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Tham EKJ, Tan DJH, Danpanichkul P, Ng CH, Syn N, Koh B, Lim RYZ, Wijarnpreecha K, Teng MLP, Nah BKY, Sim BKL, Cheng X, Zhang Z, Mitra K, Nakamura T, Takahashi H, Loomba R, Zheng M, Muthiah M, Huang DQ. The Global Burden of Cirrhosis and Other Chronic Liver Diseases in 2021. Liver Int 2025; 45:e70001. [PMID: 39927433 PMCID: PMC11808647 DOI: 10.1111/liv.70001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 12/11/2024] [Accepted: 01/03/2025] [Indexed: 02/11/2025]
Abstract
BACKGROUND AND AIM The burden of cirrhosis and other chronic liver diseases has changed in recent years due to shifts in the contributing aetiologies. We estimated the burden of cirrhosis and other chronic liver diseases, including etiological and regional differences, across 204 countries and territories from 2010 to 2021. APPROACH AND RESULTS We analysed temporal trends in the burden of cirrhosis and other chronic liver diseases utilising data from the Global Burden of Disease Study 2021. We estimated annual frequencies and age-standardised rates (ASRs) of incident cases, deaths and disability-adjusted life-years (DALYs) by sex, country, World Health Organisation region and its contributing aetiologies. In 2021, there were an estimated 58 417 006 incident cases, 1 425 142 deaths and 46 417 777 DALYs related to cirrhosis and other chronic liver diseases. From 2010 to 2021, there was a rise in age-standardised incidence rates (ASIRs) (APC: +0.35%) but age-standardised death rates (ASDRs) (APC: -1.74%) and age-standardised disability-adjusted life-years (ASDALYs) (APC: -1.85%) declined. Cirrhosis related to metabolic dysfunction-associated steatohepatitis (MASH) contributed to 48 310 981 incident cases in 2021 and was largely responsible for the overall increase in ASIRs from 2010 to 2021. Cirrhosis and other chronic liver diseases related to MASH were the only aetiology with a rise in ASIR (APC: +0.86%). Age-standardised deaths related to all aetiologies of cirrhosis and other chronic liver diseases declined during the study period. Age-standardised deaths and DALYs related to MASH increased in the Americas, unlike all other world regions where they declined or remained stable. CONCLUSIONS Age-adjusted deaths related to cirrhosis and other chronic liver diseases are declining. However, the age-adjusted incidence of cirrhosis and other chronic liver diseases is increasing, driven by increases in the incidence of MASH.
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Affiliation(s)
- Ethan Kai Jun Tham
- Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
| | - Pojsakorn Danpanichkul
- Department of Internal MedicineTexas Tech University Health Sciences CenterLubbockTexasUSA
| | - Cheng Han Ng
- Division of Gastroenterology and Hepatology, Department of MedicineNational University HospitalSingaporeSingapore
- Division of Gastroenterology, Department of MedicineKurume University School of MedicineKurumeJapan
| | - Nicholas Syn
- Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
| | - Benjamin Koh
- Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
| | - Ryan Yan Zhe Lim
- Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
| | - Karn Wijarnpreecha
- Department of Internal MedicineBassett Medical CenterCooperstownNew YorkUSA
| | - Magaret Li Peng Teng
- Division of Gastroenterology, Department of MedicineAlexandra HospitalSingaporeSingapore
| | - Benjamin Kai Yi Nah
- Division of Gastroenterology and Hepatology, Department of MedicineNational University HospitalSingaporeSingapore
| | - Benedix Kuan Loo Sim
- Division of Gastroenterology and Hepatology, Department of MedicineNational University HospitalSingaporeSingapore
| | - Xianda Cheng
- Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
| | - Zixuan Zhang
- Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
| | - Kartik Mitra
- Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
| | - Toru Nakamura
- Division of Gastroenterology, Department of MedicineKurume University School of MedicineKurumeJapan
- Liver Cancer Research DivisionKurume University Research Center for Innovative, Cancer TherapyKurumeJapan
| | - Hirokazu Takahashi
- Division of Metabolism and Endocrinology, Faculty of MedicineSaga UniversitySagaJapan
| | - Rohit Loomba
- Division of Gastroenterology, Department of Medicine and Division of Epidemiology, Department of Family and Preventive MedicineUniversity of CaliforniaSan DiegoCaliforniaUSA
- Division of Gastroenterology and Hepatology, Department of Medicine, MASLD Research CenterUniversity of California at San DiegoLa JollaCaliforniaUSA
| | - Ming‐Hua Zheng
- Department of Hepatology, MAFLD Research CenterThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
- Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang ProvinceZhejiangWenzhouChina
| | - Mark Muthiah
- Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
- Division of Gastroenterology and Hepatology, Department of MedicineNational University HospitalSingaporeSingapore
- National University Centre for Organ TransplantationNational University Health SystemSingaporeSingapore
| | - Daniel Q. Huang
- Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
- Division of Gastroenterology and Hepatology, Department of MedicineNational University HospitalSingaporeSingapore
- National University Centre for Organ TransplantationNational University Health SystemSingaporeSingapore
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Fleurence RL, Alter HJ, Collins FS, Ward JW. Global Elimination of Hepatitis C Virus. Annu Rev Med 2025; 76:29-41. [PMID: 39485830 DOI: 10.1146/annurev-med-050223-111239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2024]
Abstract
Hepatitis C virus (HCV) is predominantly transmitted through parenteral exposures to infectious blood or body fluids. In 2019, approximately 58 million people worldwide were infected with HCV, and 290,000 deaths occurred due to hepatitis C-related conditions, despite hepatitis C being curable. There are substantial barriers to elimination, including the lack of widespread point-of-care diagnostics, cost of treatment, stigma associated with hepatitis C, and challenges in reaching marginalized populations, such as people who inject drugs. The World Health Organization (WHO) has set goals to eliminate hepatitis C by 2030. Several countries, including Australia, Egypt, Georgia, and Rwanda, have made remarkable progress toward hepatitis C elimination. In the United States, the Biden-Harris administration recently issued a plan for the national elimination of hepatitis C. Global progress has been uneven, however, and will need to accelerate considerably to reach the WHO's 2030 goals. Nevertheless, the global elimination of hepatitis C is within reach and should remain a high public health priority.
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Affiliation(s)
- Rachael L Fleurence
- Office of the Director, National Institutes of Health, Bethesda, Maryland, USA;
| | - Harvey J Alter
- Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
| | - Francis S Collins
- National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - John W Ward
- Task Force for Global Health, Decatur, Georgia, USA
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Ly KN, Barker LK, Kilmer G, Shing JZ, Jiles RB, Teshale E. Disparities in hepatitis C among people aged 12-59 with no history of injection drug use, United States, January 2013-March 2020. Liver Int 2024; 44:3250-3259. [PMID: 39324414 PMCID: PMC11927374 DOI: 10.1111/liv.16108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 08/21/2024] [Accepted: 09/11/2024] [Indexed: 09/27/2024]
Abstract
BACKGROUND AND AIMS In the United States, hepatitis C virus (HCV) infection occurs primarily through injection drug use (IDU), but transmission also occurs through other ways. This study examined HCV prevalence and disparities among US residents aged 12-59 years with no IDU history. METHODS We analysed 2013-March 2020 National Health and Nutrition Examination Survey data to calculate the HCV prevalence among people with no drug use history and only a non-IDU history, collectively referred to as no IDU history. These estimates were compared to those with an IDU history and stratified by sociodemographic and hepatitis A and hepatitis B serologic characteristics. RESULTS The current HCV infection prevalence among people aged 12-59 was .7% overall, and specifically 17.2% among people with an IDU history, .9% among people with a non-IDU history and .2% among people with no drug use history. These rates represented 1.4 million people with current HCV infection, of whom, 730 000 had an IDU history, 262 000 had a non-IDU history and 309 000 had no drug use history. Among people with no drug use history, current HCV infection prevalence was higher for people born during 1954-1965 versus after 1965, had completed high school or less versus at least some college and had past/present hepatitis B versus vaccinated for hepatitis B. CONCLUSION While the HCV infection burden was highest among people with an IDU history, we found a sizeable burden among people without such a history. These findings support policies and practices aimed at addressing disparities among people needing treatment.
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Affiliation(s)
- Kathleen N Ly
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, US Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Laurie K Barker
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, US Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Greta Kilmer
- Division of Population Health, National Center for Chronic Disease Prevention and Health Promotion, US Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Jaimie Z Shing
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Ruth B Jiles
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, US Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Eyasu Teshale
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, US Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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4
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Masterman C, Mendlowitz AB, Capraru C, Campbell K, Eastabrook G, Yudin MH, Kushner T, Flemming JA, Feld JJ, Babenko-Mould Y, Tryphonopoulos P, Biondi M. An evolutionary concept analysis: stigma among women living with hepatitis C. BMC Public Health 2024; 24:2660. [PMID: 39342214 PMCID: PMC11439273 DOI: 10.1186/s12889-024-20131-6] [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: 01/06/2024] [Accepted: 09/19/2024] [Indexed: 10/01/2024] Open
Abstract
BACKGROUND Stigma is a complex social phenomenon that leads to marginalization and influences the course of illness. In the context of hepatitis C virus (HCV), stigma is a well-documented barrier to accessing care, treatment, and cure. In recent years, HCV rates among women have increased, resulting in an urgent need to address stigma and its harmful effects. The purpose of this concept analysis was to investigate stigma in the context of women living with HCV using Rodgers' evolutionary method. METHODS PubMed, CINAHL, Scopus, Medline, PsycINFO, and Nursing and Allied Health were used to identify articles describing HCV stigma among women. Articles from peer-reviewed journals and geographic locations, published between 2002-2023, were included in the analysis. As specified in Rodgers' evolutionary method, articles were analyzed with a focus on the concept's context, surrogate and related terms, antecedents, attributes, examples, and consequences. RESULTS Following screening, 33 articles were selected for inclusion in the analysis. Discrimination and marginalization were identified as surrogate and related terms to stigma; and antecedents of stigma were identified as limited knowledge, fear of diagnosis, and disclosure. Prevalent attributes of stigma in the literature were described as feelings of decreased self-worth, negative stereotyping, and fear of transmission. Importantly, HCV stigma among women is unique in comparison to other forms of infectious disease-related stigma, primarily due its impact on women's identity as mothers and caregivers. Stigmatization of women living with HCV resulted in negative consequences to personal relationships and healthcare access due to decreased health-seeking behaviours. Although access to HCV treatment has changed considerably over time, a temporal analysis could not be completed due to the limited number of articles. CONCLUSIONS Stigma in the context of women living with HCV has its own unique antecedents, attributes, and consequences. This enhanced understanding of stigma among women living with HCV has the potential to inform improved and more effective approaches to care, which will be required to reach HCV elimination. Furthermore, this analysis identifies stigma layering and stigma in the direct-acting antiviral treatment era as areas for more in-depth future inquiry.
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Affiliation(s)
- Chelsea Masterman
- Arthur Labatt Family School of Nursing, Western University, London, ON, Canada
| | - Andrew B Mendlowitz
- Viral Hepatitis Care Network (VIRCAN) Study Group, Toronto Centre for Liver Disease, Toronto, ON, Canada
| | - Camelia Capraru
- Viral Hepatitis Care Network (VIRCAN) Study Group, Toronto Centre for Liver Disease, Toronto, ON, Canada
| | | | | | - Mark H Yudin
- Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON, Canada
| | - Tatyana Kushner
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jennifer A Flemming
- Department of Medicine and Public Health Sciences, Queen's University, Kingston, ON, Canada
| | - Jordan J Feld
- Viral Hepatitis Care Network (VIRCAN) Study Group, Toronto Centre for Liver Disease, Toronto, ON, Canada
| | | | | | - Mia Biondi
- Arthur Labatt Family School of Nursing, Western University, London, ON, Canada.
- Viral Hepatitis Care Network (VIRCAN) Study Group, Toronto Centre for Liver Disease, Toronto, ON, Canada.
- School of Nursing, York University, Toronto, ON, Canada.
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Rollin F, McNamara M, Aleuy L, Lom J, Chirumamilla S, Molinari A, Miller L, Fluker SA. Real world experience in treatment of chronic hepatitis C in patients with compensated and decompensated cirrhosis. Future Virol 2024; 19:393-399. [DOI: 10.1080/17460794.2024.2415213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 10/08/2024] [Indexed: 01/03/2025]
Affiliation(s)
- Francois Rollin
- Department of Medicine, Emory University School of Medicine
- Grady Liver Clinic, Grady Health Systems, Atlanta, GA 30303, USA
| | - Maeve McNamara
- Emory University School of Medicine, Atlanta, GA 30303, USA
| | - Lana Aleuy
- Department of Medicine, Emory University School of Medicine
| | - Jennifer Lom
- Department of Medicine, Emory University School of Medicine
- Grady Liver Clinic, Grady Health Systems, Atlanta, GA 30303, USA
| | - Siri Chirumamilla
- Family and Preventive Medicine, Emory University School of Medicine, Atlanta, GA 30303, USA
| | - Alexander Molinari
- Family and Preventive Medicine, Emory University School of Medicine, Atlanta, GA 30303, USA
| | - Lesley Miller
- Department of Medicine, Emory University School of Medicine
- Grady Liver Clinic, Grady Health Systems, Atlanta, GA 30303, USA
| | - Shelly-Ann Fluker
- Department of Medicine, Emory University School of Medicine
- Grady Liver Clinic, Grady Health Systems, Atlanta, GA 30303, USA
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Hleyhel M, Geller J, Sadou A, Naaber P, Kuznetsova T, Vorobjov S, Lõhmus M, Furegato M, Reed S, Bluemel B, Duffell E, Rüütel K. Prevalence of chronic hepatitis C infection in the general population: results from a national survey, Estonia, July to December 2022. Euro Surveill 2024; 29:2300651. [PMID: 39056201 PMCID: PMC11274846 DOI: 10.2807/1560-7917.es.2024.29.30.2300651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Accepted: 06/10/2024] [Indexed: 07/28/2024] Open
Abstract
IntroductionObtaining epidemiological data on chronic hepatitis C virus (HCV) infection is essential to monitor progress towards the hepatitis C elimination targets.AimWe aimed to estimate the prevalence of chronic HCV and the seroprevalence of HCV in the adult general population in Estonia.MethodsThis cross-sectional study, conducted between 12 July and 6 December 2022, included anonymised residual sera collected prospectively from patients 18 years and older visiting a general practitioner in all counties of Estonia. Specimens were considered HCV-seropositive if they tested positive for HCV antibodies by enzyme-linked immunoassay, confirmed by line-immunoblot assay. Chronic HCV infection was determined by positive RT-qPCR.ResultsWe tested a total of 4,217 specimens. The estimated HCV seroprevalence and prevalence of chronic HCV infection were 1.8% (95% CI: 1.4-2.2) and 0.8% (95% CI: 0.5-1.1), respectively, with ca 8,100 persons estimated to have chronic HCV infection in the general adult population of Estonia. No statistically significant differences in the prevalence of chronic HCV infection were observed between sexes, counties or age groups, with the highest prevalence rates observed in men (sex ratio: 1.7), Ida-Virumaa County (1.8%; 95% CI: 0.8-3.6) and the age group 40-49 years (1.7%; 95% CI: 0.9-2.9).ConclusionThis study found an overall low prevalence of chronic HCV infection in Estonia. Continued efforts should be made for the targeted screening, diagnosis and treatment of individuals with chronic HCV infection to achieve hepatitis elimination targets.
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Affiliation(s)
- Mira Hleyhel
- Cerner Enviza/Oracle Life Sciences, Paris, France
| | - Julia Geller
- National Institute for Health Development, Tallinn, Estonia
| | - Amal Sadou
- Cerner Enviza/Oracle Life Sciences, Paris, France
| | - Paul Naaber
- Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia
- SYNLAB Estonia, Tallinn, Estonia
| | | | | | | | | | - Suzanne Reed
- Cerner Enviza/Oracle Life Sciences, Paris, France
| | - Benjamin Bluemel
- European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden
| | - Erika Duffell
- European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden
| | - Kristi Rüütel
- National Institute for Health Development, Tallinn, Estonia
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McNamara M, Furukawa N, Cartwright EJ. Advancing Hepatitis C Elimination through Opt-Out Universal Screening and Treatment in Carceral Settings, United States. Emerg Infect Dis 2024; 30:S80-S87. [PMID: 38561831 PMCID: PMC10986823 DOI: 10.3201/eid3013.230859] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/04/2024] Open
Abstract
Incarcerated persons are infected with hepatitis C virus (HCV) at rates ≈10 times higher than that of the general population in the United States. To achieve national hepatitis C elimination goals, the diagnosis and treatment of hepatitis C in incarcerated persons must be prioritized. In 2022, the Centers for Disease Control and Prevention recommended that all persons receive opt-out HCV screening upon entry into a carceral setting. We review recommendations, treatments, and policy strategies used to promote HCV opt-out universal HCV screening and treatment in incarcerated populations in the United States. Treatment of hepatitis C in carceral settings has increased but varies by jurisdiction and is not sufficient to achieve HCV elimination. Strengthening universal HCV screening and treatment of HCV-infected incarcerated persons is necessary for HCV elimination nationwide.
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Tanaka T, Lentine KL, Shi Q, Vander Weg M, Axelrod DA. Differential Impact of the UNOS Simultaneous Liver-kidney Transplant Policy Change Among Patients With Sustained Acute Kidney Injury. Transplantation 2024; 108:724-731. [PMID: 37677960 DOI: 10.1097/tp.0000000000004774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/09/2023]
Abstract
BACKGROUND Simultaneous liver-kidney transplant (SLK) allocation policy in the United States was revised in August 2017, reducing access for liver transplant candidates with sustained acute kidney injury (sAKI) and potentially adversely impacting vulnerable populations whose true renal function is overestimated by commonly used estimation equations. METHODS We examined national transplant registry data containing information for all liver transplant recipients from June 2013 to December 2021 to assess the impact of this policy change using instrumental variable estimation based on date of listing. RESULTS Posttransplant survival was compared for propensity-matched patients with sAKI who were only eligible for liver transplant alone (LTA_post; n = 638) after the policy change but would have been SLK-eligible before August 2017, with similar patients who were previously able to receive an SLK (SLK; n = 319). Overall posttransplant patient survival was similar at 3 y (81% versus 80%; P = 0.9). However, receiving an SLK versus LTA increased survival among African Americans (87% versus 61% at 3 y; P = 0.029). A trend toward survival benefit from SLK versus LTA, especially later in the follow-up period, was observed in recipients ≥ age 60 (3-y survival: 84% versus 76%; P = 0.2) and women (86% versus 80%; P = 0.2). CONCLUSIONS The 2017 United Network for Organ Sharing SLK Allocation Policy was associated with reduced survival of African Americans with end-stage liver disease and sAKI and, potentially, older patients and women. Our study suggested the use of race-neutral estimation of renal function would ameliorate racial disparities in the SLK arena; however, further studies are needed to reduce disparity in posttransplant outcomes among patients with liver and kidney failure.
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Affiliation(s)
- Tomohiro Tanaka
- Division of Gastroenterology and Hepatology, University of Iowa Carver College of Medicine, Iowa City, IA
- Center for Access & Delivery Research and Evaluation (CADRE), Iowa City VA Health Care System, Iowa City, IA
- University of Iowa Carver College of Medicine, Iowa City, IA
| | - Krista L Lentine
- Saint Louis University Transplant Center, SSM-Saint Louis University Hospital, St. Louis, MO
| | - Qianyi Shi
- Center for Access & Delivery Research and Evaluation (CADRE), Iowa City VA Health Care System, Iowa City, IA
- University of Iowa Carver College of Medicine, Iowa City, IA
| | - Mark Vander Weg
- Center for Access & Delivery Research and Evaluation (CADRE), Iowa City VA Health Care System, Iowa City, IA
- Department of Community and Behavioral Health, College of Public Health, University of Iowa, Iowa City, IA
| | - David A Axelrod
- Division of Transplantation and Hepatobiliary Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
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Wong XK, Ng CS, Yeong KY. Shaping the future of antiviral Treatment: Spotlight on Nucleobase-Containing drugs and their revolutionary impact. Bioorg Chem 2024; 144:107150. [PMID: 38309002 DOI: 10.1016/j.bioorg.2024.107150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 12/28/2023] [Accepted: 01/22/2024] [Indexed: 02/05/2024]
Abstract
Nucleobases serve as essential molecular frameworks present in both natural and synthetic compounds that exhibit notable antiviral activity. Through molecular modifications, novel nucleobase-containing drugs (NCDs) have been developed, exhibiting enhanced antiviral activity against a wide range of viruses, including the recently emerged SARS‑CoV‑2. This article provides a detailed examination of the significant advancements in NCDs from 2015 till current, encompassing various aspects concerning their mechanisms of action, pharmacology and antiviral properties. Additionally, the article discusses antiviral prodrugs relevant to the scope of this review. It fills in the knowledge gap by examining the structure-activity relationship and trend of NCDs as therapeutics against a diverse range of viral diseases, either as approved drugs, clinical candidates or as early-stage development prospects. Moreover, the article highlights on the status of this field of study and addresses the prevailing limitations encountered.
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Affiliation(s)
- Xi Khai Wong
- School of Science, Monash University (Malaysia Campus), Jalan Lagoon Selatan, Bandar Sunway, 47500 Subang Jaya, Selangor, Malaysia
| | - Chen Seng Ng
- School of Science, Monash University (Malaysia Campus), Jalan Lagoon Selatan, Bandar Sunway, 47500 Subang Jaya, Selangor, Malaysia
| | - Keng Yoon Yeong
- School of Science, Monash University (Malaysia Campus), Jalan Lagoon Selatan, Bandar Sunway, 47500 Subang Jaya, Selangor, Malaysia.
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Ly KN, Niles JK, Jiles RB, Kaufman HW, Weng MK, Patel P, Meyer WA, Thompson WW, Thompson ND. Hepatitis C Virus Testing, Infection, and Cases Reported Through Public Health Surveillance During Expanded Screening Recommendations, United States, 2013-2021. Public Health Rep 2024:333549231224199. [PMID: 38344828 PMCID: PMC11363629 DOI: 10.1177/00333549231224199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/01/2024] Open
Abstract
OBJECTIVES Hepatitis C virus (HCV) infection is the most common bloodborne infection in the United States. We assessed trends in HCV testing, infection, and surveillance cases among US adults. METHODS We used Quest Diagnostics data from 2013-2021 to assess trends in the numbers tested for HCV antibody and proportion of positivity for HCV antibody and HCV RNA. We also assessed National Notifiable Diseases Surveillance System 2013-2020 data for trends in the number and proportion of hepatitis C cases. We applied joinpoint regression for trends testing. RESULTS Annual HCV antibody testing increased from 1.7 million to 4.8 million from 2013 to 2021, and the positivity proportion declined (average, 0.2% per year) from 5.5% to 3.7%. The greatest percentage-point increase in HCV antibody testing occurred in hospitals and substance use disorder treatment facilities and among addiction medicine providers. HCV RNA positivity was stable at about 60% in 2013-2015 and declined to 41.0% in 2021 (2015-2021 average, -3.2% per year). Age-specific HCV RNA positivity was highest among people aged 40-59 years during 2013-2015 and among people aged 18-39 years during 2016-2021. The number of reported hepatitis C cases (acute and chronic) declined from 179 341 in 2015 to 105 504 in 2020 (average decline, -13 177 per year). The proportion of hepatitis C cases among those aged 18-39 years increased by an average of 1.4% per year during 2013-2020; among individuals aged 40-59 years, it decreased by an average of 2.3% per year during 2013-2018. CONCLUSIONS HCV testing increased, suggesting improved universal screening. Various data sources are valuable for monitoring elimination progress.
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Affiliation(s)
- Kathleen N. Ly
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | | | - Ruth B. Jiles
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | | | - Mark K. Weng
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Priti Patel
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | | | - William W. Thompson
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Nicola D. Thompson
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
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Diani E, Lagni A, Lotti V, Tonon E, Cecchetto R, Gibellini D. Vector-Transmitted Flaviviruses: An Antiviral Molecules Overview. Microorganisms 2023; 11:2427. [PMID: 37894085 PMCID: PMC10608811 DOI: 10.3390/microorganisms11102427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 09/18/2023] [Accepted: 09/25/2023] [Indexed: 10/29/2023] Open
Abstract
Flaviviruses cause numerous pathologies in humans across a broad clinical spectrum with potentially severe clinical manifestations, including hemorrhagic and neurological disorders. Among human flaviviruses, some viral proteins show high conservation and are good candidates as targets for drug design. From an epidemiological point of view, flaviviruses cause more than 400 million cases of infection worldwide each year. In particular, the Yellow Fever, dengue, West Nile, and Zika viruses have high morbidity and mortality-about an estimated 20,000 deaths per year. As they depend on human vectors, they have expanded their geographical range in recent years due to altered climatic and social conditions. Despite these epidemiological and clinical premises, there are limited antiviral treatments for these infections. In this review, we describe the major compounds that are currently under evaluation for the treatment of flavivirus infections and the challenges faced during clinical trials, outlining their mechanisms of action in order to present an overview of ongoing studies. According to our review, the absence of approved antivirals for flaviviruses led to in vitro and in vivo experiments aimed at identifying compounds that can interfere with one or more viral cycle steps. Still, the currently unavailability of approved antivirals poses a significant public health issue.
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Affiliation(s)
- Erica Diani
- Department of Diagnostic and Public Health, Microbiology Section, University of Verona, 37134 Verona, Italy; (A.L.); (V.L.); (R.C.)
| | - Anna Lagni
- Department of Diagnostic and Public Health, Microbiology Section, University of Verona, 37134 Verona, Italy; (A.L.); (V.L.); (R.C.)
| | - Virginia Lotti
- Department of Diagnostic and Public Health, Microbiology Section, University of Verona, 37134 Verona, Italy; (A.L.); (V.L.); (R.C.)
| | - Emil Tonon
- Unit of Microbiology, Azienda Ospedaliera Universitaria Integrata Verona, 37134 Verona, Italy;
| | - Riccardo Cecchetto
- Department of Diagnostic and Public Health, Microbiology Section, University of Verona, 37134 Verona, Italy; (A.L.); (V.L.); (R.C.)
- Unit of Microbiology, Azienda Ospedaliera Universitaria Integrata Verona, 37134 Verona, Italy;
| | - Davide Gibellini
- Department of Diagnostic and Public Health, Microbiology Section, University of Verona, 37134 Verona, Italy; (A.L.); (V.L.); (R.C.)
- Unit of Microbiology, Azienda Ospedaliera Universitaria Integrata Verona, 37134 Verona, Italy;
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12
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Shaikh A, Goli K, Lee TH, Rich NE, Benhammou JN, Keeling S, Kim D, Ahmed A, Goss J, Rana A, Singal AG, Kanwal F, Cholankeril G. Reduction in Racial and Ethnic Disparity in Survival Following Liver Transplant for Hepatocellular Carcinoma in the Direct-acting Antiviral Era. Clin Gastroenterol Hepatol 2023; 21:2288-2297.e4. [PMID: 36521738 PMCID: PMC10686256 DOI: 10.1016/j.cgh.2022.11.038] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 11/24/2022] [Accepted: 11/30/2022] [Indexed: 01/07/2023]
Abstract
BACKGROUND & AIMS Black patients with hepatocellular cancer (HCC), often attributed to hepatitis C virus (HCV) infection, have suboptimal survival following liver transplant (LT). We evaluated the impact of direct-acting antiviral (DAA) availability on racial and ethnic disparities in wait list burden post-LT survival for candidates with HCC. METHODS Using the United Network for Organ Sharing registry, we identified patients with HCC who were listed and/or underwent LT from 2009 to 2020. Based on date of LT, patients were categorized into 2 era-based cohorts: the pre-DAA era (LT between 2009 and 2011) and DAA era (LT between 2015 and 2017, with follow-up through 2020). Kaplan-Meier and Cox proportional hazards analyses were used to compare post-LT survival, stratified by era and race and ethnicity. RESULTS Annual wait list additions for HCV-related HCC decreased significantly in White and Hispanic patients during the DAA era, with no change (P = .14) in Black patients. Black patients had lower 3-year survival than White patients in the pre-DAA era (70.6% vs 80.1%, respectively; P < .001) but comparable survival in the DAA era (82.1% vs 85.5%, respectively; P = .16). 0n multivariable analysis, Black patients in the pre-DAA era had a 53% higher risk (adjusted hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.28-1.84), for mortality than White patients, but mortality was comparable in the DAA era (adjusted HR, 1.23; 95% CI, 0.99-1.52). In a stratified analysis in Black patients, HCV-related HCC carried more than a 2-fold higher risk of mortality in the pre-DAA era (adjusted HR, 2.86; 95% CI, 1.50-5.43), which was reduced in the DAA era (adjusted HR, 1.34; 95% CI, 0.78-2.30). CONCLUSIONS With the availability of DAA therapy, racial disparities in post-LT survival have improved.
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Affiliation(s)
- Anjiya Shaikh
- Department of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut
| | - Karthik Goli
- Department of Student Affairs, Baylor College of Medicine, Houston, Texas
| | - Tzu-Hao Lee
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas; Hepatology Program, Division of Abdominal Transplantation, Michael E DeBakey Department of General Surgery, Baylor College of Medicine, Houston, Texas
| | - Nicole E Rich
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas
| | - Jihane N Benhammou
- The Vatche and Tamar Manoukian Division of Digestive Diseases, University of California at Los Angeles, Los Angeles, California
| | - Stephanie Keeling
- Department of Student Affairs, Baylor College of Medicine, Houston, Texas
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford, California
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford, California
| | - John Goss
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Abbas Rana
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Amit G Singal
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas
| | - Fasiha Kanwal
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas; Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - George Cholankeril
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas; Hepatology Program, Division of Abdominal Transplantation, Michael E DeBakey Department of General Surgery, Baylor College of Medicine, Houston, Texas.
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13
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Rodprasert N, Hongboontry T, Cherdchoochart C, Chaiteerakij R. Association between Liver Stiffness and Liver-Related Events in HCV-Infected Patients after Successful Treatment with Direct-Acting Antivirals. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59030602. [PMID: 36984603 PMCID: PMC10053469 DOI: 10.3390/medicina59030602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 03/11/2023] [Accepted: 03/15/2023] [Indexed: 03/30/2023]
Abstract
Background and Objectives: Direct-acting antivirals (DAAs) are highly effective for the treatment of chronic hepatitis C virus (HCV) infection, but the risk of liver-related events and hepatocellular carcinoma (HCC) remains after successful therapy. We aimed to evaluate post-treatment changes in liver stiffness (LS) and identify a cut-off LS value for predicting such events in chronic HCV-infected patients receiving DAA. Materials and Methods: A total of 185 patients who had achieved sustained virologic response (SVR) after DAA therapy were included. Baseline characteristics and laboratory results were retrospectively abstracted. LS was measured by transient elastography at baseline, 12, 24, 48, and 96 weeks after SVR. FIB-4 index was assessed at baseline and 48 weeks after SVR. Development of liver-related events (hepatocellular carcinoma (HCC), portal-hypertension-related decompensation, listing for transplantation, and mortality) after SVR were identified. The association between liver fibrosis and the occurrence of liver-related events was analyzed using Cox regression analysis. Results: Significant differences in LS values were observed between baseline and 24, 48, 72, and 96 weeks after SVR. FIB-4 index at 48 weeks after SVR was significantly lower than the FIB-4 index at baseline. During the 41.6-month follow-up time, the incidence rates of all liver-related events and HCC were 2.36 and 1.17 per 100 person-years, respectively. Age, LS ≥8 kPa, and FIB-4 ≥1.35 at 48 weeks post-SVR were significantly associated with the occurrence of any liver-related events. By multivariate analysis, LS ≥8 kPa at 48 weeks post-SVR remained significantly associated with any liver-related events, with an adjusted hazard ratio (95%CI) of 5.04 (1.01-25.26), p = 0.049. Conclusions: Despite a significant reduction in LS after SVR, patients with LS ≥8 kPa at 48 weeks after SVR should be regularly monitored for liver-related complications, particularly HCC development.
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Affiliation(s)
- Napas Rodprasert
- Division of Gastroenterology, Department of Medicine, King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand
| | - Tinn Hongboontry
- Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | | | - Roongruedee Chaiteerakij
- Division of Gastroenterology, Department of Medicine, King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
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14
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Swe TM, Johnson DC, Mar HT, Thit P, Homan T, Chu CM, Mon PE, Thwe TT, Soe KP, Ei WLSS, Tun NL, Lwin KZ, Karakozian H, Aung KS, Nguyen A, Ciglenecki I, Tamayo N, Loarec A. Epidemiological characteristics and real-world treatment outcomes of hepatitis C among HIV/HCV co-infected patients in Myanmar: A prospective cohort study. Health Sci Rep 2023; 6:e1119. [PMID: 36819986 PMCID: PMC9938359 DOI: 10.1002/hsr2.1119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 02/04/2023] [Accepted: 02/07/2023] [Indexed: 02/20/2023] Open
Abstract
Background and Aims In Myanmar, public sector treatment programs for hepatitis C virus (HCV) infection were nonexistent until June 2017. WHO highlights the importance of simplification of HCV service delivery through task-shifting among health workers and decentralization to the primary health care level. Between November 2016 and November 2017, a study was conducted to describe the epidemiological data and real-world outcomes of treating HIV/HCV coinfected patients with generic direct acting antiviral (DAA) based regimens in the three HIV clinics run by nonspecialist medical doctors in Myanmar. Methods HCV co-infection among people living with HIV (PLHIV) from two clinics in Yangon city and one clinic in Dawei city was screened by rapid diagnostic tests and confirmed by testing for viral RNA. Nonspecialist medical doctors prescribed sofosbuvir and daclatasvir based regimens (with or without ribavirin) for 12 or 24 weeks based on the HCV genotype and liver fibrosis status. Sustained virologic response at 12 weeks after treatment (SVR12) was assessed to determine cure. Results About 6.5% (1417/21,777) of PLHIV were co-infected with HCV. Of 864 patients enrolled in the study, 50.8% reported history of substance use, 27% history of invasive medical procedures and 25.6% history of incarceration. Data on treatment outcomes were collected from 267 patients of which 257 (96.3%) achieved SVR12, 7 (2.6%) failed treatment, 2 (0.7%) died and 1 (0.4%) became loss to follow-up. Conclusion The study results support the integration of hepatitis C diagnosis and treatment with DAA-based regimens into existing HIV clinics run by nonspecialist medical doctors in a resource-limited setting. Epidemiological data on HIV/HCV co-infection call for comprehensive HCV care services among key populations like drug users and prisoners in Yangon and Dawei.
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Affiliation(s)
- Thein Min Swe
- Medecins Sans FrontieresDaweiMyanmar
- Medecins Sans FrontieresYangonMyanmar
| | | | | | | | | | | | | | | | | | | | | | | | | | - Khin Sanda Aung
- National Hepatitis Control Program, Ministry of Health and SportsNaypyitawMyanmar
| | - Aude Nguyen
- Medecins Sans FrontieresGenevaSwitzerland
- Infectious Diseases Unit, Geneva University HospitalsGenevaSwitzerland
| | | | | | - Anne Loarec
- Epicentre, Medecins Sans FrontieresParisFrance
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15
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Transplantation of Organs from Hepatitis C Virus-Positive Donors under Direct-Acting Antiviral Regimens. J Clin Med 2022; 11:jcm11030770. [PMID: 35160222 PMCID: PMC8836390 DOI: 10.3390/jcm11030770] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 12/28/2021] [Accepted: 01/27/2022] [Indexed: 01/27/2023] Open
Abstract
There is a discrepancy between the patients requiring organ transplants and the donors available to meet that demand. Many patients die every year while on the waiting list, and there is a need to bridge this gap. For many years, medical practitioners have been apprehensive of using donor organs from donors who have tested positive for the Hepatitis C virus (HCV), and with good reason. HCV has been proven to be among the leading causes of liver diseases requiring liver transplants. Over the years, studies have been carried out to find a treatment for Hepatitis C. The advent of direct-acting antivirals revolutionized the medical world. These medication regimens have been proven to treat Hepatitis C in transplant patients effectively. This systematic review will examine how DAA treatments affect transplants of different organs from HCV-positive donors to HCV-negative recipients.
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Virseda-Berdices A, Brochado-Kith O, Díez C, Hontañon V, Berenguer J, González-García J, Rojo D, Fernández-Rodríguez A, Ibañez-Samaniego L, Llop-Herrera E, Olveira A, Perez-Latorre L, Barbas C, Rava M, Resino S, Jiménez-Sousa MA. Blood microbiome is associated with changes in portal hypertension after successful direct-acting antiviral therapy in patients with HCV-related cirrhosis. J Antimicrob Chemother 2021; 77:719-726. [PMID: 34888660 DOI: 10.1093/jac/dkab444] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 11/08/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Patients with a significant decrease in hepatic venous pressure gradient (HVPG) have a considerable reduction of liver complications and higher survival after HCV eradication. OBJECTIVES To evaluate the association between the baseline blood microbiome and the changes in HVPG after successful direct-acting antiviral (DAA) therapy in patients with HCV-related cirrhosis. METHODS We performed a prospective study in 32 cirrhotic patients (21 HIV positive) with clinically significant portal hypertension (HVPG ≥10 mmHg). Patients were assessed at baseline and 48 weeks after HCV treatment completion. The clinical endpoint was a decrease in HVPG of ≥20% or HVPG <12 mmHg at the end of follow-up. Bacterial 16S ribosomal DNA was sequenced using MiSeq Illumina technology, inflammatory plasma biomarkers were investigated using ProcartaPlex immunoassays and the metabolome was investigated using GC-MS. RESULTS During the follow-up, 47% of patients reached the clinical endpoint. At baseline, those patients had a higher relative abundance of Corynebacteriales and Diplorickettsiales order, Diplorickettsiaceae family, Corynebacterium and Aquicella genus and Undibacterium parvum species organisms and a lower relative abundance of Oceanospirillales and Rhodospirillales order, Halomonadaceae family and Massilia genus organisms compared with those who did not achieve the clinical endpoint according to the LEfSe algorithm. Corynebacteriales and Massilia were consistently found within the 10 bacterial taxa with the highest differential abundance between groups. Additionally, the relative abundance of the Corynebacteriales order was inversely correlated with IFN-γ, IL-17A and TNF-α levels and the Massilia genus with glycerol and lauric acid. CONCLUSIONS Baseline-specific bacterial taxa are related to an HVPG decrease in patients with HCV-related cirrhosis after successful DAA therapy.
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Affiliation(s)
- Ana Virseda-Berdices
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain
| | - Oscar Brochado-Kith
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain.,Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Cristina Díez
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.,Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario 'Gregorio Marañón', Madrid, Spain.,Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Victor Hontañon
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.,Servicio de Medicina Interna-Unidad de VIH, Hospital Universitario La Paz, Madrid, Spain.,Instituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, Spain
| | - Juan Berenguer
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.,Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario 'Gregorio Marañón', Madrid, Spain.,Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Juan González-García
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.,Servicio de Medicina Interna-Unidad de VIH, Hospital Universitario La Paz, Madrid, Spain.,Instituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, Spain
| | - David Rojo
- Centre for Metabolomics and Bioanalysis (CEMBIO), Department of Chemistry and Biochemistry, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28660 Boadilla del Monte, Madrid, Spain
| | - Amanda Fernández-Rodríguez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain.,Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Luis Ibañez-Samaniego
- Servicio de Aparato Digestivo, Hospital General Universitario 'Gregorio Marañón', Madrid, Spain
| | - Elba Llop-Herrera
- Departamento de Gastroenterología, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Madrid, Spain
| | - Antonio Olveira
- Servicio de Aparato Digestivo, Hospital Universitario La Paz, Madrid, Spain
| | - Leire Perez-Latorre
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.,Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario 'Gregorio Marañón', Madrid, Spain.,Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Coral Barbas
- Centre for Metabolomics and Bioanalysis (CEMBIO), Department of Chemistry and Biochemistry, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28660 Boadilla del Monte, Madrid, Spain
| | - Marta Rava
- Unidad de la Cohorte de la Red de Investigación en Sida (CoRIS), Centro Nacional de Epidemiologia (CNE), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Salvador Resino
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain.,Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - María Angeles Jiménez-Sousa
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain.,Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
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17
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Ly KN, Miniño AM, Liu SJ, Roberts H, Hughes EM, Ward JW, Jiles RB. Deaths Associated With Hepatitis C Virus Infection Among Residents in 50 States and the District of Columbia, 2016-2017. Clin Infect Dis 2020; 71:1149-1160. [PMID: 31586173 PMCID: PMC11089524 DOI: 10.1093/cid/ciz976] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Accepted: 10/02/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Mortality associated with hepatitis C virus (HCV) has been well-documented nationally, but an examination across regions and jurisdictions may inform health-care planning. METHODS To document HCV-associated deaths sub-nationally, we calculated age-adjusted, HCV-associated death rates and compared death rate ratios (DRRs) for 10 US regions, 50 states, and Washington, D.C., using the national rate and described rate changes between 2016 and 2017 to determine variability. We examined the mean age at HCV-associated death, and rates and proportions by sex, race/ethnicity, and birth year. RESULTS In 2017, there were 17 253 HCV-associated deaths, representing 4.13 (95% confidence interval [CI], 4.07-4.20) deaths/100 000 standard population, in a significant, 6.56% rate decline from 4.42 in 2016. Age-adjusted death rates significantly surpassed the US rate for the following jurisdictions: Oklahoma; Washington, D.C.; Oregon; New Mexico; Louisiana; Texas; Colorado; California; Kentucky; Tennessee; Arizona; and Washington (DRRs, 2.87, 2.77, 2.24, 1.62, 1.57, 1.46, 1.36, 1.35, 1.35, 1.35, 1.32, and 1.32, respectively; P < .05). Death rates ranged from a low of 1.60 (95% CI, 1.07-2.29) in Maine to a high of 11.84 (95% CI, 10.82-12.85) in Oklahoma. Death rates were highest among non-Hispanic (non-H) American Indians/Alaska Natives and non-H Blacks, both nationally and regionally. The mean age at death was 61.4 years (range, 56.6 years in West Virginia to 64.1 years in Washington, D.C.), and 78.6% of those who died were born during 1945-1965. CONCLUSIONS In 2016-2017, the national HCV-associated mortality declined but rates remained high in the Western and Southern regions and Washington, D.C., and among non-H American Indians/Alaska Natives, non-H Blacks, and Baby Boomers. These data can inform local prevention and control programs to reduce the HCV mortality burden.
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Affiliation(s)
- Kathleen N Ly
- Division of Viral Hepatitis, National Center for Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome, Viral Hepatitis, Sexually Transmitted Disease, and Tuberculosis Prevention, US Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Arialdi M Miniño
- Division of Vital Statistics, National Center for Health Statistics, US Centers for Disease Control and Prevention, Hyattsville, Maryland, USA, Pittsburg, Pennsylvania, USA
| | - Stephen J Liu
- Graduate School of Public Health, University of Pittsburg, Pittsburg, Pennsylvania, USA
| | - Henry Roberts
- Division of Viral Hepatitis, National Center for Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome, Viral Hepatitis, Sexually Transmitted Disease, and Tuberculosis Prevention, US Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Elizabeth M Hughes
- Division of Viral Hepatitis, National Center for Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome, Viral Hepatitis, Sexually Transmitted Disease, and Tuberculosis Prevention, US Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - John W Ward
- Coalition for Global Hepatitis Elimination, The Task Force for Global Health, Decatur, Georgia, USA
| | - Ruth B Jiles
- Division of Viral Hepatitis, National Center for Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome, Viral Hepatitis, Sexually Transmitted Disease, and Tuberculosis Prevention, US Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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18
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McGinnis KA, Suffoletto MS. The U. S. Department of Veterans Affairs (VA) as a model for stronger public health infrastructure to combat HCV and other infectious diseases and reduce disparities. EClinicalMedicine 2020; 22:100391. [PMID: 32478316 PMCID: PMC7251646 DOI: 10.1016/j.eclinm.2020.100391] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 05/05/2020] [Indexed: 01/08/2023] Open
Affiliation(s)
| | - Matthew S. Suffoletto
- Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
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19
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Inoue T, Ohike T, Ohne K, Sato S, Goto T, Tanaka Y. Clinical Evaluation of a Newly Developed Chemiluminescent Enzyme Immunoassay for Hepatitis C Virus Core Antigen in Japan. Jpn J Infect Dis 2019; 72:285-291. [PMID: 30918148 DOI: 10.7883/yoken.jjid.2018.472] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
An advanced and fully automated chemiluminescent enzyme immunoassay for the hepatitis C virus core antigen (HCVcAg) was recently developed in Japan. We aimed to evaluate its clinical utility. The new Fujirebio assay (Lumipulse Presto HCVcAg [LP-Presto]) was compared with 2 conventional assays (Lumipulse Ortho HCVcAg [LP-Ortho] and Abbott's Architect HCVcAg). Basic assessments of LP-Presto (reproducibility, stability, range of quantitation, and specificity) were performed on 220 frozen sera (83 positive and 137 negative by LP-Ortho) and 206 fresh sera (all negative by LP-Ortho). Correlation analysis was performed and the rates of concordance for each assay were determined. Additionally, the frozen sera of 42 hyperimmunoglobulinemia patients, including 3 unmeasurable by LP-Ortho, were tested by LP-Presto. All the basic assessments of LP-Presto were consistent with the results of LP-Ortho and Architect. The concordance rate between LP-Presto and LP-Ortho for the 220 frozen sera was 99.5% (219/220), and that between LP-Presto and Architect was 99.1% (218/220). LP-Presto (HCVcAg cut-off value; 20 fmol/L) was fully consistent with LP-Ortho (100%), which found 343 sera negative for HCVcAg. All 42 hyperimmunoglobulinemic sera were measurable using LP-Presto. In conclusion, the performance of LP-Presto was rapid and reliable, and nonspecific test results due to hyperimmunoglobulinemia were reduced when LP-Presto was used. Therefore, LP-Presto is a high-quality HCVcAg assay that shows promising applications.
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Affiliation(s)
- Takako Inoue
- Department of Clinical Laboratory Medicine, Nagoya City University Hospital
| | | | - Kumiko Ohne
- Clinical Laboratory, Nagoya City University Hospital
| | - Shigeru Sato
- Clinical Laboratory, Nagoya City University Hospital
| | - Takaaki Goto
- Clinical Laboratory, Nagoya City University Hospital
| | - Yasuhito Tanaka
- Department of Clinical Laboratory Medicine, Nagoya City University Hospital.,Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences
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Girardin F, Hearmon N, Negro F, Eddowes L, Bruggmann P, Castro E. Increasing hepatitis C virus screening in people who inject drugs in Switzerland using rapid antibody saliva and dried blood spot testing: A cost-effectiveness analysis. J Viral Hepat 2019; 26:236-245. [PMID: 30338887 DOI: 10.1111/jvh.13023] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Accepted: 09/18/2018] [Indexed: 01/20/2023]
Abstract
People who inject drugs (PWID) are a key high-risk group for Hepatitis C Virus (HCV) infection due to the sharing of needles and drug-preparation equipment. However, only approximately 50% of PWID are currently screened for HCV in Switzerland. At present, screening of PWID occurs in general practice via venepuncture. Compared to venepuncture, screening via rapid antibody saliva and dried blood spot (DBS) tests is well adapted to PWID, who typically have difficult venous access. The cost-effectiveness of an increased access screening programme of PWID (increased screening using rapid antibody saliva tests and DBS tests [semi-quantitative viraemia and viral genotype]) was analysed through a decision tree screening model combined with the outputs of a Markov treatment model. Sensitivity and scenario analyses examined the uncertainty of results. At a willingness to pay (WTP) threshold of CHF 100 000 (USD 105 000) per quality-adjusted life year (QALY), the increased access screening programme was cost-effective compared to current screening, with a base case incremental cost-effectiveness ratio of CHF 7 940 (USD 8337) per QALY. The net monetary benefit was CHF 959 802 668 (USD 1 007 792 801) for the PWID population and CHF 94 469 (USD 99 192) per person. The increased access screening programme had a 97.0% probability of being cost-effective compared to the current screening method at the WTP threshold of CHF 100 000 (USD 105 000). The results showed an increased access screening programme that uses tests which are better suited to the PWID population to be more cost-effective, due to the increased uptake that rapid antibody saliva and DBS tests generate.
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Affiliation(s)
- François Girardin
- Medical Direction and Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, University of Geneva, Geneva, Switzerland.,Faculty of Business and Economics, University of Lausanne, Lausanne, Switzerland
| | | | - Francesco Negro
- Divisions of Gastroenterology and Hepatology and of Clinical Pathology, HUG, Geneva, Switzerland
| | | | | | - Erika Castro
- Center for Addiction Medicine, Service of Community Psychiatry, Department of Psychiatry, University of Lausanne (CHUV), Lausanne, Switzerland
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21
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Pecoraro V, Banzi R, Cariani E, Chester J, Villa E, D'Amico R, Bertele' V, Trenti T. New Direct-Acting Antivirals for the Treatment of Patients With Hepatitis C Virus Infection: A Systematic Review of Randomized Controlled Trials. J Clin Exp Hepatol 2019; 9:522-538. [PMID: 31516269 PMCID: PMC6728536 DOI: 10.1016/j.jceh.2018.07.004] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Accepted: 07/07/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND New direct-acting antiviral agents (DAAs) approved for the treatment of patients infected by Hepatitis C virus (HCV) are well tolerated and increase sustained virological response (SVR) rate. We summarize current evidence on the efficacy and safety from comparative randomized controlled trials (RCTs) of DAAs. METHODS We systematically searched MEDLINE, Embase, Scopus, CENTRAL, and Lilacs as well as a list of reference literature. We included RCTs comparing DAAs with placebo or active control and reporting response rates and adverse events according to antiviral regimens. Risk ratios (RRs) were pooled as appropriate. We assessed the risk of bias of included studies and graded the quality of evidence according to the GRADE method. RESULTS We included 28 RCTs, enrolling more than 7000 patients. The quality of evidence was generally low. Twelve-week treatment with DAAs in naïve patients significantly increased SVR12 and SVR24 compared with placebo (RR 1.4, 95% CI 1.3-1.6; RR 1.5, 95% CI 1.4-1.6, respectively). This means that for every 1000 patients, 240 or 260 more patients experienced SVR12 or SVR24 if treated with any DAAs. We could not find RCTs assessing progression of liver disease or development of hepatocellular carcinoma. DAAs were not associated with higher incidence of serious adverse events or discontinuation due to adverse events. CONCLUSIONS This systematic review confirms that new DAAs are more effective in inducing SVR than placebo. Outside clinical trials, in real word, HCV cure with DAA regimens occurs in less than 90% of patients, so further comparative evaluations are needed to establish their long-term effects.
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Key Words
- AE, adverse event
- CI, confidence interval
- DAA, direct-acting antiviral agent
- HCC, hepatocellular carcinoma
- HCV, Hepatitis C virus
- NNPIs, nonnucleoside polymerase inhibitors
- NPIs, nucleoside polymerase inhibitors
- PEG-IFN, pegylated interferon
- PrIs, protease inhibitors
- RAVs, resistance-associated variants
- RBV, Ribavirin
- RCT, randomized controlled trial
- RR, risk ratio
- SAEs, serious adverse events
- SE, standard error
- SVR, sustained virological response
- hepatitis C
- liver
- meta-analysis
- outcome research
- systematic review
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Affiliation(s)
- Valentina Pecoraro
- Unit of Laboratory Medicine, Ospedale Civile Sant'Agostino Estense, Modena, Italy,Center for Drug Regulatory Policies, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy,Address for correspondence. Pecoraro Valentina, Unit of Laboratory Medicine, Ospedale Civile Sant'Agostino Estense, Modena, Italy.
| | - Rita Banzi
- Center for Drug Regulatory Policies, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - Elisabetta Cariani
- Unit of Laboratory Medicine, Ospedale Civile Sant'Agostino Estense, Modena, Italy
| | - Johanna Chester
- Department of Surgery, Medical, Dentistry and Morphological Sciences, University of Modena e Reggio Emilia, Italy
| | - Erica Villa
- Department of Gastroenterology – AOU Modena, Modena, Italy
| | - Roberto D'Amico
- Cochrane Italy – University of Modena and Reggio Emilia, Italy
| | - Vittorio Bertele'
- Center for Drug Regulatory Policies, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - Tommaso Trenti
- Unit of Laboratory Medicine, Ospedale Civile Sant'Agostino Estense, Modena, Italy
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22
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Buchanan-Hughes AM, Buti M, Hanman K, Langford B, Wright M, Eddowes LA. Health state utility values measured using the EuroQol 5-dimensions questionnaire in adults with chronic hepatitis C: a systematic literature review and meta-analysis. Qual Life Res 2018; 28:297-319. [PMID: 30225787 DOI: 10.1007/s11136-018-1992-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/31/2018] [Indexed: 01/27/2023]
Abstract
PURPOSE Chronic hepatitis C infection and its treatment can considerably affect patients' health-related quality-of-life (HRQoL). This study aimed to identify and summarise the current evidence base for health state utility values (HSUVs) in patients with chronic hepatitis C infection, generated using the EuroQol 5-dimensions (EQ-5D) questionnaire. METHODS MEDLINE, Embase, the Cochrane Library and EconLit were searched from database inception through 31 August 2017. Eligible studies reported HSUVs elicited using the EQ-5D questionnaire in adults with chronic hepatitis C infection. Study quality and risk of bias were assessed. RESULTS Of 1480 records identified, 26 studies were included. The most commonly defined health states described different stages of chronic hepatitis C infection and specific liver-related disease states, including METAVIR score, compensated and decompensated cirrhosis, hepatocellular carcinoma and liver transplantation. Patients with higher METAVIR scores tended to have lower EQ-5D scores compared to patients with lower METAVIR scores. Patients that achieved sustained virologic responses tended to have higher EQ-5D scores compared to those that did not. A meta-analysis conducted on three studies confirmed that patients with decompensated cirrhosis have significantly lower HSUVs than patients with compensated cirrhosis [mean difference - 0.11 (95% CI - 0.19 to - 0.04)], implying worse HRQoL. However, there was not sufficient evidence to compare how different treatments for chronic hepatitis C infection affect EQ-5D scores. CONCLUSIONS This study provides a summary of EQ-5D HSUVs for patients with chronic hepatitis C infection, and demonstrates that clinically important disease stages associated with treatment decisions are associated with differences in HRQoL.
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Affiliation(s)
| | - M Buti
- Hospital Universitario Valle Hebron, Barcelona, Spain.,Ciberehd del Instituto Carlos III, Madrid, Spain
| | - K Hanman
- Costello Medical Consulting Ltd, Cambridge, UK
| | - B Langford
- Costello Medical Consulting Ltd, Cambridge, UK
| | - M Wright
- University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - L A Eddowes
- Costello Medical Consulting Ltd, Cambridge, UK
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23
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Inoue T, Goto T, Iio E, Matsunami K, Fujiwara K, Shinkai N, Matsuura K, Matsui T, Nojiri S, Tanaka Y. Changes in serum lipid profiles caused by three regimens of interferon-free direct-acting antivirals for patients infected with hepatitis C virus. Hepatol Res 2018; 48:E203-E212. [PMID: 28834042 DOI: 10.1111/hepr.12970] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2017] [Revised: 06/30/2017] [Accepted: 08/15/2017] [Indexed: 02/06/2023]
Abstract
AIM Serum low-density lipoprotein cholesterol (LDL-C) increases during treatment of chronic hepatitis C (CHC) with interferon-free direct-acting antivirals (DAAs). We sought to compare the changes of serum lipid profiles caused by three regimens. METHODS A total of 216 CHC patients were enrolled. Among 170 patients infected with hepatitis C virus (HCV) genotype 1b, 85 received daclatasvir plus asunaprevir (DCV/ASV) and 85 received sofosbuvir plus ledipasvir (SOF/LDV). Forty-six infected with HCV genotype 2 received sofosbuvir plus ribavirin (SOF/RBV). Serum total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol, and triglyceride were measured at baseline and 4, 8, 12 (for all regimens), and 24 weeks (for DCV/ASV) during treatment (4w, 8w, 12w, and 24w, respectively) and 12 and 24 weeks after treatment (p12w and p24w, respectively). RESULTS In 69 (81.2%) patients who received DCV/ASV and achieved a sustained virologic response at 24 weeks after the end of treatment (SVR24), TC and LDL-C increased significantly from baseline to p24w. In 84 (98.8%) treated with SOF/LDV who achieved SVR24, TC and LDL-C increased significantly from baseline to 8w, and TC decreased significantly from 8w to p12w. The 45 (97.8%) who received SOF/RBV and achieved SVR24 showed no significant changes. At 12w, TC and LDL-C increased to a greater degree in patients receiving SOF/LDV than in those receiving DCV/ASV or SOF/RBV. CONCLUSION During treatment with DAAs, the serum lipid profile may reflect not only recovery from the disruption of lipid metabolism induced by HCV, but also the pharmacological effects of DAAs. Further investigations are needed to elucidate the effect of DAAs on serum lipid profiles.
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Affiliation(s)
- Takako Inoue
- Department of Clinical Laboratory, Nagoya City University Hospital, Nagoya, Japan
| | - Takaaki Goto
- Department of Clinical Laboratory, Nagoya City University Hospital, Nagoya, Japan
| | - Etsuko Iio
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kayoko Matsunami
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kei Fujiwara
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Noboru Shinkai
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kentaro Matsuura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Takeshi Matsui
- Teine Keijinkai Hospital, Sapporo, Japan.,Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shunsuke Nojiri
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yasuhito Tanaka
- Department of Clinical Laboratory, Nagoya City University Hospital, Nagoya, Japan.,Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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24
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Taherkhani R, Farshadpour F. Lurking epidemic of hepatitis C virus infection in Iran: A call to action. World J Hepatol 2017; 9:1040-1042. [PMID: 28932350 PMCID: PMC5583536 DOI: 10.4254/wjh.v9.i24.1040] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Revised: 06/19/2017] [Accepted: 07/17/2017] [Indexed: 02/06/2023] Open
Abstract
Despite having a relatively low prevalence in the Iranian general population, the burden of hepatitis C virus (HCV) infection is on the rise, and hepatitis C is predicted to be the most important leading cause of viral hepatitis-related mortality in the near future in Iran. The recent population-based epidemiological studies have revealed the predominant role of injecting drug use in increasing prevalence of HCV infection. Undoubtedly, new management paradigm is required to drive down the rising wave of hepatitis C in Iran. Priority should be given to young injecting drug users as the cornerstone of the lurking epidemic of HCV infection in Iran.
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Affiliation(s)
- Reza Taherkhani
- the Persian Gulf Biomedical Research Center, Bushehr University of Medical Sciences, Bushehr 7514633341, Iran
| | - Fatemeh Farshadpour
- the Persian Gulf Tropical Medicine Research Center, Bushehr University of Medical Sciences, Bushehr 7514633341, Iran
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25
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Shawky SM, Awad AM, Allam W, Alkordi MH, El-Khamisy SF. Gold aggregating gold: A novel nanoparticle biosensor approach for the direct quantification of hepatitis C virus RNA in clinical samples. Biosens Bioelectron 2017; 92:349-356. [PMID: 27836599 PMCID: PMC5345390 DOI: 10.1016/j.bios.2016.11.001] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Revised: 10/30/2016] [Accepted: 11/01/2016] [Indexed: 12/14/2022]
Abstract
The affordable and reliable detection of Hepatitis C Virus (HCV) RNA is a cornerstone in the management and control of infection, affecting approximately 3% of the global population. However, the existing technologies are expensive, labor intensive and time consuming, posing significant limitations to their wide-scale exploitation, particularly in economically deprived populations. Here, we utilized the unique optical and physicochemical properties of gold nanoparticles (AuNPs) to develop a novel assay platform shown to be rapid and robust in sensing and quantifying unamplified HCV RNA in clinical samples. The assay is based on inducing aggregation of citrate AuNPs decorated with a specific nucleic acid probe. Two types of cationic AuNPs, cysteamine and CTAB capped, were compared to achieve maximum assay performance. The technology is simple, rapid, cost effective and quantitative with 93.3% sensitivity, high specificity and detection limit of 4.57IU/µl. Finally, our data suggest that RNA folding impact the aggregation behavior of the functionalized AuNPs, with broader applications in other nucleic acid detection technologies.
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Affiliation(s)
- Sherif M Shawky
- Center of Genomics, Helmy institute, Zewail City of Science and Technology, Sheikh Zayed Dist., 12588 Giza, Egypt; Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, UK; Misr University for Science and Technology, Faculty of Pharmacy, Biochemistry Department, Giza, Egypt
| | - Ahmed M Awad
- Center of Genomics, Helmy institute, Zewail City of Science and Technology, Sheikh Zayed Dist., 12588 Giza, Egypt
| | - Walaa Allam
- Center of Genomics, Helmy institute, Zewail City of Science and Technology, Sheikh Zayed Dist., 12588 Giza, Egypt
| | - Mohamed H Alkordi
- Center for Materials Science, Zewail City of Science and Technology, Sheikh Zayed Dist., 12588 Giza, Egypt
| | - Sherif F El-Khamisy
- Center of Genomics, Helmy institute, Zewail City of Science and Technology, Sheikh Zayed Dist., 12588 Giza, Egypt; Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, UK.
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26
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Inoue T, Hmwe SS, Shimada N, Kato K, Ide T, Torimura T, Kumada T, Toyoda H, Tsubota A, Takaguchi K, Wakita T, Tanaka Y. Clinical Significance of Two Real-Time PCR Assays for Chronic Hepatitis C Patients Receiving Protease Inhibitor-Based Therapy. PLoS One 2017; 12:e0170667. [PMID: 28118381 PMCID: PMC5261727 DOI: 10.1371/journal.pone.0170667] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2016] [Accepted: 01/09/2017] [Indexed: 12/20/2022] Open
Abstract
The aim of this study was to determine the efficacy of two hepatitis C virus (HCV) real-time PCR assays, the COBAS AmpliPrep/COBAS TaqMan HCV test (CAP/CTM) and the Abbott RealTime HCV test (ART), for predicting the clinical outcomes of patients infected with HCV who received telaprevir (TVR)-based triple therapy or daclatasvir/asunaprevir (DCV/ASV) dual therapy. The rapid virological response rates in patients receiving TVR-based triple therapy were 92% (23/25) and 40% (10/25) for CAP/CTM and ART, respectively. The false omission rate (FOR) of ART was 93.3% (14/15), indicating that CAP/CTM could accurately predict clinical outcome in the early phase. In an independent examination of 20 patients receiving TVR-based triple therapy who developed viral breakthrough or relapse, the times to HCV disappearance by ART were longer than by CAP/CTM, whereas the times to HCV reappearance were similar. In an independent experiment of WHO standard HCV RNA serially diluted in serum containing TVR, the analytical sensitivities of CAP/CTM and ART were similar. However, cell cultures transfected with HCV and grown in medium containing TVR demonstrated that ART detected HCV RNA for a longer time than CAP/CTM. Similar results were found for 42 patients receiving DCV/ASV dual therapy. The FOR of ART was 73.3% (11/15) at week 8 after initiation of therapy, indicating that ART at week 8 could not accurately predict the clinical outcome. In conclusion, although CAP/CTM and ART detected HCV RNA with comparable analytical sensitivity, CAP/CTM might be preferable for predicting the clinical outcomes of patients receiving protease inhibitor-based therapy.
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Affiliation(s)
- Takako Inoue
- Department of Clinical Laboratory, Nagoya City University Hospital, Nagoya, Japan
| | - Su Su Hmwe
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
| | - Noritomo Shimada
- Ootakanomori Hospital, Kashiwa, Japan
- Division of Gastroenterology and Hepatology, Shin-Matsudo Central General Hospital, Matsudo, Japan
| | - Keizo Kato
- Division of Gastroenterology and Hepatology, Shin-Matsudo Central General Hospital, Matsudo, Japan
| | - Tatsuya Ide
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Takuji Torimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Takashi Kumada
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Akihito Tsubota
- Institute of Clinical Medicine and Research, The Jikei University School of Medicine, Kashiwa, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Takaji Wakita
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
| | - Yasuhito Tanaka
- Department of Clinical Laboratory, Nagoya City University Hospital, Nagoya, Japan
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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27
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State of the Art, Unresolved Issues, and Future Research Directions in the Fight against Hepatitis C Virus: Perspectives for Screening, Diagnostics of Resistances, and Immunization. J Immunol Res 2016; 2016:1412840. [PMID: 27843956 PMCID: PMC5098088 DOI: 10.1155/2016/1412840] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Revised: 09/09/2016] [Accepted: 09/20/2016] [Indexed: 12/13/2022] Open
Abstract
Hepatitis C virus (HCV) still represents a major public health threat, with a dramatic burden from both epidemiological and clinical points of view. New generation of direct-acting antiviral agents (DAAs) has been recently introduced in clinical practice promising to cure HCV and to overcome the issues related to the interferon-based therapies. However, the emergence of drug resistance and the suboptimal activity of DAAs therapies against diverse HCV genotypes have been observed, determining treatment failure and hampering an effective control of HCV spread worldwide. Moreover, these treatments remain poorly accessible, particularly in low-income countries. Finally, effective screening strategy is crucial to early identifying and treating all HCV chronically infected patients. For all these reasons, even though new drugs may contribute to impacting HCV spread worldwide a preventive HCV vaccine remains a cornerstone in the road to significantly reduce the HCV spread globally, with the ultimate goal of its eradication. Advances in molecular vaccinology, together with a strong financial, political, and societal support, will enable reaching this fundamental success in the coming years. In this comprehensive review, the state of the art about these major topics in the fight against HCV and the future of research in these fields are discussed.
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28
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Sarpel D, Dieterich DT. C-WORTHY: the beginning of the rise of elbasvir and grazoprevir for the treatment of hepatitis C genotype 1 mono and HIV co-infected patients. ANNALS OF TRANSLATIONAL MEDICINE 2016; 4:S12. [PMID: 27867980 DOI: 10.21037/atm.2016.09.22] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Affiliation(s)
- Dost Sarpel
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
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29
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Gane EJ, Schwabe C, Hyland RH, Yang Y, Svarovskaia E, Stamm LM, Brainard DM, McHutchison JG, Stedman CA. Efficacy of the Combination of Sofosbuvir, Velpatasvir, and the NS3/4A Protease Inhibitor GS-9857 in Treatment-Naïve or Previously Treated Patients With Hepatitis C Virus Genotype 1 or 3 Infections. Gastroenterology 2016; 151:448-456.e1. [PMID: 27240903 DOI: 10.1053/j.gastro.2016.05.021] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2016] [Revised: 05/12/2016] [Accepted: 05/19/2016] [Indexed: 12/21/2022]
Abstract
BACKGROUND & AIMS We performed a phase 2 trial of the efficacy and safety of 4, 6, and 8 weeks of sofosbuvir, given in combination with the NS5A inhibitor velpatasvir and the NS3/4A protease inhibitor GS-9857, in patients with hepatitis C virus (HCV) infection. METHODS We enrolled 161 treatment-naïve or previously treated patients infected with HCV genotypes 1 or 3 with or without compensated cirrhosis at 2 centers in New Zealand, from September 2014 through March 2015. All patients received sofosbuvir (400 mg) and velpatasvir (100 mg) plus GS-9857 (100 mg) once daily. The primary efficacy end point was sustained virologic response at 12 weeks after therapy (SVR12). The duration of therapy was determined by baseline patient characteristics: 4 or 6 weeks for treatment-naïve patients without cirrhosis, 6 weeks for treatment-naïve patients with cirrhosis, and 6 or 8 weeks for treatment-experienced patients with or without cirrhosis. RESULTS Four weeks of sofosbuvir, velpatasvir, and GS-9857 produced an SVR12 in 4 of 15 (27%) treatment-naïve patients with HCV genotype 1 without cirrhosis. Six weeks of this combination produced a SVR12 in 14 of 15 (93%) treatment-naïve patients with HCV genotype 1 without cirrhosis, in 13 of 15 (87%) treatment-naïve genotype 1 patients with cirrhosis, in 15 of 18 (83%) treatment-naïve patients with HCV genotype 3 with cirrhosis, and in 20 of 30 (67%) patients with HCV genotype 1 who had failed an all-oral regimen of 2 or more direct-acting antiviral agents. Eight weeks of the drug combination produced an SVR12 in 17 of 17 (100%) patients with HCV genotype 1, in 19 of 19 (100%) patients with HCV genotype 3 and cirrhosis who had failed pegylated interferon plus ribavirin, in 25 of 28 (89%) patients with HCV genotype 1 who had failed protease inhibitor-based triple therapy, and in 4 of 4 (100%) patients with HCV genotype 3 who had failed an all-oral regimen of ≥2 direct-acting antiviral agents. The most common reported adverse events were headache, nausea, and fatigue. CONCLUSIONS Eight weeks of treatment with the combination of sofosbuvir, velpatasvir, and GS-9857 produced an SVR12 in most treatment-naïve or previously treated patients with HCV genotype 1 or 3 infections, including those with compensated cirrhosis. ClinicalTrials.gov, Number: NCT02202980.
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Affiliation(s)
- Edward J Gane
- New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand.
| | | | | | - Yin Yang
- Gilead Sciences, Inc, Foster City, California
| | | | | | | | | | - Catherine A Stedman
- Gastroenterology Department, Christchurch Hospital, and University of Otago, Christchurch, New Zealand
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30
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Mean platelet volume and red cell distribution width to platelet ratio for predicting the severity of hepatic fibrosis in patients with chronic hepatitis C. Eur J Gastroenterol Hepatol 2016; 28:744-8. [PMID: 27101403 DOI: 10.1097/meg.0000000000000647] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
OBJECTIVE We designed this study to investigate the relationship between the severity of fibrosis and mean platelet volume (MPV), red cell distribution width, and red cell distribution width to platelet ratio (RPR) in patients with chronic hepatitis C (CHC). DESIGN Overall, 98 biopsy-proven naïve CHC cases were enrolled in the study. Complete blood count variables, including white blood cell, hemoglobin, platelet count, MPV, red cell distribution width, platelet distribution width as well as aspartate transaminase, alanine transaminase, total bilirubin, albumin, and other routine biochemical parameters, were tested. Liver biopsy samples were assessed according to the Ishak scoring system. Data analyses were carried out using SPSS-15 software. Statistical significance was set at a P-value of less than 0.05. RESULTS Of the 98 cases, 80 (81.6%) were men and 18 (18.4%) were women. Fibrosis scores of 69 cases (70.4%) (group 1) were less than 3, whereas 29 cases had fibrosis scores at least 3 (29.6%) (group 2). Significant differences in MPV and RPR were observed between these two groups (MPV: 8.19±1.002 vs. 8.63±0.67 fl, P<0.05; RPR: 0.0526±0.02 vs. 0.0726±0.02, P=0.001). The areas under the curve of the RPR and MPV for predicting significant fibrosis were 0.705 and 0.670, which was superior to the aspartate transaminase-to-alanine transaminase ratio and aspartate transaminase-to-platelet ratio index scores of the study group. Cut-off values were calculated for diagnostic performance, and the cut-off values for MPV and RPR were 8.5 and 0.07 fl, respectively. CONCLUSION MPV and RPR values were significantly higher in patients with CHC, associated with severity, and can be used to predict advanced histological liver damage. The use of MPV and RPR may reduce the need for liver biopsy. Further studies are required to determine the relationship between these parameters and the severity of fibrosis in hepatitis C patients.
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31
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Yarbrough ML, Burnham CAD. The ABCs of STIs: An Update on Sexually Transmitted Infections. Clin Chem 2016; 62:811-23. [PMID: 27076632 DOI: 10.1373/clinchem.2015.240234] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Accepted: 03/11/2016] [Indexed: 12/17/2022]
Abstract
BACKGROUND Sexually transmitted infections (STIs) are spread primarily through sexual contact and are a major cause of morbidity and mortality worldwide. Once identified, some STIs can be cured following appropriate therapy; for others, suppressive regimens and approaches to prevent ongoing transmission are important. The incidence of many common STIs is increasing in the US as well as worldwide, and hundreds of millions of people are currently infected. Laboratory testing plays a major role in the diagnosis and treatment of STIs, and clinical laboratorians should be familiar with the current guidelines and methods for testing. CONTENT Accurate and sensitive methods to diagnose STIs are essential to direct appropriate antimicrobial therapy and interrupt the cycle of disease transmission. This review summarizes laboratory testing for common bacterial, viral, and parasitic causes of STIs. Disease manifestations reviewed include cervicitis and urethritis, genital ulcerative disease, human immunodeficiency virus, viral hepatitis, human papilloma virus, and vaginitis. Recent advancements in the recognition and management of STIs, including updates to diagnostic algorithms, advances in testing methods, and emerging challenges with antimicrobial resistance, are summarized. SUMMARY Diagnostic methods and therapeutic guidelines for STIs are rapidly evolving. In combination with changing epidemiology, the development of novel therapeutics, and advancements in diagnostic methods, this has resulted in changing practices in laboratory testing and, subsequently, management of disease. Molecular methods have facilitated personalized therapy and follow-up regimens targeted for individual types or strains of some STIs.
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Affiliation(s)
- Melanie L Yarbrough
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110
| | - Carey-Ann D Burnham
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
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Prolactin Regulatory Element Binding Protein Is Involved in Hepatitis C Virus Replication by Interaction with NS4B. J Virol 2016; 90:3093-111. [PMID: 26739056 DOI: 10.1128/jvi.01540-15] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2015] [Accepted: 12/30/2015] [Indexed: 12/12/2022] Open
Abstract
UNLABELLED It has been proposed that the hepatitis C virus (HCV) NS4B protein triggers the membranous HCV replication compartment, but the underlying molecular mechanism is not fully understood. Here, we screened for NS4B-associated membrane proteins by tandem affinity purification and proteome analysis and identified 202 host proteins. Subsequent screening of replicon cells with small interfering RNA identified prolactin regulatory element binding (PREB) to be a novel HCV host cofactor. The interaction between PREB and NS4B was confirmed by immunoprecipitation, immunofluorescence, and proximity ligation assays. PREB colocalized with double-stranded RNA and the newly synthesized HCV RNA labeled with bromouridine triphosphate in HCV replicon cells. Furthermore, PREB shifted to detergent-resistant membranes (DRMs), where HCV replication complexes reside, in the presence of NS4B expression in Huh7 cells. However, a PREB mutant lacking the NS4B-binding region (PREBd3) could not colocalize with double-stranded RNA and did not shift to the DRM in the presence of NS4B. These results indicate that PREB locates at the HCV replication complex by interacting with NS4B. PREB silencing inhibited the formation of the membranous HCV replication compartment and increased the protease and nuclease sensitivity of HCV replicase proteins and RNA in DRMs, respectively. Collectively, these data indicate that PREB promotes HCV RNA replication by participating in the formation of the membranous replication compartment and by maintaining its proper structure by interacting with NS4B. Furthermore, PREB was induced by HCV infection in vitro and in vivo. Our findings provide new insights into HCV host cofactors. IMPORTANCE The hepatitis C virus (HCV) protein NS4B can induce alteration of the endoplasmic reticulum and the formation of a membranous web structure, which provides a platform for the HCV replication complex. The molecular mechanism by which NS4B induces the membranous HCV replication compartment is not understood. We screened for NS4B-associated membrane proteins by tandem affinity purification and proteome analysis, followed by screening with small interfering RNA. We identified prolactin regulatory element binding (PREB) to be a novel HCV host cofactor. PREB is induced by HCV infection and recruited into the replication complex by interaction with NS4B. Recruited PREB promotes HCV RNA replication by participating in the formation of the membranous HCV replication compartment. To our knowledge, the effect of NS4B-binding protein on the formation of the membranous HCV replication compartment is newly described in this report. Our findings are expected to provide new insights into HCV host cofactors.
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