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Infectious Disease Clinics of North... Jun 2018The world has embraced the call for global elimination of hepatitis C virus by 2030. The unprecedented speed of therapeutic development and increased access to... (Review)
Review
The world has embraced the call for global elimination of hepatitis C virus by 2030. The unprecedented speed of therapeutic development and increased access to direct-acting antivirals has made elimination a possibility. We must screen hundreds of millions of people to diagnose and treat those currently infected. Global access to hepatitis C virus diagnostics will be a keystone to success. Key challenges must be overcome and systems optimized to ensure widespread access to existing diagnostics. Although promising technologies may soon transform the landscape, innovative strategies are needed to stimulate investment and accelerate the development of point-of-care hepatitis C virus diagnostics.
Topics: Antiviral Agents; Disease Eradication; Global Health; Hepacivirus; Hepatitis C; Humans; Molecular Diagnostic Techniques; Point-of-Care Systems; Substance Abuse, Intravenous
PubMed: 29778264
DOI: 10.1016/j.idc.2018.02.010 -
Current Topics in Microbiology and... 2013Hepatitis C virus (HCV) is a hepatotropic virus and a major cause of chronic hepatitis and liver disease worldwide. Initial interactions between HCV virions and... (Review)
Review
Hepatitis C virus (HCV) is a hepatotropic virus and a major cause of chronic hepatitis and liver disease worldwide. Initial interactions between HCV virions and hepatocytes are required for productive viral infection and initiation of the viral life cycle. Furthermore, HCV entry contributes to the tissue tropism and species specificity of this virus. The elucidation of these interactions is critical, not only to understand the pathogenesis of HCV infection, but also to design efficient antiviral strategies and vaccines. This review summarizes our current knowledge of the host factors required for the HCV-host interactions during HCV binding and entry, our understanding of the molecular mechanisms underlying HCV entry into target cells, and the relevance of HCV entry for the pathogenesis of liver disease, antiviral therapy, and vaccine development.
Topics: Animals; Antiviral Agents; Hepacivirus; Hepatitis C; Host-Pathogen Interactions; Humans; Virus Attachment; Virus Internalization
PubMed: 23463198
DOI: 10.1007/978-3-642-27340-7_4 -
Liver International : Official Journal... Mar 2019Hepatitis C has a relevant global impact in terms of morbidity, mortality and economic costs, with more than 70 million people infected worldwide. In the resolution,... (Review)
Review
Hepatitis C has a relevant global impact in terms of morbidity, mortality and economic costs, with more than 70 million people infected worldwide. In the resolution, "Transforming our world: the 2030 Agenda for Sustainable Development" was included as a focus area in the health-related goal with world leaders pledging to "combat" it by 2030. In response, WHO drafted the Global Viral Hepatitis Strategy carrying the ambitious targets to reduce the number of deaths by two-thirds and to increase treatment rates up to 80%. Despite the availability of highly effective therapeutic regimens based on direct-acting antivirals many barriers to HCV eradication still remain. They are related to awareness of the infection, linkage to care, availability of the therapeutic drug regimens and reinfection. Overall, if an effective prophylactic vaccine will not be available, HCV eradication appears difficult to achieve in the future.
Topics: Antiviral Agents; Delivery of Health Care, Integrated; Disease Eradication; Global Health; Health Services Accessibility; Hepacivirus; Hepatitis C; Humans; Prevalence; Risk Factors; Time Factors; Treatment Outcome; Viral Hepatitis Vaccines
PubMed: 30472772
DOI: 10.1111/liv.14011 -
Ugeskrift For Laeger Nov 2021This review summarises the evolution of hepatitis C virus diagnostics over the past 30 years up to the present. A number of analyses have been used to select patients... (Review)
Review
This review summarises the evolution of hepatitis C virus diagnostics over the past 30 years up to the present. A number of analyses have been used to select patients for treatment or treatment for patients. In this aspect, HCV is a good story, since previously the diagnostics required extensive and expensive tests, but today two to three analyses are sufficient.
Topics: Hepacivirus; Hepatitis C; Humans
PubMed: 34796867
DOI: No ID Found -
Viruses Dec 2020Hepatitis C virus (HCV) is an important human pathogen with a high chronicity rate. An estimated 71 million people worldwide are living with chronic hepatitis C (CHC)... (Review)
Review
Hepatitis C virus (HCV) is an important human pathogen with a high chronicity rate. An estimated 71 million people worldwide are living with chronic hepatitis C (CHC) infection, which carries the risk of progression to hepatic fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Similar to other RNA viruses, HCV has a high rate of genetic variability generated by its high mutation rate and the actions of evolutionary forces over time. There are two levels of HCV genetic variability: intra-host variability, characterized by the distribution of HCV mutant genomes present in an infected individual, and inter-host variability, represented by the globally circulating viruses that give rise to different HCV genotypes and subtypes. HCV genetic diversity has important implications for virus persistence, pathogenesis, immune responses, transmission, and the development of successful vaccines and antiviral strategies. Here we will discuss how HCV genetic heterogeneity impacts viral spread and therapeutic control.
Topics: Antiviral Agents; Clinical Decision-Making; Disease Management; Drug Resistance, Viral; Genetic Variation; Genome, Viral; Genotype; Hepacivirus; Hepatitis C; Host-Pathogen Interactions; Humans; Quasispecies; RNA, Viral; Virus Replication
PubMed: 33383891
DOI: 10.3390/v13010041 -
World Journal of Gastroenterology Nov 2014Hepatitis C virus (HCV) infection represents an important public health problem worldwide. Reduction of HCV morbidity and mortality is a current challenge owned to... (Review)
Review
Hepatitis C virus (HCV) infection represents an important public health problem worldwide. Reduction of HCV morbidity and mortality is a current challenge owned to several viral and host factors. Virus molecular evolution plays an important role in HCV transmission, disease progression and therapy outcome. The high degree of genetic heterogeneity characteristic of HCV is a key element for the rapid adaptation of the intrahost viral population to different selection pressures (e.g., host immune responses and antiviral therapy). HCV molecular evolution is shaped by different mechanisms including a high mutation rate, genetic bottlenecks, genetic drift, recombination, temporal variations and compartmentalization. These evolutionary processes constantly rearrange the composition of the HCV intrahost population in a staging manner. Remarkable advances in the understanding of the molecular mechanism controlling HCV replication have facilitated the development of a plethora of direct-acting antiviral agents against HCV. As a result, superior sustained viral responses have been attained. The rapidly evolving field of anti-HCV therapy is expected to broad its landscape even further with newer, more potent antivirals, bringing us one step closer to the interferon-free era.
Topics: Animals; Antiviral Agents; Disease Progression; Drug Resistance, Viral; Drug Therapy, Combination; Evolution, Molecular; Genotype; Hepacivirus; Hepatitis C; Host-Pathogen Interactions; Humans; Phenotype; Treatment Outcome
PubMed: 25473152
DOI: 10.3748/wjg.v20.i43.15992 -
Journal of Hepatology Nov 2014Hepatitis C virus (HCV) is an important human pathogen that causes hepatitis, liver cirrhosis and hepatocellular carcinoma. It imposes a serious problem to public health... (Review)
Review
Hepatitis C virus (HCV) is an important human pathogen that causes hepatitis, liver cirrhosis and hepatocellular carcinoma. It imposes a serious problem to public health in the world as the population of chronically infected HCV patients who are at risk of progressive liver disease is projected to increase significantly in the next decades. However, the arrival of new antiviral molecules is progressively changing the landscape of hepatitis C treatment. The search for new anti-HCV therapies has also been a driving force to better understand how HCV interacts with its host, and major progresses have been made on the various steps of the HCV life cycle. Here, we review the most recent advances in the fast growing knowledge on HCV life cycle and interaction with host factors and pathways.
Topics: Cell Biology; Hepacivirus; Hepatitis C; Hepatocytes; Humans; Life Cycle Stages; Lipid Metabolism; RNA, Viral; Virology; Virus Replication
PubMed: 25443344
DOI: 10.1016/j.jhep.2014.06.031 -
World Journal of Gastroenterology Jan 2016About 130-170 million people, is estimated to be infected with the hepatitis C virus (HCV). Chronic HCV infection is one of the leading causes of liver-related death and... (Review)
Review
About 130-170 million people, is estimated to be infected with the hepatitis C virus (HCV). Chronic HCV infection is one of the leading causes of liver-related death and in many countries it is the primary reason for having a liver transplant. The main aim of antiviral treatment is to eradicate the virus. Until a few years ago the only treatment strategy was based on the combination of pegylated interferon and ribavirin (PEG/RBV). However, in genotypes 1 and 4 the rates of viral response did not surpass 50%, reaching up to 80% in the rest. In 2011 approval was given for the first direct acting antiviral agents (DAA), boceprevir and telaprevir, for treatment of genotype 1, in combination with traditional dual therapy. This strategy managed to increase the rates of sustained viral response (SVR) in both naive patients and in retreated patients, but with greater toxicity, interactions and cost, as well as being less safe in patients with advanced disease, in whom this treatment can trigger decompensation or even death. The recent, accelerated incorporation since 2013 of new more effective DAA, with pan-genomic properties and excellent tolerance, besides increasing the rates of SVR (even up to 100%), has also created a new scenario: shorter therapies, less toxicity and regimens free of PEG/RBV. This has enabled their almost generalised applicability in all patients. However, it should be noted that most of the scientific evidence available is based on expert opinion, case-control series, cohort studies and phase 2 and 3 trials, some with a reduced number of patients and select groups. Few data are currently available about the use of these drugs in daily clinical practice, particularly in relation to the appearance of side effects and interactions with other drugs, or their use in special populations or persons with the less common genotypes. This situation suggests the need for the generalised implementation of registries of patients receiving antiviral therapy. The main inconvenience of these new drugs is their high cost. This necessitates selection and prioritization of candidate patients to receive them, via strategies established by the various national organs, in accordance with the recommendations of scientific societies.
Topics: Antiviral Agents; Drug Resistance, Viral; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C; Humans; Phenotype; Treatment Outcome
PubMed: 26819511
DOI: 10.3748/wjg.v22.i4.1421 -
World Journal of Gastroenterology Aug 2014Despite the great successes achieved in the fields of virology and diagnostics, several difficulties affect improvements in hepatitis C virus (HCV) infection control and... (Review)
Review
Despite the great successes achieved in the fields of virology and diagnostics, several difficulties affect improvements in hepatitis C virus (HCV) infection control and eradication in the new era. New HCV infections still occur, especially in some of the poorest regions of the world, where HCV is endemic and long-term sequelae have a growing economic and health burden. An HCV vaccine is still no available, despite years of researches and discoveries about the natural history of infection and host-virus interactions: several HCV vaccine candidates have been developed in the last years, targeting different HCV antigens or using alternative delivery systems, but viral variability and adaption ability constitute major challenges for vaccine development. Many new antiviral drugs for HCV therapy are in preclinical or early clinical development, but different limitations affect treatment validity. Treatment predictors are important tools, as they provide some guidance for the management of therapy in patients with chronic HCV infection: in particular, the role of host genomics in HCV infection outcomes in the new era of direct-acting antivirals may evolve for new therapeutic targets, representing a chance for modulated and personalized treatment management, when also very potent therapies will be available. In the present review we discuss the most recent data about HCV epidemiology, the new perspectives for the prevention of HCV infection and the most recent evidence regarding HCV diagnosis, therapy and predictors of response to it.
Topics: Antiviral Agents; Developing Countries; Disease Progression; Drug Resistance, Viral; Endemic Diseases; Genotype; Hepacivirus; Hepatitis C; Host-Pathogen Interactions; Humans; Pharmacogenetics; Predictive Value of Tests; Risk Factors; Treatment Outcome
PubMed: 25110404
DOI: 10.3748/wjg.v20.i29.9633 -
Current Opinion in HIV and AIDS May 2017Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and HIV-HBV and HCV coinfection are major causes of chronic liver disease worldwide. Testing and... (Review)
Review
PURPOSE OF REVIEW
Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and HIV-HBV and HCV coinfection are major causes of chronic liver disease worldwide. Testing and diagnosis is the gateway for access to both treatment and prevention services, but there remains a large burden of undiagnosed infection globally. We review the global epidemiology, key challenges in the current hepatitis testing response, new tools to support the hepatitis global response (2016-2020 Global Hepatitis Health Sector strategy, and 2017 WHO guidelines on hepatitis testing) and future directions and innovations in hepatitis diagnostics.
RECENT FINDINGS
Key challenges in the current hepatitis testing response include lack of quality-assured serological and low-cost virological in-vitro diagnostics, limited facilities for testing, inadequate data to guide country-specific hepatitis testing approaches, stigmatization of those with or at risk of viral hepatitis and lack of guidelines on hepatitis testing for resource-limited settings. The new Global Hepatitis Health Sector strategy sets out goals for elimination of viral hepatitis as a public health threat by 2030 and gives outcome targets for reductions in new infections and mortality, as well as service delivery targets that include testing, diagnosis and treatment. The 2017 WHO hepatitis testing guidelines for adults, adolescents and children in low-income and middle-income countries outline the public health approach to strengthen and expand current testing practices for viral hepatitis and addresses who to test (testing approaches), which serological and virological assays to use (testing strategies) as well as interventions to promote linkage to prevention and care.
SUMMARY
Future directions and innovations in hepatitis testing include strategies to improve access such as through use of existing facility and community-based testing opportunities for hepatitis testing, near-patient or point-of-care assays for virological markers (nucleic acid testing and HCV core antigen), dried blood spot specimens used with different serological and nucleic acid test assays, multiplex and multi-disease platforms to enable testing for multiple analytes/pathogens and potential self-testing for viral hepatitis.
Topics: Global Health; Hepacivirus; Hepatitis C; Humans; Point-of-Care Systems
PubMed: 28306597
DOI: 10.1097/COH.0000000000000370