune interactions and present prospects for future research in this area.
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Affiliation(s)
- Ju Zou
- Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Jie Li
- Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Xiaoxu Wang
- Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Daolin Tang
- Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA
| | - Ruochan Chen
- Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
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Fiore V, Manca V, Colpani A, De Vito A, Maida I, Madeddu G, Babudieri S. Facing HCV as a Major Public Healthcare Threat in Italy: Epidemiology and Micro-Elimination Pathways among Underserved Populations. Healthcare (Basel) 2023; 11:2109. [PMID: 37510549 PMCID: PMC10379370 DOI: 10.3390/healthcare11142109] [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: 06/20/2023] [Revised: 07/18/2023] [Accepted: 07/21/2023] [Indexed: 07/30/2023] Open
Abstract
Underserved populations have a wide heterogeneity on healthcare provision and use. They also represent the key populations according to WHO 2030 goals for HCV micro-elimination. Our review evaluated the available literature on HCV diagnosis, staging, and treatment among underserved populations, such as incarcerated people, patients with psychiatric disorders, and migrants. A narrative review of literature was performed using key electronic databases (Scopus, Pubmed-MEDLINE) and search engines (Google Scholar). Peer-reviewed publications, grey literature on HCV, and recent models proposed for micro-elimination in underserved populations were included. An insight into the COVID-19 pandemic and its influence on HCV micro-elimination pathways will be also provided. Regarding prison settings, a progressive reduction in HCV epidemiology among incarcerated people in the last years was found (one-third of the level it had been before). People suffering from psychiatric disorders have a high anti-HCV prevalence, but there is a lack of data on active infections. A bidirectional relationship between HCV and psychiatric disorders was found. Migrants showed a very inconsistent assessment of HCV. Furthermore, available studies recorded data from populations with high heterogeneity of anti-HCV prevalence, Therefore, the reported results need caution in their evaluation.
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Affiliation(s)
- Vito Fiore
- Unit of Infectious and Tropical Diseases, Department of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, Italy
| | - Valentina Manca
- Unit of Infectious and Tropical Diseases, Department of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, Italy
| | - Agnese Colpani
- Unit of Infectious and Tropical Diseases, Department of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, Italy
| | - Andrea De Vito
- Unit of Infectious and Tropical Diseases, Department of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, Italy
| | - Ivana Maida
- Unit of Infectious and Tropical Diseases, Department of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, Italy
| | - Giordano Madeddu
- Unit of Infectious and Tropical Diseases, Department of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, Italy
| | - Sergio Babudieri
- Unit of Infectious and Tropical Diseases, Department of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, Italy
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Fiore V, De Vito A, Colpani A, Manca V, Maida I, Madeddu G, Babudieri S. Viral Hepatitis C New Microelimination Pathways Objective: Psychiatric Communities HCV Free. LIFE (BASEL, SWITZERLAND) 2022; 12:life12111873. [PMID: 36431008 PMCID: PMC9697639 DOI: 10.3390/life12111873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 11/08/2022] [Accepted: 11/11/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND People with psychiatric disorders have a high prevalence of HCV. For this reason, tailored interventions should be developed to reach this population. METHODS We performed a retrospective study on patients treated for HCV infection in psychiatric nursing homes, approached with a quick diagnosis, staging and treatment. RESULTS We included data on 586 people screened for HCV with quick tests. High HCV seroprevalence was found in this population (231; 39.4%). Among people who tested positive, there were high rates of active infection (220; 95.2%). Out of the 220 patients with active infection, 95.9% were male, 85.5% were Italian, median age was 43 (IQR = 35-52) years old. In the majority of cases (162; 73.6%), the risk factor was unknown. The most common genotype was 3a (98; 44.5%), and patients mostly had a low fibrosis, according with FIB-4 value (142; 64.5%). Of them, one (0.45%) categorically refused the treatment, and one (0.45%) had liver cirrhosis and advanced hepatocellular carcinoma. Overall, 218 patients underwent eligibility for DAAs. The most prescribed treatment was glecaprevir/pibrentasvir (GLE/PIB (172; 78.2%)). The others practiced sofosbuvir/velpatasvir (SOF/VEL). All patients reached the end of treatment. One (0.45%) was lost to follow up, and all the others reached the SVR12. CONCLUSIONS The point-of-care testing and pangenotypic DAAs' availability represent one of the most important steps for a fast diagnostic and therapeutical option. Tailored microelimination pathways for every difficult-to-reach/to-treat populations are needed. This would allow us to move more easily towards HCV elimination.
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McKay LGA, Thomas J, Albalawi W, Fattaccioli A, Dieu M, Ruggiero A, McKeating JA, Ball JK, Tarr AW, Renard P, Pollakis G, Paxton WA. The HCV Envelope Glycoprotein Down-Modulates NF-κB Signalling and Associates With Stimulation of the Host Endoplasmic Reticulum Stress Pathway. Front Immunol 2022; 13:831695. [PMID: 35371105 PMCID: PMC8964954 DOI: 10.3389/fimmu.2022.831695] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 02/21/2022] [Indexed: 11/13/2022] Open
Abstract
Following acute HCV infection, the virus establishes a chronic disease in the majority of patients whilst few individuals clear the infection spontaneously. The precise mechanisms that determine chronic HCV infection or spontaneous clearance are not completely understood but are proposed to be driven by host and viral genetic factors as well as HCV encoded immunomodulatory proteins. Using the HIV-1 LTR as a tool to measure NF-κB activity, we identified that the HCV E1E2 glycoproteins and more so the E2 protein down-modulates HIV-1 LTR activation in 293T, TZM-bl and the more physiologically relevant Huh7 liver derived cell line. We demonstrate this effect is specifically mediated through inhibiting NF-κB binding to the LTR and show that this effect was conserved for all HCV genotypes tested. Transcriptomic analysis of 293T cells expressing the HCV glycoproteins identified E1E2 mediated stimulation of the endoplasmic reticulum (ER) stress response pathway and upregulation of stress response genes such as ATF3. Through shRNA mediated inhibition of ATF3, one of the components, we observed that E1E2 mediated inhibitory effects on HIV-1 LTR activity was alleviated. Our in vitro studies demonstrate that HCV Env glycoprotein activates host ER Stress Pathways known to inhibit NF-κB activity. This has potential implications for understanding HCV induced immune activation as well as oncogenesis.
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Affiliation(s)
- Lindsay G. A. McKay
- Department of Clinical Infection, Microbiology and Immunology, Institute of Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
| | - Jordan Thomas
- Department of Clinical Infection, Microbiology and Immunology, Institute of Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
| | - Wejdan Albalawi
- Department of Clinical Infection, Microbiology and Immunology, Institute of Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
| | - Antoine Fattaccioli
- Laboratory of Biochemistry and Cell Biology (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur (UNamur), Namur, Belgium
| | - Marc Dieu
- MaSUN, Mass Spectrometry Facility, University of Namur (UNamur), Namur, Belgium
| | - Alessandra Ruggiero
- Department of Clinical Infection, Microbiology and Immunology, Institute of Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
| | - Jane A. McKeating
- Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Jonathan K. Ball
- Wolfson Centre for Global Virus Research and School of Life Sciences, University of Nottingham, Nottingham, United Kingdom
| | - Alexander W. Tarr
- Wolfson Centre for Global Virus Research and School of Life Sciences, University of Nottingham, Nottingham, United Kingdom
| | - Patricia Renard
- Laboratory of Biochemistry and Cell Biology (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur (UNamur), Namur, Belgium,MaSUN, Mass Spectrometry Facility, University of Namur (UNamur), Namur, Belgium
| | - Georgios Pollakis
- Department of Clinical Infection, Microbiology and Immunology, Institute of Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
| | - William A. Paxton
- Department of Clinical Infection, Microbiology and Immunology, Institute of Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom,*Correspondence: William A. Paxton,
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González Grande R, Santaella Leiva I, López Ortega S, Jiménez Pérez M. Present and future management of viral hepatitis. World J Gastroenterol 2021; 27:8081-8102. [PMID: 35068856 PMCID: PMC8704279 DOI: 10.3748/wjg.v27.i47.8081] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 04/08/2021] [Accepted: 12/07/2021] [Indexed: 02/06/2023] Open
Abstract
Viral hepatitis can result in important morbidity and mortality, with its impact on health conditioned by the specific type of hepatitis, the geographical region of presentation and the development and access to new drugs, among other factors. Most acute presentation forms are self-limiting and may even go unnoticed, with just a small percentage of cases leading to acute liver failure that may necessitate transplantation or even cause the death of the patient. However, when they become chronic, as in the case of hepatitis B virus and C virus, unless they are diagnosed and treated adequately they may have severe consequences, like cirrhosis or hepatocarcinoma. Understanding of the mechanisms of transmission, the pathogenesis, the presence of vaccinations and the development over recent years of new highly-efficient, potent drugs have meant that we are now faced with a new scenario in the management of viral hepatitis, particularly hepatitis B virus and hepatitis C virus. The spectacular advances in hepatitis C virus treatment have led the World Health Organization to propose the objective of its eradication by 2030. The key aspect to achieving this goal is to ensure that these treatments reach all the more vulnerable population groups, in whom the different types of viral hepatitis have a high prevalence and constitute a niche that may perpetuate infection and hinder its eradication. Accordingly, micro-elimination programs assume special relevance at the present time.
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Affiliation(s)
- Rocío González Grande
- UGC de Aparato Digestivo. Unidad de Hepatología-Trasplante Hepático, Hospital Regional Universitario de Málaga, Málaga 29010, Spain
| | - Inmaculada Santaella Leiva
- UGC de Aparato Digestivo. Unidad de Hepatología-Trasplante Hepático, Hospital Regional Universitario de Málaga, Málaga 29010, Spain
| | - Susana López Ortega
- UGC de Aparato Digestivo. Unidad de Hepatología-Trasplante Hepático, Hospital Regional Universitario de Málaga, Málaga 29010, Spain
| | - Miguel Jiménez Pérez
- UGC de Aparato Digestivo. Unidad de Hepatología-Trasplante Hepático, Hospital Regional Universitario de Málaga, Málaga 29010, Spain
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Coto-Llerena M, Lepore M, Spagnuolo J, Di Blasi D, Calabrese D, Suslov A, Bantug G, Duong FH, Terracciano LM, De Libero G, Heim MH. Interferon lambda 4 can directly activate human CD19 + B cells and CD8 + T cells. Life Sci Alliance 2021; 4:e201900612. [PMID: 33158978 PMCID: PMC7668538 DOI: 10.26508/lsa.201900612] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Revised: 10/26/2020] [Accepted: 10/26/2020] [Indexed: 12/12/2022] Open
Abstract
Compared with the ubiquitous expression of type I (IFNα and IFNβ) interferon receptors, type III (IFNλ) interferon receptors are mainly expressed in epithelial cells of mucosal barriers of the of the intestine and respiratory tract. Consequently, IFNλs are important for innate pathogen defense in the lung and intestine. IFNλs also determine the outcome of hepatitis C virus (HCV) infections, with IFNλ4 inhibiting spontaneous clearance of HCV. Because viral clearance is dependent on T cells, we explored if IFNλs can directly bind to and regulate human T cells. We found that human B cells and CD8+ T cells express the IFNλ receptor and respond to IFNλs, including IFNλ4. IFNλs were not inhibitors but weak stimulators of B- and T-cell responses. Furthermore, IFNλ4 showed neither synergistic nor antagonistic effects in co-stimulatory experiments with IFNλ1 or IFNα. Multidimensional flow cytometry of cells from liver biopsies of hepatitis patients from IFNλ4-producers showed accumulation of activated CD8+ T cells with a central memory-like phenotype. In contrast, CD8+ T cells with a senescent/exhausted phenotype were more abundant in IFNλ4-non-producers. It remains to be elucidated how IFNλ4 promotes CD8 T-cell responses and inhibits the host immunity to HCV infections.
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Affiliation(s)
- Mairene Coto-Llerena
- Department of Biomedicine, Hepatology, University Hospital and University of Basel, Basel, Switzerland
| | - Marco Lepore
- Department of Biomedicine, Experimental Immunology, University Hospital and University of Basel, Basel, Switzerland
| | - Julian Spagnuolo
- Department of Biomedicine, Experimental Immunology, University Hospital and University of Basel, Basel, Switzerland
| | - Daniela Di Blasi
- Department of Biomedicine, Hepatology, University Hospital and University of Basel, Basel, Switzerland
- Department of Biomedicine, Experimental Immunology, University Hospital and University of Basel, Basel, Switzerland
| | - Diego Calabrese
- Department of Biomedicine, Hepatology, University Hospital and University of Basel, Basel, Switzerland
| | - Aleksei Suslov
- Department of Biomedicine, Hepatology, University Hospital and University of Basel, Basel, Switzerland
| | - Glenn Bantug
- Department of Biomedicine, Immunobiology, University Hospital and University of Basel, Basel, Switzerland
| | - Francois Ht Duong
- Department of Biomedicine, Hepatology, University Hospital and University of Basel, Basel, Switzerland
| | - Luigi M Terracciano
- Molecular Pathology Division, Institute of Pathology, University Hospital Basel, Basel, Switzerland
| | - Gennaro De Libero
- Department of Biomedicine, Experimental Immunology, University Hospital and University of Basel, Basel, Switzerland
| | - Markus H Heim
- Department of Biomedicine, Hepatology, University Hospital and University of Basel, Basel, Switzerland
- Division of Gastroenterology and Hepatology, Clarunis, University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland
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Methanolic Extract of Teucrium Polium Exerts Immunomodulatory Properties in Human Peripheral Blood Mononuclear Cells. SERBIAN JOURNAL OF EXPERIMENTAL AND CLINICAL RESEARCH 2020. [DOI: 10.2478/sjecr-2020-0018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Abstract
Teucrium polium has been used in traditional medicine around the world for centuries in treatment of various conditions and diseases. Many studies have confirmed pharmacological effects of its extracts, although the immunomodulatory effect has not been investigated. Therefore, the aim of our study was to examine the immunomodulatory effect of methanolic extract of T. polium (TPE) on peripheral blood mononuclear cells (PBMCs) derived from healthy donors and patients with HCV infection. We analyzed the effect of the extract on PBMCs viability using the MTT test. The cell death type was determined using Annexin V-FITC/7-AAD staining. Immunophenotyping using anti-CD8 FITC, anti-CD4 PE, anti-CD3 ECD, anti-CD20 PC5, anti-CD14 FITC and anti-CD25 PC7 was performed by flow cytometry. Results of the MTT test indicate that TPE stimulates proliferation of healthy PBMCs, while the HCV PBMCs viability was slightly reduced.
The percentage of apoptotic HCV PBMCs was higher after TPE treatment compared to the control. The proportion of CD25-expressing cells was higher among the untreated HCV PBMCs than in the untreated healthy PBMCs. TPE treatment significantly and gradually increased CD25 expression in healthy PBMCs, whereas CD25 expression on HCV PBMCs increased only at the highest TPE concentration. The upregulation of double-positive CD3+CD25+, CD20+CD25+ and CD14+CD25+ cells was significant in TPE treated healthy PBMCs, while only the highest concentration was effective on HCV PBMCs. In summary, TPE exerts a strong immunomodulatory effect on healthy PBMCs and, only at the highest concentration, on HCV PBMNCs.
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Kardani K, Basimi P, Fekri M, Bolhassani A. Antiviral therapy for the sexually transmitted viruses: recent updates on vaccine development. Expert Rev Clin Pharmacol 2020; 13:1001-1046. [PMID: 32838584 DOI: 10.1080/17512433.2020.1814743] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION The sexually transmitted infections (STIs) caused by viruses including human T cell leukemia virus type-1 (HTLV-1), human immunodeficiency virus-1 (HIV-1), human simplex virus-2 (HSV-2), hepatitis C virus (HCV), hepatitis B virus (HBV), and human papillomavirus (HPV) are major public health issues. These infections can cause cancer or result in long-term health problems. Due to high prevalence of STIs, a safe and effective vaccine is required to overcome these fatal viruses. AREAS COVERED This review includes a comprehensive overview of the literatures relevant to vaccine development against the sexually transmitted viruses (STVs) using PubMed and Sciencedirect electronic search engines. Herein, we discuss the efforts directed toward development of effective vaccines using different laboratory animal models including mice, guinea pig or non-human primates in preclinical trials, and human in clinical trials with different phases. EXPERT OPINION There is no effective FDA approved vaccine against the sexually transmitted viruses (STVs) except for HBV and HPV as prophylactic vaccines. Many attempts are underway to develop vaccines against these viruses. There are several approaches for improving prophylactic or therapeutic vaccines such as heterologous prime/boost immunization, delivery system, administration route, adjuvants, etc. In this line, further studies can be helpful for understanding the immunobiology of STVs in human. Moreover, development of more relevant animal models is a worthy goal to induce effective immune responses in humans.
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Affiliation(s)
- Kimia Kardani
- Department of Hepatitis and AIDS, Pasteur Institute of Iran , Tehran, Iran
| | - Parya Basimi
- Department of Hepatitis and AIDS, Pasteur Institute of Iran , Tehran, Iran
| | - Mehrshad Fekri
- Department of Hepatitis and AIDS, Pasteur Institute of Iran , Tehran, Iran
| | - Azam Bolhassani
- Department of Hepatitis and AIDS, Pasteur Institute of Iran , Tehran, Iran
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Nanowire Aptamer-Sensitized Biosensor Chips with Gas Plasma-Treated Surface for the Detection of Hepatitis C Virus Core Antigen. COATINGS 2020. [DOI: 10.3390/coatings10080753] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Herein, we have demonstrated highly sensitive real-time biospecific detection of a protein marker of hepatitis C—the core antigen of hepatitis C virus (HCVcoreAg)—using a nanowire (NW) biosensor. The primary element of the NW-biosensor is a chip with p-type conductance, bearing silicon-on-insulator (SOI) nanowire structures on its surface. The nanowire structures are fabricated by gas-plasma treatment and electron beam lithography. The detection specificity was provided by sensitization of the sensor surface with aptamers against HCVcoreAg. The influence of buffer pH on the sensor response signal was studied. The effect of reverse polarity of the biosensor response signal with change from the acidic buffer pH to the neutral one was found. The lowest detectable HCVcoreAg concentration was determined to be 2.0 × 10−15 M in both acidic (pH 5.1) and neutral (pH 7.4) buffer solution. The proposed aptamer-sensitized sensor was also successfully applied to detect HCVcoreAg in serum samples of hepatitis C patients.
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Hatanaka T, Naganuma A, Tateyama Y, Yoshinari F, Hoshino T, Sato K, Hmwe SS, Aizaki H, Wakita T, Kakizaki S, Uraoka T. Ledipasvir and Sofosbuvir for Acute Hepatitis C Virus Monoinfection Associated with a High Risk of Acute Liver Failure. Intern Med 2019; 58:2969-2975. [PMID: 31243225 PMCID: PMC6859401 DOI: 10.2169/internalmedicine.2982-19] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
A 72-year-old Japanese man was referred to our hospital with yellow discoloration of the sclera and liver dysfunction. He was diagnosed with acute hepatitis C virus (HCV) infection on the basis of HCV-RNA positivity and anti-HCV seroconversion. A transjugular liver biopsy confirmed submassive hepatic necrosis. Five days after admission, no flapping tremor was observed, and the prothrombin time-international normalized ratio (PT-INR) and total bilirubin level showed increases of 1.70 and 17.8 mg/dL, respectively. The Model for End-Stage Liver Disease score was determined to be 25, and the risk of acute liver failure (ALF) was estimated to be 48% according to the Japan Hepatic Encephalopathy Prediction Model. Considering that rapid HCV clearance and temporary suppression of the immune response would prevent ALF, we prescribed oral ledipasvir (LDV) 90 mg and sofosbuvir (SOF) 400 mg for 12 weeks and intravenously injected methylprednisolone 1 g for 3 days. His PT-INR promptly improved, although the total bilirubin level increased to 30.3 mg/dL. Plasma bilirubin absorption was performed three times, and the total bilirubin level gradually decreased. HCV-RNA was still detectable at six weeks after the start of LDV/SOF therapy and finally undetectable at eight weeks. There were no adverse events associated with LDV/SOF. The patient was discharged 73 days after admission. A sustained virological response was achieved at 12 and 24 weeks after treatment. The findings from this case suggest that LDV/SOF therapy can be a promising option for acute HCV monoinfection associated with a high risk of ALF.
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Affiliation(s)
- Takeshi Hatanaka
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Japan
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Japan
| | - Atsushi Naganuma
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Japan
| | - Yumeo Tateyama
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Japan
| | - Fukiko Yoshinari
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Japan
| | - Takashi Hoshino
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Japan
| | - Ken Sato
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Japan
| | - Su Su Hmwe
- Department of Virology II, National Institute of Infectious Diseases, Japan
| | - Hideki Aizaki
- Department of Virology II, National Institute of Infectious Diseases, Japan
| | - Takaji Wakita
- Department of Virology II, National Institute of Infectious Diseases, Japan
| | - Satoru Kakizaki
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Japan
| | - Toshio Uraoka
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Japan
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Chernykh ER, Oleynik EA, Leplina OY, Starostina NM, Ostanin AA. Dendritic cells in the pathogenesis of viral hepatitis C. RUSSIAN JOURNAL OF INFECTION AND IMMUNITY 2019. [DOI: 10.15789/2220-7619-2019-2-239-252] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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13
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Irshad M, Gupta P, Irshad K. Immunopathogenesis of Liver Injury During Hepatitis C Virus Infection. Viral Immunol 2019; 32:112-120. [PMID: 30817236 DOI: 10.1089/vim.2018.0124] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The present report describes current concepts about the mechanism of liver cell injury caused by host immune response against hepatitis C virus (HCV) infection in human beings. This report is based on the observations from experimental studies and follow-up actions on human liver diseases. The results from different investigations suggest that liver injury depends on the presentation of viral antigen and the level of host immune response raised against HCV-related peptides. Both innate and adaptive immunity are triggered to counter the viral onset. During development of host immunity, the cell-mediated immune response involving CD4+ Th1 cells and CD8+ cytotoxic T-lymphocyte (CTL) cells were found to play a major role in causing liver damage. The hepatic Innate lymphoid cells (ILCs) subsets are involved in the immune regulation of different liver diseases: viral hepatitis, mechanical liver injury, and fibrosis. Humoral immunity and natural killer (NK) cell action also contributed in liver cell injury by antibody-dependent cellular cytotoxicity (ADCC). In fact, immunopathogenesis of HCV infection is a complex phenomenon where regulation of immune response at several steps decides the possibility of viral elimination or persistence. Regulation of immune response was noted starting from viral-host interaction to immune reaction cascade engaged in cell damage. The activation or suppression of interferon-stimulated genes, NK cell action, CTL inducement by regulatory T cells (Treg), B cell proliferation, and so on was demonstrated during HCV infection. Involvement of HLA in antigen presentation, as well as types of viral genotypes, also influenced host immune response against HCV peptides. The combined effect of all these effector mechanisms ultimately decides the progression of viral onset to acute or chronic infection. In conclusion, immunopathogenesis of liver injury after HCV infection may be ascribed mainly to host immune response. Second, it is cell-mediated immunity that plays a predominant role in liver cell damage.
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Affiliation(s)
- Mohammad Irshad
- 1 Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Priyanka Gupta
- 2 Clinical Biochemistry Division, Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Khushboo Irshad
- 3 Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
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Hepatitis C Infection in Hemodialysis Patients. CURRENT HEALTH SCIENCES JOURNAL 2019; 44:107-112. [PMID: 30746156 PMCID: PMC6320456 DOI: 10.12865/chsj.44.02.02] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Accepted: 03/27/2018] [Indexed: 01/01/2023]
Abstract
Three centuries after the identification of hepatitis C virus (HCV), specialized literature has outlined the epidemiology, viral kinetics and clinical manifestations of this infection. A major cause of morbidity-mortality in patients with renal transplantation and in hemodialysis patients is HCV infection. In high seroprevalence countries, internal accounts are not uniform. The European trend is to decrease the incidence and prevalence of HCV in hemodialysis patients. In Europe, the prevalence of HCV infection among hemodialysis patients tends to be higher than that of the general population, but it is variable by region. Some studies indicate a decrease in incidence in parallel with prevalence in dialysis centers over the last 10 years, while others maintain a high incidence. In some countries, as is the case with Romania, both prevalence and incidence remain high, with the major route of transmission being nosocomial, probably due to limited resources for a rapidly growing dialyzed population. Some authors recommend more isolation measures to be taken in centers with high prevalence of infection.
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15
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Fouchard-Hubert I. L’hépatite C, un enjeu majeur de santé publique. ACTUALITES PHARMACEUTIQUES 2019. [DOI: 10.1016/j.actpha.2018.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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16
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Virlogeux V, Berthillon P, Bordes I, Larrat S, Crouy S, Scholtès C, Pradat P, Maynard M, Zoulim F, Leroy V, Chemin I, Trépo C, Petit MA. Anti-E1E2 antibodies status prior therapy favors direct-acting antiviral treatment efficacy. Clin Res Hepatol Gastroenterol 2018; 42:313-318. [PMID: 29551607 DOI: 10.1016/j.clinre.2018.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2017] [Revised: 01/18/2018] [Accepted: 02/13/2018] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Presence of anti-E1E2 antibodies was previously associated with spontaneous cure of hepatitis C virus (HCV) and predictive before treatment of a sustained virological response (SVR) to bi- or tri-therapy in naïve or experienced patients, regardless of HCV genotype. We investigated the impact of anti-E1E2 seroprevalence at baseline on treatment response in patients receiving direct-acting antiviral (DAA) therapy. MATERIAL AND METHODS We screened anti-E1E2 antibodies by ELISA in serum samples collected at treatment initiation for two groups of patients: 59 with SVR at the end of DAA treatment and 44 relapsers after DAA treatment. Nineteen patients received a combination of ribavirin (RBV) or PEG-interferon/ribavirin with sofosbuvir or daclatasvir and others received interferon-free treatment with DAA±RBV. HCV viral load was measured at different time points during treatment in a subgroup of patients. RESULTS A significant association was observed between presence of anti-E1E2 and HCV viral load<6log10 prior treatment. Among patients with anti-E1E2 at baseline, 70% achieved SVR whereas among patients without anti-E1E2, only 45% achieved SVR. Conversely, 66% of patients experiencing DAA-failure were anti-E1E2 negative at baseline. In the multivariate analysis, presence of anti-E1E2 was significantly associated with SVR after adjustment on potential cofounders such as age, sex, fibrosis stage, prior HCV treatment and alanine aminotransferase (ALT) level. CONCLUSIONS The presence of anti-E1E2 at treatment initiation is a predictive factor of SVR among patients treated with DAA and more likely among patients with low initial HCV viral load (<6log10). Absence of anti-E1E2 at baseline could predict DAA-treatment failure.
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Affiliation(s)
- Victor Virlogeux
- Centre de recherche en cancérologie de Lyon (CRCL), UMR Inserm 1052/CNRS 5286, 69003 Lyon, France; Université Claude-Bernard-Lyon 1, 69008 Lyon, France; Service d'hépato-gastroentérologie, hôpital de la Croix-Rousse, hospices civils de Lyon, 69004 Lyon, France
| | - Pascale Berthillon
- Centre de recherche en cancérologie de Lyon (CRCL), UMR Inserm 1052/CNRS 5286, 69003 Lyon, France; Université Claude-Bernard-Lyon 1, 69008 Lyon, France
| | - Isabelle Bordes
- Centre de recherche en cancérologie de Lyon (CRCL), UMR Inserm 1052/CNRS 5286, 69003 Lyon, France; Université Claude-Bernard-Lyon 1, 69008 Lyon, France
| | - Sylvie Larrat
- Laboratoire de virologie, institut de biologie et pathologie, CHU Grenoble-Alpes, 38043 Grenoble cedex 9, France
| | - Stéphanie Crouy
- Centre de recherche en cancérologie de Lyon (CRCL), UMR Inserm 1052/CNRS 5286, 69003 Lyon, France; Université Claude-Bernard-Lyon 1, 69008 Lyon, France; Service d'hépato-gastroentérologie, hôpital de la Croix-Rousse, hospices civils de Lyon, 69004 Lyon, France
| | - Caroline Scholtès
- Centre de recherche en cancérologie de Lyon (CRCL), UMR Inserm 1052/CNRS 5286, 69003 Lyon, France; Université Claude-Bernard-Lyon 1, 69008 Lyon, France; Service d'hépato-gastroentérologie, hôpital de la Croix-Rousse, hospices civils de Lyon, 69004 Lyon, France
| | - Pierre Pradat
- Centre de recherche en cancérologie de Lyon (CRCL), UMR Inserm 1052/CNRS 5286, 69003 Lyon, France; Université Claude-Bernard-Lyon 1, 69008 Lyon, France; Service d'hépato-gastroentérologie, hôpital de la Croix-Rousse, hospices civils de Lyon, 69004 Lyon, France
| | - Marianne Maynard
- Centre de recherche en cancérologie de Lyon (CRCL), UMR Inserm 1052/CNRS 5286, 69003 Lyon, France; Université Claude-Bernard-Lyon 1, 69008 Lyon, France; Service d'hépato-gastroentérologie, hôpital de la Croix-Rousse, hospices civils de Lyon, 69004 Lyon, France
| | - Fabien Zoulim
- Centre de recherche en cancérologie de Lyon (CRCL), UMR Inserm 1052/CNRS 5286, 69003 Lyon, France; Université Claude-Bernard-Lyon 1, 69008 Lyon, France; Service d'hépato-gastroentérologie, hôpital de la Croix-Rousse, hospices civils de Lyon, 69004 Lyon, France
| | - Vincent Leroy
- Service d'hépato-gastroentérologie, CHU Grenoble-Alpes, 38043 Grenoble cedex 9, France
| | - Isabelle Chemin
- Centre de recherche en cancérologie de Lyon (CRCL), UMR Inserm 1052/CNRS 5286, 69003 Lyon, France; Université Claude-Bernard-Lyon 1, 69008 Lyon, France
| | - Christian Trépo
- Centre de recherche en cancérologie de Lyon (CRCL), UMR Inserm 1052/CNRS 5286, 69003 Lyon, France; Université Claude-Bernard-Lyon 1, 69008 Lyon, France; Service d'hépato-gastroentérologie, hôpital de la Croix-Rousse, hospices civils de Lyon, 69004 Lyon, France
| | - Marie-Anne Petit
- Centre de recherche en cancérologie de Lyon (CRCL), UMR Inserm 1052/CNRS 5286, 69003 Lyon, France; Université Claude-Bernard-Lyon 1, 69008 Lyon, France.
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Brook G, Brockmeyer N, van de Laar T, Schellberg S, Winter AJ. 2017 European guideline for the screening, prevention and initial management of hepatitis B and C infections in sexual health settings. Int J STD AIDS 2018; 29:949-967. [PMID: 29716442 DOI: 10.1177/0956462418767576] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
This guideline updates the 2010 European guideline for the management of hepatitis B and C virus infections. It is primarily intended to provide advice on testing, prevention and initial management of viral hepatitis B and C for clinicians working in sexual health clinical settings in European countries. The guideline is in a new question and answer format based on clinical situations, from which population/intervention/comparison/outcome questions were formulated. Updates cover areas such as epidemiology, point-of-care tests for hepatitis B, hepatitis C risk and 'chemsex', and HIV pre-exposure prophylaxis and hepatitis B. We have also included a short paragraph on hepatitis E noting there is no evidence for sexual transmission. The guideline has been prepared in accordance with the Europe protocol for production available at http://www.iusti.org/regions/europe/pdf/2017/ProtocolForProduction2017.pdf.
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Affiliation(s)
- Gary Brook
- 1 Genitourinary Medicine, London North West Healthcare NHS Trust, London, UK
| | - Norbert Brockmeyer
- 2 Klinik für Dermatologie, Venerologie und Allergologie, Ruhr-Universität Bochum, Bochum, Germany
| | - Thijs van de Laar
- 3 Department of Bloodborne Infections, Sanquin Blood Supply, Amsterdam, Netherlands
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18
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Ravens S, Hengst J, Schlapphoff V, Deterding K, Dhingra A, Schultze-Florey C, Koenecke C, Cornberg M, Wedemeyer H, Prinz I. Human γδ T Cell Receptor Repertoires in Peripheral Blood Remain Stable Despite Clearance of Persistent Hepatitis C Virus Infection by Direct-Acting Antiviral Drug Therapy. Front Immunol 2018; 9:510. [PMID: 29616028 PMCID: PMC5864898 DOI: 10.3389/fimmu.2018.00510] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 02/26/2018] [Indexed: 12/28/2022] Open
Abstract
Human γδ T cells can contribute to clearance of hepatitis C virus (HCV) infection but also mediate liver inflammation. This study aimed to understand the clonal distribution of γδ T cells in peripheral blood of chronic HCV patients and following HCV clearance by interferon-free direct-acting antiviral drug therapies. To this end, γδ T cell receptor (TCR) repertoires were monitored by mRNA-based next-generation sequencing. While the percentage of Vγ9+ T cells was higher in patients with elevated liver enzymes and a few expanded Vδ3 clones could be identified in peripheral blood of 23 HCV-infected non-cirrhotic patients, overall clonality and complexity of γδ TCR repertoires were largely comparable to those of matched healthy donors. Monitoring eight chronic HCV patients before, during and up to 1 year after therapy revealed that direct-acting antiviral (DAA) drug therapies induced only minor alterations of TRG and TRD repertoires of Vγ9+ and Vγ9- cells. Together, we show that peripheral γδ TCR repertoires display a high stability (1) by chronic HCV infection in the absence of liver cirrhosis and (2) by HCV clearance in the course of DAA drug therapy.
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Affiliation(s)
- Sarina Ravens
- Institute of Immunology, Hannover Medical School, Hannover, Germany
| | - Julia Hengst
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Verena Schlapphoff
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Katja Deterding
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Akshay Dhingra
- Institute of Virology, Hannover Medical School, Hannover, Germany
| | - Christian Schultze-Florey
- Institute of Immunology, Hannover Medical School, Hannover, Germany.,Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
| | - Christian Koenecke
- Institute of Immunology, Hannover Medical School, Hannover, Germany.,Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,Department of Gastroenterology and Hepatology, Essen University Hospital, Essen, Germany
| | - Immo Prinz
- Institute of Immunology, Hannover Medical School, Hannover, Germany
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19
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Hamdy M, Kassim SK, Khairy E, Maher M, Mansour KA, Albreedy AM. Ghrelin gene polymorphism as a genetic biomarker for prediction of therapy induced clearance in Egyptian chronic HCV patients. Gene 2018; 649:74-79. [PMID: 29374597 DOI: 10.1016/j.gene.2018.01.077] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2017] [Revised: 01/06/2018] [Accepted: 01/23/2018] [Indexed: 12/14/2022]
Abstract
Ghrelin (GHRL) has important implications for liver disease. It has anti-inflammatory effects, regulates cell proliferation, modulates the fibrogenic response and protects liver tissue. Genetic variations in the GHRL gene may play a crucial role in the development of chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Therefore, we examined the association of GHRL gene polymorphisms (rs26312 and rs27647), and its serum level to virologic responses to combined sofosbuvir and Simeprevir therapy for a course of 12 successive weeks in Egyptian chronic hepatitis C (CHC) patients. METHODS Human genomic and clinical data were collected from 100 Egyptian participants in this study, 90 HCV patients who received sofosbuvir and Simeprevir and 10 non-HCV healthy subjects. Genotyping of GHRL rs26312 and rs27647, were determined with the TaqMan qRT-PCR allele detection assay. The serum GHRL concentrations were determined using enzyme-linked immunosorbent assay (ELISA). RESULTS GHRL polymorphisms (rs26312 and rs27647) genotype distributions and allele frequencies did not differ between HCV patients and normal healthy subjects or between patient groups when compared according to the therapeutic response. In addition, we found significant lower serum GHRL levels in CHC patients compared with the healthy controls. However, there was no significant association of the GHRL rs26312 and rs27647 polymorphisms with GHRL levels in CHC patients. We conclude that GHRL SNPs (rs26312 and rs27647) do not affect response to combined sofosbuvir and Simeprevir treatment in chronic Egyptian HCV patients.
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Affiliation(s)
- Marwa Hamdy
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, Egypt, P.O. box 11381
| | - Samar Kamal Kassim
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, Egypt, P.O. box 11381
| | - Eman Khairy
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, Egypt, P.O. box 11381.
| | - Mohsen Maher
- General Medicine Department, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, Egypt
| | - Khaled Amr Mansour
- General Medicine Department, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, Egypt
| | - Ashraf M Albreedy
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, Egypt
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20
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Gaeta GB, Puoti M, Coppola N, Santantonio T, Bruno R, Chirianni A, Galli M. Treatment of acute hepatitis C: recommendations from an expert panel of the Italian Society of Infectious and Tropical Diseases. Infection 2017; 46:183-188. [PMID: 29238918 DOI: 10.1007/s15010-017-1107-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2017] [Accepted: 12/04/2017] [Indexed: 12/24/2022]
Abstract
AIM This paper is aimed at providing practical recommendations for the management of acute hepatitis C (AHC). METHODS This is an expert position paper based on the literature revision. Final recommendations were graded by level of evidence and strength of the recommendations. RESULTS Treatment of AHC with direct-acting antivirals (DAA) is safe and effective; it overcomes the limitations of INF-based treatments. CONCLUSIONS Early treatment with DAA should be offered when available.
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Affiliation(s)
- Giovanni B Gaeta
- Infectious Diseases, Campania University "Luigi Vanvitelli", Naples, Italy.
| | - Massimo Puoti
- Infectious Diseases, Niguarda Hospital, Milan, Italy
| | - Nicola Coppola
- Infectious Diseases, Campania University "Luigi Vanvitelli", Naples, Italy
| | | | | | | | - Massimo Galli
- Infectious Diseases, University of Milan, Milan, Italy
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21
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Tsai WL, Chang TH, Sun WC, Chan HH, Wu CC, Hsu PI, Cheng JS, Yu ML. Metformin activates type I interferon signaling against HCV via activation of adenosine monophosphate-activated protein kinase. Oncotarget 2017; 8:91928-91937. [PMID: 29190886 PMCID: PMC5696152 DOI: 10.18632/oncotarget.20248] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Accepted: 07/12/2017] [Indexed: 12/25/2022] Open
Abstract
Activation of the type I interferon (IFN) signaling pathway is essential for the eradication of hepatitis C virus (HCV). Metformin can activate adenosine monophosphate-activated protein kinase (AMPK) to reduce insulin resistance. Cross talks between AMPK and IFN signaling remain unclear. To understand the influence of metformin on the type I IFN signaling pathway and HCV infection, the full-length HCV replicon OR6 cells and the infectious HCV clones JFH1 were used to assess the anti-HCV effect of the insulin sensitizers, metformin and pioglitazone. Immunofluorescence staining and the immunoblotting of HCV viral protein demonstrated that metformin, but not pioglitazone, inhibited HCV replication in OR-6 and JFH-1-infected Huh 7.5.1 cells. Immunoblotting data showed that metformin activated the phosphorylation of STAT-1 and STAT-2 in OR-6 and JFH-1 infected Huh 7.5.1 cells. Metformin enhanced the phosphorylation of AMPK, and the metformin-activated IFN signaling was down-regulated by AMPK inhibitor. After treatment of AMPK inhibitor, the level of HCV core protein decreased by metformin can be rescued. In conclusion, metformin activates type I interferon signaling and inhibits the replication of HCV via activation of AMPK.
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Affiliation(s)
- Wei-Lun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Tsung-Hsien Chang
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,Department of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan
| | - Wei-Chi Sun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Hoi-Hung Chan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Chun-Ching Wu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Ping-I Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Jin-Shiung Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.,Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
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22
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Squires JE, Balistreri WF. Hepatitis C virus infection in children and adolescents. Hepatol Commun 2017; 1:87-98. [PMID: 29404447 PMCID: PMC5721428 DOI: 10.1002/hep4.1028] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Revised: 02/17/2017] [Accepted: 02/22/2017] [Indexed: 12/11/2022] Open
Affiliation(s)
- James E Squires
- Division of Gastroenterology, Hepatology, and Nutrition Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center Pittsburgh PA
| | - William F Balistreri
- Division of Gastroenterology Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine Cincinnati OH
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23
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Li BJ, He Y, Zhang Y, Guo YH, Zhou Y, Zhang PX, Wang W, Zhao JR, Li JG, Zuo WZ, Fan C, Jia ZS. Interferon-α-induced CD100 on naïve CD8 + T cells enhances antiviral responses to hepatitis C infection through CD72 signal transduction. J Int Med Res 2017; 45:89-100. [PMID: 28222623 PMCID: PMC5536608 DOI: 10.1177/0300060516676136] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Objectives We investigated the effects of CD100 on naïve CD8+ T cells during hepatitis C virus (HCV) infection after interferon-α (IFN-α) therapy to clarify the mechanism underlying the effect of IFN-α in enhancing the antiviral response. Methods The CD100 molecules on subsets of CD8+ T cells were analysed with flow cytometry. The effects of CD100-overexpressing naïve CD8+ T cells were determined with ELISAs and an MTT cytotoxicity assay. The role of CD100-CD72 signal transduction was analysed with a neutralization and transwell assays. Results HCV infection reduced CD100 expression on CD8+ T cells, whereas IFN-α treatment significantly increased CD100 expression on naïve CD8+ T cells. The increased CD100 interacted with the CD72 receptor and enhanced PBMC cytokine secretion (IFN-γ and tumour necrosis factor-α) and cytotoxicity. Conclusions IFN-α-induced CD100 on naïve CD8+ T cells promotes PBMC cytokine secretion and cytotoxicity through CD100-CD72 signalling during HCV infection.
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Affiliation(s)
- Bing Jie Li
- 2 First Affiliated Hospital, School of Medicine, Shihezi University, Xinjiang, China
| | - Yu He
- 1 Department of Infectious Diseases and Center of Liver Diseases, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China
| | - Ying Zhang
- 1 Department of Infectious Diseases and Center of Liver Diseases, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China
| | - Yong Hong Guo
- 1 Department of Infectious Diseases and Center of Liver Diseases, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China
| | - Yun Zhou
- 1 Department of Infectious Diseases and Center of Liver Diseases, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China
| | - Pei Xin Zhang
- 1 Department of Infectious Diseases and Center of Liver Diseases, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China
| | - Wei Wang
- 1 Department of Infectious Diseases and Center of Liver Diseases, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China
| | - Jie Ru Zhao
- 1 Department of Infectious Diseases and Center of Liver Diseases, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China
| | - Jin Ge Li
- 1 Department of Infectious Diseases and Center of Liver Diseases, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China
| | - Wei Ze Zuo
- 2 First Affiliated Hospital, School of Medicine, Shihezi University, Xinjiang, China
| | - Chao Fan
- 1 Department of Infectious Diseases and Center of Liver Diseases, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China
| | - Zhan Sheng Jia
- 1 Department of Infectious Diseases and Center of Liver Diseases, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China
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24
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Dirchwolf M, Marciano S, Mauro E, Ruf AE, Rezzonico L, Anders M, Chiodi D, Petta NG, Borzi S, Tanno F, Ridruejo E, Barreyro F, Shulman C, Plaza P, Carbonetti R, Tadey L, Schroder T, Fainboim H. Clinical epidemiology of acute hepatitis C in South America. J Med Virol 2016; 89:276-283. [PMID: 27253181 DOI: 10.1002/jmv.24588] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/31/2016] [Indexed: 12/14/2022]
Abstract
There is scarce data pertaining to acute hepatitis C (aHC) infection in South America. We aimed to describe clinical characteristics and evolution of aHC in a South American cohort. A retrospective survey was conducted at 13 hepatology units. All patients ≥16 years old with aHC diagnosis were included. Demographic, clinical and outcome information were registered in a standardized ad hoc questionnaire. Sixty-four patients were included. The majority were middle-aged (median age: 46 years) and female (65.6%); most of them were symptomatic at diagnosis (79.6%). HCV-1 was the most prevalent genotype (69.2%). Five patients had liver failure: three cases of severe acute hepatitis, one case of fulminant hepatitis and one case of acute-on-chronic liver failure. Nosocomial exposure was the most prevalent risk factor. Evolution was assessed in 46 patients. In the untreated cohort, spontaneous resolution occurred in 45.8% and was associated with higher values of AST/ALT and with the absence of intermittent HCV RNA viremia (P = 0.01, 0.05, and 0.01, respectively). In the treated cohort, sustained virological response was associated with nosocomial transmission and early treatment initiation (P = 0.04 each). The prevalence of nosocomial transmission in this South-American cohort of aHC stresses the importance of following universal precautions to prevent HCV infection. J. Med. Virol. 89:276-283, 2017. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Melisa Dirchwolf
- Hepatopatías Infecciosas, Hospital F.J. Muñiz, Buenos Aires, Argentina
| | | | - Ezequiel Mauro
- Liver Unit, Hospital Italiano de Buenos, Buenos Aires, Argentina
| | - Andrés Eduardo Ruf
- Fundación para la Docencia e Investigación de las Enfermedades del Hígado (FUNDIEH), Buenos Aires, Argentina
| | - Lucrecia Rezzonico
- Hepatología, Hospital de la Asociación Médica Dr. Felipe Glasman, Bahía Blanca, Buenos Aires, Argentina
| | - Margarita Anders
- Unidad de Hepatología y Trasplante Hepático, Hospital Alemán, Buenos Aires, Argentina
| | - Daniela Chiodi
- Hospital de Clínicas, Facultad de Medicina, UDELAR, Montevideo, Uruguay
| | - Néstor Gill Petta
- Servicio de Gastroenterología y Hepatología, Hospital Central del Instituto de Previsión Social de Asunción, Paraguay
| | - Silvia Borzi
- Sección Hepatología, HIGA Prof. Dr. Rodolfo Rossi, La Plata Buenos Aires, Argentina
| | - Federico Tanno
- Servicio de Hepatología y Gastroenterología, Hospital Provincial del Centenario de Rosario, Argentina
| | - Ezequiel Ridruejo
- Sección Hepatología, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno "CEMIC", Unidad de Hepatología y Trasplante Hepático, Hospital Universitario Austral, Buenos Aires, Argentina
| | - Fernando Barreyro
- Laboratorio de Microbiología, Facultad de Química y Ciencias Naturales Universidad de Misiones, Posadas, Argentina
| | | | - Pablo Plaza
- Gastroenterología y Hepatología, Salta Capital, Argentina
| | - Rodolfo Carbonetti
- Gastroenterología y Hepatología, Hospital de Clínicas Nicolás Avellaneda, Tucumán, Argentina
| | - Luciana Tadey
- Unidad de Virología, Hospital F.J. Muñiz, Buenos Aires, Argentina
| | - Teresa Schroder
- Hepatopatías Infecciosas, Hospital F.J. Muñiz, Buenos Aires, Argentina
| | - Hugo Fainboim
- Hepatopatías Infecciosas, Hospital F.J. Muñiz, Buenos Aires, Argentina
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Heim MH, Bochud PY, George J. Host - hepatitis C viral interactions: The role of genetics. J Hepatol 2016; 65:S22-S32. [PMID: 27641986 DOI: 10.1016/j.jhep.2016.07.037] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Revised: 07/29/2016] [Accepted: 07/29/2016] [Indexed: 12/15/2022]
Abstract
Hepatitis C virus (HCV) is a major cause of chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma. Only a minority of patients can clear the virus spontaneously. Elimination of HCV during acute infection correlates with a rapid induction of innate, especially interferon (IFN)-induced genes, and a delayed induction of adaptive immune responses. There is a strong association between genetic variants in the IFNλ (IL28B) locus with the rate of spontaneous clearance. Individuals with the ancestral IFNλ4 allele capable of producing a fully active IFNλ4 are paradoxically not able to clear HCV in the acute phase and develop chronic hepatitis C (CHC) with more than 90% probability. In the chronic phase of HCV infection, the wild-type IFNλ4 genotype is strongly associated with an induction of hundreds of classical type I/type III IFN stimulated genes in hepatocytes. However, the activation of the endogenous IFN system in the liver is ineffective in clearing HCV, and is even associated with impaired therapeutic responses to pegylated (Peg)IFNα containing treatments. While the role of genetic variation in the IFNλ locus to the outcome of CHC treatment has declined, it is clear that variation not only at this locus, but also at other loci, modulate clinically important liver phenotypes, including inflammation, fibrosis progression and the development of hepatocellular cancer. In this review, we summarize current knowledge about the role of genetics in the host response to viral hepatitis and the potential future evolution of knowledge in understanding host-viral interactions.
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Affiliation(s)
- Markus H Heim
- Division of Gastroenterology and Hepatology, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland; Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
| | - Pierre-Yves Bochud
- Infectious Diseases Service, University Hospital and University of Lausanne, Rue du Bugnon 46, 1011 Lausanne-CHUV, Switzerland.
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, NSW, Australia.
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Ferns RB, Tarr AW, Hue S, Urbanowicz RA, McClure CP, Gilson R, Ball JK, Nastouli E, Garson JA, Pillay D. Hepatitis C virus quasispecies and pseudotype analysis from acute infection to chronicity in HIV-1 co-infected individuals. Virology 2016; 492:213-24. [PMID: 26971243 DOI: 10.1016/j.virol.2016.02.003] [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: 11/10/2015] [Revised: 01/14/2016] [Accepted: 02/05/2016] [Indexed: 01/01/2023]
Abstract
HIV-1 infected patients who acquire HCV infection have higher rates of chronicity and liver disease progression than patients with HCV mono-infection. Understanding early events in this pathogenic process is important. We applied single genome sequencing of the E1 to NS3 regions and viral pseudotype neutralization assays to explore the consequences of viral quasispecies evolution from pre-seroconversion to chronicity in four co-infected individuals (mean follow up 566 days). We observed that one to three founder viruses were transmitted. Relatively low viral sequence diversity, possibly related to an impaired immune response, due to HIV infection was observed in three patients. However, the fourth patient, after an early purifying selection displayed increasing E2 sequence evolution, possibly related to being on suppressive antiretroviral therapy. Viral pseudotypes generated from HCV variants showed relative resistance to neutralization by autologous plasma but not to plasma collected from later time points, confirming ongoing virus escape from antibody neutralization.
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Affiliation(s)
- R Bridget Ferns
- Division of Infection & Immunity, Faculty of Medical Sciences, University College London, United Kingdom; Clinical Microbiology & Virology, UCL Hospital NHS Foundation Trust, United Kingdom.
| | - Alexander W Tarr
- School of Life Sciences & NIHR Biomedical Research Unit in Gastrointestinal & Liver Diseases, Faculty of Medicine and Health Sciences, University of Nottingham, United Kingdom
| | - Stephane Hue
- Division of Infection & Immunity, Faculty of Medical Sciences, University College London, United Kingdom
| | - Richard A Urbanowicz
- School of Life Sciences & NIHR Biomedical Research Unit in Gastrointestinal & Liver Diseases, Faculty of Medicine and Health Sciences, University of Nottingham, United Kingdom
| | - C Patrick McClure
- School of Life Sciences & NIHR Biomedical Research Unit in Gastrointestinal & Liver Diseases, Faculty of Medicine and Health Sciences, University of Nottingham, United Kingdom
| | - Richard Gilson
- Research Department of Infection and Population Health, University College London, United Kingdom
| | - Jonathan K Ball
- School of Life Sciences & NIHR Biomedical Research Unit in Gastrointestinal & Liver Diseases, Faculty of Medicine and Health Sciences, University of Nottingham, United Kingdom
| | - Eleni Nastouli
- Clinical Microbiology & Virology, UCL Hospital NHS Foundation Trust, United Kingdom
| | - Jeremy A Garson
- Division of Infection & Immunity, Faculty of Medical Sciences, University College London, United Kingdom
| | - Deenan Pillay
- Division of Infection & Immunity, Faculty of Medical Sciences, University College London, United Kingdom; Wellcome Trust Africa Centre for Health and Population Sciences, University of KwaZulu, Natal, South Africa
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Network Analysis of the Chronic Hepatitis C Virome Defines Hypervariable Region 1 Evolutionary Phenotypes in the Context of Humoral Immune Responses. J Virol 2015; 90:3318-29. [PMID: 26719263 DOI: 10.1128/jvi.02995-15] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2015] [Accepted: 12/22/2015] [Indexed: 02/06/2023] Open
Abstract
UNLABELLED Hypervariable region 1 (HVR1) of hepatitis C virus (HCV) comprises the first 27 N-terminal amino acid residues of E2. It is classically seen as the most heterogeneous region of the HCV genome. In this study, we assessed HVR1 evolution by using ultradeep pyrosequencing for a cohort of treatment-naive, chronically infected patients over a short, 16-week period. Organization of the sequence set into connected components that represented single nucleotide substitution events revealed a network dominated by highly connected, centrally positioned master sequences. HVR1 phenotypes were observed to be under strong purifying (stationary) and strong positive (antigenic drift) selection pressures, which were coincident with advancing patient age and cirrhosis of the liver. It followed that stationary viromes were dominated by a single HVR1 variant surrounded by minor variants comprised from conservative single amino acid substitution events. We present evidence to suggest that neutralization antibody efficacy was diminished for stationary-virome HVR1 variants. Our results identify the HVR1 network structure during chronic infection as the preferential dominance of a single variant within a narrow sequence space. IMPORTANCE HCV infection is often asymptomatic, and chronic infection is generally well established in advance of initial diagnosis and subsequent treatment. HVR1 can undergo rapid sequence evolution during acute infection, and the variant pool is typically seen to diverge away from ancestral sequences as infection progresses from the acute to the chronic phase. In this report, we describe HVR1 viromes in chronically infected patients that are defined by a dominant epitope located centrally within a narrow variant pool. Our findings suggest that weakened humoral immune activity, as a consequence of persistent chronic infection, allows for the acquisition and maintenance of host-specific adaptive mutations at HVR1 that reflect virus fitness.
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Abdel-Ghaffar TY, Sira MM, El Naghi S. Hepatitis C genotype 4: The past, present, and future. World J Hepatol 2015; 7:2792-2810. [PMID: 26668691 PMCID: PMC4670951 DOI: 10.4254/wjh.v7.i28.2792] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2015] [Revised: 08/02/2015] [Accepted: 11/25/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) genotype (GT) 4 represents 12%-15% (15-18 million) of total global HCV infection. It is prevalent in Northern and Equatorial Africa and the Middle East, and is also present in some countries in Europe. GT-4 (and subtype 4a in particular) dominates the HCV epidemic in Egypt. In underdeveloped countries, risk factors associated with HCV infection may be due to unsafe medical practices or other factors such as familial transmission, mother’s HCV status, or illiteracy. HCV prevention and control programs should include health education, increased community awareness towards the disease, controlling infection distribution in health-care centers, proper sterilization of medical and dental instruments, and ensuring safe supply of blood and blood-products. Response rates to a 48-wk combined pegylated-interferon (PEG-IFN) and ribavirin (RBV) treatment range from 40%-69%, and HCV-GT-4 has been considered better than GT-1 but worse than GT-2 and GT-3 in treatment with PEG-IFN/RBV. However, with the introduction of the HCV-GT-1 effective protease inhibitors boceprevir and telaprevir in 2011, HCV-GT-4 became the “most difficult (GT) to treat”. Recently, the direct-acting antivirals (DAAs) with pan- genotypic activities simeprevir, sofosbuvir, and daclatasvir have been recommended in triple regimens with PEG-IFN/RBV for the treatment of HCV-GT-4. An IFN-free regimen will be available for treatment of all genotypes of HCV in the near future. To date, several DAAs have been developed and are currently being evaluated in various combinations in clinical trials. As new regimens and new agents are being approved by the Food and Drug Administration, we can expect the guidelines for HCV treatment to be changed. The availability of shorter, simpler, and more tolerable treatment regimens can reduce the morbidity and mortality associated with HCV infection. With such a large number of therapeutic agents available, we can end up with a range of choices that we can select from to treat patients.
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Ksiaa Cheikhrouhou L, Lakhoua-Gorgi Y, Sfar I, Jendoubi-Ayed S, Aouadi H, Makhlouf M, Ayed K, Ben Abdallah T. Natural evolution of hepatitis C virus infection in hemodialysis Tunisian patients and CTLA-4 SNP's. World J Gastroenterol 2015; 21:10150-10158. [PMID: 26401079 PMCID: PMC4572795 DOI: 10.3748/wjg.v21.i35.10150] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Revised: 04/01/2015] [Accepted: 06/10/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To analyze the polymorphisms of CTLA-4 gene involved in the response against hepatitis C virus (HCV) infection.
METHODS: We recruited 500 hemodialysed patients from several hemodialysis centers, all HCV-antibody positive, spread over different regions of Tunisia, as part of a national survey in 2008 conducted in the laboratory of immunology at the Charles Nicolle hospital Tunisia, classified into two groups G1 (PCR+) and G2 (PCR-) according to the presence or absence of viral RNA. Of these patients, 307 were followed prospectively on a viral molecular level over a period from 2002 to 2008, divided into two groups based on the persistence and viral clearance. PCR-RFLP was performed for the analysis of SNPs (+49) A/G and (+6230) G/A CTLA-4 for these 500 patients and 358 healthy controls.
RESULTS: Analysis of clinical and virological characteristics of our cohort suggests a nosocomial infection in our hemodialysed patients with transfusion history as a primary risk factor and a predominance of genotype 1b. The haplotype analysis revealed an increase of frequencies of GG (+49)/(CT60) CTLA-4 in the entire patients group compared to controls (P = 0.0036 and OR = 1.42; 95%CI: 1.12-1.79, respectively). This haplotype is therefore associated with susceptibility to HCV infection.
CONCLUSION: Our study suggests a possible role of CTLA-4 polymorphisms in the outcome of HCV infection in the Tunisian hemodialysed population.
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Economic, organizational and budget impact of a new diagnostic plan for HCV detection: what’s “new”? ACTA ACUST UNITED AC 2015. [DOI: 10.1007/s13631-015-0098-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
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Marinaki S, Boletis JN, Sakellariou S, Delladetsima IK. Hepatitis C in hemodialysis patients. World J Hepatol 2015; 7:548-558. [PMID: 25848478 PMCID: PMC4381177 DOI: 10.4254/wjh.v7.i3.548] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2014] [Revised: 12/10/2014] [Accepted: 12/31/2014] [Indexed: 02/06/2023] Open
Abstract
Despite reduction of hepatitis C prevalence after recognition of the virus and testing of blood products, hemodialysis (HD) patients still comprise a high risk group. The natural history of hepatitis C virus (HCV) infection in dialysis is not fully understood while the clinical outcome differs from that of the general population. HD patients show a milder liver disease with lower aminotransferase and viral levels depicted by milder histological features on liver biopsy. Furthermore, the “silent” clinical course is consistent with a slower disease progression and a lower frequency of cirrhosis and hepatocellular carcinoma. Potential explanations for the “beneficial” impact of uremia and hemodialysis on chronic HCV infection are impaired immunosurveillance leading to a less aggressive host response to the virus and intradialytic release of “hepatoprotective” cytokines such as interferon (IFN)-α and hepatocyte growth factor. However, chronic hepatitis C is associated with a higher liver disease related cardiovascular and all-cause mortality of HD patients. Therapy is indicated in selected patients groups including younger patients with low comorbidity burden and especially renal transplant candidates, preferably after performance of a liver biopsy. According to current recommendations, choice of treatment is IFN or pegylated interferon with a reported sustained viral response at 30%-40% and a withdrawal rate ranging from 17% to 30%. New data regarding combination therapy with low doses of ribavirin which provide higher standard variable rates and good safety results, offer another therapeutic option. The new protease inhibitors may be the future for HCV infected HD patients, though data are still lacking.
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Pfaender S, Cavalleri JMV, Walter S, Doerrbecker J, Campana B, Brown RJP, Burbelo PD, Postel A, Hahn K, Anggakusuma, Riebesehl N, Baumgärtner W, Becher P, Heim MH, Pietschmann T, Feige K, Steinmann E. Clinical course of infection and viral tissue tropism of hepatitis C virus-like nonprimate hepaciviruses in horses. Hepatology 2015; 61:447-59. [PMID: 25212983 DOI: 10.1002/hep.27440] [Citation(s) in RCA: 105] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2014] [Accepted: 09/10/2014] [Indexed: 12/14/2022]
Abstract
UNLABELLED Hepatitis C virus (HCV) has a very narrow species and tissue tropism and efficiently replicates only in humans and the chimpanzee. Recently, several studies identified close relatives to HCV in different animal species. Among these novel viruses, the nonprimate hepaciviruses (NPHV) that infect horses are the closest relatives of HCV described to date. In this study, we analyzed the NPHV prevalence in northern Germany and characterized the clinical course of infection and viral tissue tropism to explore the relevance of HCV-related horse viruses as a model for HCV infection. We found that approximately 31.4% of 433 horses were seropositive for antibodies (Abs) against NPHV and approximately 2.5% carried viral RNA. Liver function analyses revealed no indication for hepatic impairment in 7 of 11 horses. However, serum gamma-glutamyl transferase (GGT) concentrations were mildly elevated in 3 horses, and 1 horse displayed even highly elevated GGT levels. Furthermore, we observed that NPHV infection could be cleared in individual horses with a simultaneous emergence of nonstructural (NS)3-specific Abs and transient elevation of serum levels of liver-specific enzymes indicative for a hepatic inflammation. In other individual horses, chronic infections could be observed with the copresence of viral RNA and NS3-specific Abs for over 6 months. For the determination of viral tissue tropism, we analyzed different organs and tissues of 1 NPHV-positive horse using quantitative real-time polymerase chain reaction and fluorescent in situ hydridization and detected NPHV RNA mainly in the liver and at lower amounts in other organs. CONCLUSION Similar to HCV infections in humans, this work demonstrates acute and chronic stages of NPHV infection in horses with viral RNA detectable predominantly within the liver.
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Affiliation(s)
- Stephanie Pfaender
- Institute for Experimental Virology, TWINCORE Center for Experimental and Clinical Infection Research Hannover, Germany
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Terczyńska-Dyla E, Bibert S, Duong FHT, Krol I, Jørgensen S, Collinet E, Kutalik Z, Aubert V, Cerny A, Kaiser L, Malinverni R, Mangia A, Moradpour D, Müllhaupt B, Negro F, Santoro R, Semela D, Semmo N, Heim MH, Bochud PY, Hartmann R. Reduced IFNλ4 activity is associated with improved HCV clearance and reduced expression of interferon-stimulated genes. Nat Commun 2014; 5:5699. [DOI: 10.1038/ncomms6699] [Citation(s) in RCA: 108] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2014] [Accepted: 10/28/2014] [Indexed: 02/08/2023] Open
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Heim MH, Thimme R. Innate and adaptive immune responses in HCV infections. J Hepatol 2014; 61:S14-25. [PMID: 25443342 DOI: 10.1016/j.jhep.2014.06.035] [Citation(s) in RCA: 205] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2014] [Revised: 06/29/2014] [Accepted: 06/30/2014] [Indexed: 12/21/2022]
Abstract
Hepatitis C virus has been identified a quarter of a decade ago as a leading cause of chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma. Only a minority of patients can clear the virus spontaneously during acute infection. Elimination of HCV during acute infection correlates with a rapid induction of innate, especially interferon (IFN) induced genes, and a delayed induction of adaptive immune responses. However, the majority of patients is unable to clear the virus and develops viral persistence in face of an ongoing innate and adaptive immune response. The virus has developed several strategies to escape these immune responses. For example, to escape innate immunity, the HCV NS3/4A protease can efficiently cleave and inactivate two important signalling molecules in the sensory pathways that react to HCV pathogen-associated molecular patterns (PAMPs) to induce IFNs, i.e., the mitochondrial anti-viral signalling protein (MAVS) and the Toll-IL-1 receptor-domain-containing adaptor-inducing IFN-β (TRIF). Despite these escape mechanisms, IFN-stimulated genes (ISGs) are induced in a large proportion of patients with chronic infection. Of note, chronically HCV infected patients with constitutive IFN-stimulated gene (ISG) expression have a poor response to treatment with pegylated IFN-α (PegIFN-α) and ribavirin. The mechanisms that protect HCV from IFN-mediated innate immune reactions are not entirely understood, but might involve blockade of ISG protein translation at the ribosome, localization of viral replication to cell compartments that are not accessible to anti-viral IFN-stimulated effector systems, or direct antagonism of effector systems by viral proteins. Escape from adaptive immune responses can be achieved by emergence of viral escape mutations that avoid recognition by antibodies and T cells. In addition, chronic infection is characterized by the presence of functionally and phenotypically altered NK and T cell responses that are unable to clear the virus but most likely contribute to the ongoing liver disease. In this review, we will summarize current knowledge about the role of innate and adaptive immune responses in determining the outcome of HCV infection.
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Affiliation(s)
- Markus H Heim
- Division of Gastroenterology and Hepatology, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland; Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
| | - Robert Thimme
- Department of Medicine, Clinic for Gastroenterology, Hepatology, Endocrinology, Infectious Diseases, University Hospital Freiburg, Freiburg, Germany.
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Choudhary MC, Gupta E, Pandey P, Natarajan V, Sharma S, Vashishtha C, Sharma MK, Kazim SN, Sarin SK. Identification and full-length molecular characterization of rare hepatitis C virus genotype 5a from India. Arch Virol 2014; 160:329-33. [PMID: 25193070 DOI: 10.1007/s00705-014-2220-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Accepted: 08/28/2014] [Indexed: 12/13/2022]
Abstract
This report presents a molecular characterization of the complete genome of a rare hepatitis C virus (HCV) genotype (GT5a) from India. Sequence homology of full genome revealed that the strain belonged to HCV GT5a. To trace the origin of this virus and to understand its evolutionary pattern, a phylogenetic reconstruction was carried out on full HCV genome sequences using Bayesian coalescent methods. The phylogenetic tree reconstruction revealed genotypic divergence, with formation of distinct clades. This analysis revealed that HCV genotype 5 might have originated from HCV genotype 3, as they have a recent common ancestor.
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Affiliation(s)
- Manish Chandra Choudhary
- Department of Research, Institute of Liver and Biliary Sciences (ILBS), Vasant Kunj, New Delhi, 110070, India
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Fernández Rodriguez CM, Gutierrez Garcia ML. [Impact of antiviral therapy on the natural history of hepatitis C virus]. GASTROENTEROLOGIA Y HEPATOLOGIA 2014; 37:583-92. [PMID: 25066318 DOI: 10.1016/j.gastrohep.2014.05.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2014] [Accepted: 05/28/2014] [Indexed: 02/08/2023]
Abstract
Chronic hepatitis C virus infection affects around 150 million persons, and 350,000 persons worldwide die of this disease each year. Although the data on its natural history are incomplete, after the acute infection, most patients develop chronic forms of hepatitis C with variable stages of fibrosis. In these patients, continual inflammatory activity can cause significant fibrosis, cirrhosis, decompensation of the liver disease, or hepatocarcinoma. In the next few years, it is expected that hepatitis C virus infection and its complications will significantly increase, as will the incidence of hepatocarcinoma in Spain. This review presents the data on the natural history of hepatitis C virus infection and discusses the potential impact of antiviral therapy on the distinct stages of the disease.
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KASL clinical practice guidelines: management of hepatitis C. Clin Mol Hepatol 2014; 20:89-136. [PMID: 25032178 PMCID: PMC4099340 DOI: 10.3350/cmh.2014.20.2.89] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2014] [Accepted: 05/20/2014] [Indexed: 12/16/2022] Open
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Santantonio T, Fasano M, Sagnelli E, Tundo P, Babudieri S, Fabris P, Toti M, Di Perri G, Marino N, Pizzigallo E, Angarano G. Acute hepatitis C: a 24-week course of pegylated interferon α-2b versus a 12-week course of pegylated interferon α-2b alone or with ribavirin. Hepatology 2014; 59:2101-9. [PMID: 24442928 DOI: 10.1002/hep.26991] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2013] [Revised: 11/19/2013] [Accepted: 12/23/2013] [Indexed: 01/01/2023]
Abstract
UNLABELLED Therapy of acute hepatitis C (AHC) has not yet been standardized and several issues are still unresolved. This open, randomized, multicenter trial aimed to assess the efficacy and safety of a 24-week course of pegylated IFN (Peg-IFN) alpha-2b versus a 12-week course of Peg-IFN alpha-2b alone or with ribavirin (RBV) in AHC patients. One hundred and thirty HCV acutely infected patients who did not spontaneously resolve by week 12 after onset were consecutively enrolled and randomized to receive Peg-IFN alpha-2b monotherapy (1.5 μg/kg/week) for 24 or 12 weeks (arm 1, n = 44 and arm 2, n = 43, respectively) or in combination with RBV (10.6 mg/kg/day) for 12 weeks (arm 3, n = 43). The primary endpoint was undetectable HCV RNA at 6-month posttreatment follow-up (sustained virological response; SVR). All patients were followed for 48 weeks after therapy cessation. HCV RNA levels were determined by real-time polymerase chain reaction (limit of detection: 15 IU/mL) at the central laboratory at baseline, week 4, end of treatment, and 6 and 12 months posttreatment. Using an intent-to-treat analysis, overall SVR rate was 71.5%. In particular, an SVR was achieved in 31 of 44 (70.5%), 31 of 43 (72.1%), and 31 of 43 (72.1%) patients in arms 1, 2, and 3, respectively (P = 0.898). Sixteen patients (12.3%) prematurely discontinued therapy or were lost to follow-up; thus, sustained response rates with per-protocol analysis were 81.6%, 81.6%, and 81.6% for patients in arms 1, 2, and 3 respectively. With multivariate analysis, virologic response at week 4 of treatment was an independent predictor of SVR. Peg-IFN alpha-2b was well tolerated. CONCLUSION Peg-IFN alpha-2b induces a high SVR in chronically evolving AHC patients. Response rates were not influenced by combination therapy or treatment duration.
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Sagnelli E, Santantonio T, Coppola N, Fasano M, Pisaturo M, Sagnelli C. Acute hepatitis C: clinical and laboratory diagnosis, course of the disease, treatment. Infection 2014; 42:601-10. [PMID: 24619833 DOI: 10.1007/s15010-014-0608-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Accepted: 02/24/2014] [Indexed: 02/06/2023]
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Abstract
A 42-year-old woman developed epigastric abdominal pain and acutely elevated serum transaminase levels during a course of chemotherapy for breast cancer. Serum antibodies to hepatitis A, B and C were not identified initially, but subsequently a high hepatitis C viral load was detected. Ultrasonic imaging of the liver was normal. Serum transaminase elevations resolved within 2 months, and, after 6 months without therapy, the hepatitis C viral load became undetectable.
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Affiliation(s)
- Allison Venner
- Division of Gastroenterology and Hepatology, 1 University of New Mexico, MSC10-5550, Albuquerque, NM, 87131, USA,
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EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol 2014; 60:392-420. [PMID: 24331294 DOI: 10.1016/j.jhep.2013.11.003] [Citation(s) in RCA: 646] [Impact Index Per Article: 58.7] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2013] [Accepted: 11/05/2013] [Indexed: 02/06/2023]
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Kil H, Jeong SH, Kim JW, Byoun YS, Min BY, Woo BH, Lee YJ, Kim YS. Role of interleukin-28B genetic polymorphisms in Korean patients with hepatitis C virus infection. Gut Liver 2014; 8:70-8. [PMID: 24516704 PMCID: PMC3916691 DOI: 10.5009/gnl.2014.8.1.70] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2013] [Revised: 04/27/2013] [Accepted: 05/22/2013] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND/AIMS This study investigated the role of single nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B) gene with respect to clinical outcomes and the antiviral response in hepatitis C virus (HCV) infection to suggest the practical utility of IL28B genotyping in Korea. METHODS Two SNPs near IL28B, rs12979860 and rs8099917, were analyzed using an allelic discrimination assay in a total of 454 individuals, including 147 health-check examinees and 307 patients with HCV infection. RESULTS The CC genotype frequency was significantly higher in the spontaneous recovery group than in the chronic infection group and was higher in the chronic hepatitis group than in the liver cirrhosis or hepatocellular carcinoma group, suggesting its favorable role in the clinical outcome. Multivariate analysis revealed that the rs12979860 CC genotype was an independent predictor of sustained virologic response (SVR) in genotype 1 HCV infection. During the currently used response-guided therapy, IL28B genotyping was most helpful for the patients who exhibit early virologic responses without rapid virologic responses, as those patients exhibiting the non-CC type did not achieve SVR, although they represented approximately one-third of the total patients. CONCLUSIONS The IL28B SNP is an independent predictor of SVR. Our results may be helpful if the findings are carefully applied to select patients in Korea.
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Affiliation(s)
- Ho Kil
- 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
| | - Jin-Wook Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Young Sang Byoun
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Bo Young Min
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Byung-Hyun Woo
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Youn Jae Lee
- Department of Internal Medicine, Inje University Busan Baik Hospital, Inje University College of Medicine, Busan, Korea
| | - Young Seok Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea
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El-Shabrawi MH, Kamal NM. Burden of pediatric hepatitis C. World J Gastroenterol 2013; 19:7880-7888. [PMID: 24307782 PMCID: PMC3848136 DOI: 10.3748/wjg.v19.i44.7880] [Citation(s) in RCA: 85] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2013] [Revised: 09/24/2013] [Accepted: 11/05/2013] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) is a major health burden infecting 170-210 million people worldwide. Additional 3-4 millions are newly-infected annually. Prevalence of pediatric infection varies from 0.05%-0.36% in the United States and Europe; up to 1.8%-5.8% in some developing countries. The highest prevalence occurs in Egypt, sub-Saharan Africa, Amazon basin and Mongolia. HCV has been present in some populations for several centuries, notably genotypes 1 and 2 in West Africa. Parenteral anti-schistosomal therapy practiced in the 1960s until the early 1980s had spread HCV infection throughout Egypt. Parenteral acquisition of HCV remains a major route for infection among Egyptian children. Insufficient screening of transfusions, unsterilized injection equipment and re-used needles and syringes continue to be major routes of HCV transmission in developing countries, whereas vertical transmission and adolescent high-risk behaviors (e.g., injection drug abuse) are the major routes in developed countries. The risk of vertical transmission from an infected mother to her unborn/newborn infant is approximately 5%. Early stages of HCV infection in children do not lead to marked impairment in the quality of life nor to cognitive, behavioral or emotional dysfunction; however, caregiver stress and family system strain may occur. HCV slowly progresses to serious complications as cirrhosis (1%-2%) and hepatocellular carcinoma (HCC) especially in the presence of risk factors as hemolytic anemias, obesity, treated malignancy, and concomitant human immune deficiency and/or hepatitis B virus co-infection. HCV vaccine remains elusive to date. Understanding the immune mechanisms in patients who successfully cleared the infection is essential for vaccine development. The pediatric standard of care treatment consists of pegylated interferon-α 2a or b plus ribavirin for 24-48 wk. The new oral direct acting antivirals, approved for adults, need further evaluation in children. Sustained virologic response varies depending on the viral load, genotype, duration of infection, degree of aminotransferase elevation, adiposity and single nucleotide polymorphisms of interleukin (IL)-28B locus. The goals of treatment in individual patients are virus eradication, prevention of cirrhosis and HCC, and removing stigmatization; meanwhile the overall goal is decreasing the global burden of HCV. IL-28B polymorphisms have been also associated with spontaneous clearance of vertically acquired HCV infection. The worldwide economic burden of HCV for children, families and countries is estimated to be hundreds of millions of US dollars per year. The United States, alone, is estimated to spend 199-336 million dollars in screening, monitoring and treatment during one decade. The emotional burden of having an HCV infected child in a family is more difficult to estimate.
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Beinhardt S, Payer BA, Datz C, Strasser M, Maieron A, Dorn L, Grilnberger-Franz E, Dulic-Lakovic E, Stauber R, Laferl H, Aberle JH, Holzmann H, Krall C, Vogel W, Ferenci P, Hofer H. A diagnostic score for the prediction of spontaneous resolution of acute hepatitis C virus infection. J Hepatol 2013; 59:972-7. [PMID: 23850880 DOI: 10.1016/j.jhep.2013.06.028] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2013] [Revised: 05/30/2013] [Accepted: 06/26/2013] [Indexed: 01/16/2023]
Abstract
BACKGROUND & AIMS IL28B polymorphisms, jaundice, decline in HCV-RNA, IP-10, and gender have been proposed to be indicative of spontaneous clearance of acute hepatitis C virus infection. The aim of this study was to define a score enabling the discrimination of patients with spontaneous clearance of HCV from those with development of viral persistence and need for early antiviral treatment. METHODS 136 patients (74 male; 35 ± 15 years) were analyzed. From variables predictive of spontaneous clearance, calculated by univariate analysis, three scores were built. Analogous cut-offs were evaluated by computing area under the receiver operating characteristic curves. Candidate variables and cut-offs were: (I) presence of IL28B C/C (p=0.027), (II) age (p=0.031; cut-off: 35 years), (III) peak-bilirubin (p=0.018; cut-off: 6 mg/dl), (IV) HCV-RNA decline within 4 weeks (p<0.001;cut-off: >2.5 log), (V) serum IP-10 (p=0.003; cut-off: 546 pg/ml), (VI) presence of CD4(+) Th1 cells (p=0.024). Each variable was allocated to 0 or 1 point, an HCV-RNA decline of ≥ 1 log 10 but <2.5 log 10 to 1 point, a decline of ≥ 2.5 log 10 to 2 points. Three scores were evaluated (Score 1: I-IV; Score 2: I-V; Score 3: I-VI). RESULTS A cut-off of ≥ 3 points out of 5 in Score 1 (AUROC: 0.82; DeLong 95% CI: 0.76-0.93) predicted spontaneous clearance with a sensitivity of 71% (95% CI: 0.53-0.86) and specificity of 87% (95% CI: 0.73-0.95). PPV and NPV were 79% and 82%. Corresponding findings for Score 2 including IP-10 (AUROC: 0.93; DeLong 95% CI: 0.86-0.93) at a cut-off of ≥ 4 were: sensitivity 81%, specificity 95% (PPV: 100%; NPV: 77%). A cut-off of ≥ 5 in Score 3 (AUROC: 0.98; DeLong 95% CI: 0.95-1.0) predicted spontaneous resolution with a sensitivity of 75% and specificity of 100% (PPV: 100%; NPV: 88%). CONCLUSIONS The scores enable a reliable discrimination between AHC-patients with high potential for spontaneous clearance from candidates for early therapeutic intervention due to marginal chance of spontaneous resolution.
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Affiliation(s)
- Sandra Beinhardt
- Internal Medicine III, Department of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
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Ciotti M, D'Agostini C, Marrone A. Advances in the Diagnosis and Monitoring of Hepatitis C Virus Infection. Gastroenterology Res 2013; 6:161-170. [PMID: 27785248 PMCID: PMC5051090 DOI: 10.4021/gr576e] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/03/2013] [Indexed: 12/18/2022] Open
Abstract
Hepatitis C virus (HCV) infection represents a major health problem worldwide. Approximately 350,000 people die every year from hepatitis C related diseases. Antiviral therapy is given to prevent such complications. Advances in serological and molecular assays greatly improved the diagnosis of hepatitis C virus infection and the management of chronically infected patients. Sensitive real-time PCR methods are currently used to monitor the response to antiviral therapy, to guide treatment decisions, and to assess the sustained virological response 24 weeks after the end of therapy. HCV genotyping is part of the pretreatment evaluation. Determination of HCV genotype is important both for tailoring antiviral treatment and for determining treatment duration. It predicts also response to therapy. With the recent introduction of the serine protease inhibitors telaprevir and boceprevir, approved for the treatment of genotype 1 chronic hepatitis C in combination with INF-a and ribavirin, subtyping has become clinically relevant. Indeed, subtypes 1a and 1b may respond differently to current telaprevir-based or boceprevir-based triple therapy. This review summarizes the most recent advances in the diagnosis and monitoring of HCV chronic infection.
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Affiliation(s)
- Marco Ciotti
- Laboratory of Molecular Virology, Polyclinic Tor Vergata Foundation, Viale Oxford 81-00133, Rome, Italy
| | - Cartesio D'Agostini
- Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Via Montpellier 1, 00133, Rome, Italy; Laboratory of Clinical Microbiology and Virology, Polyclinic "Tor Vergata" Foundation, Viale Oxford 81, 00133, Rome, Italy
| | - Aldo Marrone
- Internal Medicine and Hepatology, School of Medicine of Naples, Second University of Naples, Via Pansini 5, Edificio 10, 80131, Napoli, Italy
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