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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 -
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 -
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 -
Genes and Immunity May 2019The infection with the hepatitis C virus (HCV) is an example of the translational research success. The reciprocal interactions between clinicians and scientists have... (Review)
Review
The infection with the hepatitis C virus (HCV) is an example of the translational research success. The reciprocal interactions between clinicians and scientists have allowed in 30 years the initiation of empirical treatments by interferon, the discovery of the virus, the development of serological and virological tools for diagnosis but also for prognosis (the non-invasive biochemical or morphological fibrosis tests, the predictors of the specific immune response including genetic IL28B polymorphisms). Finally, well-tolerated and effective treatments with oral antivirals inhibiting HCV non-structural viral proteins involved in viral replication have been marketed this last decade, allowing the cure of all infected subjects. HCV chronic infection, which is a public health issue, is a hepatic disease, which may lead to a cirrhosis and an hepatocellular carcinoma (HCC) but also a systemic disease with extra-hepatic manifestations either associated with a cryoglobulinemic vasculitis or chronic inflammation. The HCV infection is the only chronic viral infection, which may be cured: the so-called sustained virologic response, defined by undetectable HCV RNA 12 weeks after the end of the treatment, significantly reduces the risk of morbidity and mortality associated with hepatic and extra-hepatic manifestations, which are mainly reversible. The history of HCV ends with the pangenotypic efficacy of the multiple combinations, easy to use for 8-12 weeks with one to three pills per day and little problems of tolerance. This explains the short 30 years from the virus discovery to the viral hepatitis elimination policy proposed by the World Health Organization (WHO) in 2016.
Topics: Animals; Hepacivirus; Hepatitis C; Humans
PubMed: 31019253
DOI: 10.1038/s41435-019-0066-z -
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 -
Infectious Disease Clinics of North... Sep 2000In the latter half of the 20th century, HCV emerged as the most common cause of chronic liver disease, and will likely remain so. Since its initial discovery in 1989,... (Review)
Review
In the latter half of the 20th century, HCV emerged as the most common cause of chronic liver disease, and will likely remain so. Since its initial discovery in 1989, rapid progress has been made in our understanding of the virology, epidemiology, natural history, diagnosis, and treatment of HCV. Over the next few decades, as further advancements are made, superior treatment options will become available.
Topics: Antiviral Agents; Diagnosis, Differential; Hepacivirus; Hepatitis C; Hepatitis C Antibodies; Humans; Prevalence
PubMed: 10987114
DOI: 10.1016/s0891-5520(05)70125-2 -
The Netherlands Journal of Medicine Aug 1992Until recently the diagnosis of non-A, non-B hepatitis was made by excluding other detectable viral infections of the liver. Progress in molecular biology made it... (Review)
Review
Until recently the diagnosis of non-A, non-B hepatitis was made by excluding other detectable viral infections of the liver. Progress in molecular biology made it possible to develop assays which can trace antibodies against the hepatitis C virus. This virus plays a major role in the pathogenesis of transfusion-related and sporadic non-A, non-B hepatitis and possibly of other liver diseases. Although the genome of a few isolates of the hepatitis C virus has already been decoded, the viral particles have not yet been visualized.
Topics: Genome, Viral; Hepacivirus; Hepatitis Antibodies; Hepatitis C; Hepatitis C Antibodies; Humans; Polymerase Chain Reaction; Transfusion Reaction
PubMed: 1383840
DOI: No ID Found