scholarly journals Simplification of Care for Chronic Hepatitis C Virus Infection

2020 ◽  
Vol 40 (04) ◽  
pp. 392-402 ◽  
Author(s):  
Jean-Michel Pawlotsky ◽  
Christian B. Ramers ◽  
John F. Dillon ◽  
Jordan J. Feld ◽  
Jeffrey V. Lazarus
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Scale Up ◽  
Linkage To Care ◽  
World Health ◽  
Direct Acting Antiviral ◽  
Hcv Screening ◽  
Health Organization ◽  
Chronic Hcv ◽  
Direct Acting

AbstractIn 2016, the World Health Organization (WHO) set a target for eliminating viral hepatitis as a major public health threat by 2030. However, while today's highly effective and well-tolerated pangenotypic direct-acting antiviral regimens have maximized simplification of hepatitis C virus (HCV) treatment, there remain a plethora of barriers to HCV screening, diagnosis, and linkage to care. As of 2017, only 19% of the estimated 71 million individuals living with chronic HCV worldwide were diagnosed and in 2015 to 2016, only 21% of diagnosed individuals had accessed treatment. Simplification and decentralization of the HCV care cascade would bolster patient engagement and support the considerable scale-up needed to achieve WHO targets. Recent developments in HCV screening and diagnosis, together with reduced pretreatment assessment and on-treatment monitoring requirements, can further streamline the care continuum, ensuring patients are linked to care quickly and earlier in the disease course, and minimize clinic visits.

scholarly journals Protocol: Prospective observational study aiming for micro-elimination of hepatitis C virus in Nagawa town: The Nagawa Project

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256711
Author(s):  
Hiroyuki Kobayashi ◽  
Satoru Joshita ◽  
Yuki Akahane ◽  
Katsuhiko Matsuzaki ◽  
Hiromi Yamada ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Observational Study ◽  
Antiviral Treatment ◽  
Protein Glycosylation ◽  
World Health ◽  
Hcv Rna ◽  
Care Needs ◽  
Direct Acting Antiviral ◽  
Health Organization

Background The World Health Organization has set a goal of hepatitis C virus (HCV) elimination by the year 2030. However, no regions in Japan have succeeded in eradicating HCV. Micro-elimination is an approach to attain hepatitis C eradication in which national eradication goals are applied to specific populations so that viral treatment and control efforts can move forward quickly and efficiently. In order to eradicate HCV from Japan, this study aims to achieve HCV micro-elimination in the town of Nagawa. Methods and design The Nagawa Project is an ongoing, prospective, multiple-institution, observational study running from April 1, 2021, to March 31, 2024. All residents of Nagawa town, excluding those under 20 years of age, not consenting to the study, or unable to undergo health check-ups due to nursing care needs, will be included. If found to be HCV antibody-positive, the participant will be recommended to see a doctor in consideration of MAC-2 binding protein glycosylation isomer values. Then, the participant will undergo serum HCV RNA measurement with the real-time polymerase chain reaction by an attending physician. If the participant is HCV RNA-positive, he or she will be referred to a hepatologist for further evaluation. In the case of a definitive diagnosis of chronic hepatitis C, direct acting antiviral treatment will be initiated. Through this process, HCV will be systematically micro-eliminated from the region. Discussion The Nagawa Project will reveal the prevalence of chronic HCV in addition to the HCV eradication rate in Nagawa town towards achieving HCV micro-elimination. Trial registration This study is performed by Shinshu University School of Medicine and was registered as UMIN 000044114 on May 6, 2021.

scholarly journals Sa1525 – Visne Analysis of Hepatitis C Virus-Specific Cd8 T Cells from Direct Acting Antiviral-Treated Chronic Hcv Patients and Hcv Resolvers

2019 ◽  
Vol 156 (6) ◽  
pp. S-1232
Author(s):  
Jihad Aljabban ◽  
Pierre Tonnerre ◽  
Dan Kvistad ◽  
Max Robidoux ◽  
Joelle Brown ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cd8 T Cells ◽  
Direct Acting Antiviral ◽  
Chronic Hcv ◽  
Direct Acting

scholarly journals Agent-based modeling of persons who inject drugs in metropolitan Chicago suggests that re-treatment with antivirals of persons who are re-infected with Hep C is critical to achieve the WHO incidence reduction objective by 2030

2019 ◽  
Author(s):  
Eric Tatara ◽  
Alexander Gutfraind ◽  
Nicholson T. Collier ◽  
Scott J. Cotler ◽  
Marian Major ◽  
...  
Keyword(s):  
Scale Up ◽  
Treatment Strategies ◽  
Agent Based Modeling ◽  
World Health ◽  
Persons Who Inject Drugs ◽  
Agent Based ◽  
Direct Acting Antiviral ◽  
The World ◽  
Health Organization ◽  
Direct Acting

ABSTRACTHepatitis C (HCV) is a leading cause of chronic liver disease and mortality worldwide. Persons who inject drugs (PWID) are at the highest risk for acquiring and transmitting HCV infection. We developed an agent-based model (ABM) to identify and optimize direct-acting antiviral (DAA) therapy scale-up and treatment strategies for achieving the World Health Organization (WHO) goals of HCV elimination by the year 2030. DAA is highly efficacious, but may require re-treatment particularly among PWID who at risk for reinfection after cure. Using an ABM approach, we predict that this prohibition will jeopardize achieving the WHO’s goal of reducing 90% of HCV incidence by 2030. We found that DAA scale-up rates of greater than or equal to 5% per year can achieve the WHO target of 90% incidence reduction. Our model simulations underscore the importance of DAA scale-up that includes re-treatment of re-infected individuals in order to achieve significant reductions in incidence.FUNDINGThis research is supported by NIH grant R01GM121600.

scholarly journals Immunological Mechanisms for Hepatocellular Carcinoma Risk after Direct-Acting Antiviral Treatment of Hepatitis C Virus Infection

2021 ◽  
Vol 10 (2) ◽  
pp. 221
Author(s):  
Pil Soo Sung ◽  
Eui-Cheol Shin
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
De Novo ◽  
Hcv Infection ◽  
Direct Acting Antiviral ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Direct Acting

Direct-acting antiviral agents (DAAs) that allow for rapid clearance of hepatitis C virus (HCV) may evoke immunological changes. Some cases of rapid de novo hepatocellular carcinoma (HCC) development or early recurrence of HCC after DAA treatment have been reported. During chronic HCV infection, natural killer (NK) cells exhibited a deviant functional phenotype with decreased production of antiviral cytokines and increased cytotoxicity; however, DAA treatment rapidly decreased their cytotoxic function. Effective DAA therapy also suppressed the intrahepatic activation of macrophages/monocytes. This was followed by a decrease in mucosal-associated invariant T (MAIT) cell cytotoxicity without normalization of cytokine production. Rapid changes in the phenotypes of NK and MAIT cells after DAA treatment may attenuate the cytotoxicity of these cells against cancer cells. Moreover, DAA treatment did not normalize the increased frequencies of regulatory T cells even after clearance of HCV infection. Thus, the persistently increased frequency of regulatory T cells may contribute to a local immunosuppressive milieu and hamper the clearance of cancer cells. This review will focus on recent studies describing the changes in innate and adaptive immune responses after DAA treatment in patients with chronic HCV infection in the context of de novo occurrence or recurrence of HCC.

scholarly journals Safety and efficacy of sofosbuvir based regimen in the treatment of hepatitis C virus infection among hemodialysis patients in Morocco

2021 ◽  
Vol 5 (3) ◽  
pp. 077-080
Author(s):  
Tamzaourte Mouna ◽  
Zajjari Yassir ◽  
Berrag Sanae ◽  
Adioui Tarik ◽  
Aourarh Aziz ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Side Effects ◽  
Treatment Options ◽  
Hemodialysis Patients ◽  
Direct Acting Antiviral ◽  
Treatment Regimens ◽  
Patient Reported ◽  
Chronic Hcv ◽  
Direct Acting

The introduction of a new class of drugs known as direct acting antiviral (DAA) agents represents a revolution in the treatment of hepatitis C virus (HCV) in the general population, as these regimens are associated with higher sustained virological response (SVR) rates and fewer side effects. However, for patients with advanced chronic kidney disease suffering from HVC infection, treatment options including DAA remain limited. The aim of this study is to report our experience on Sofosbuvir (SOF) based regimen in the treatment of HCV in hemodialysis patients. In this observational study, we included all patients with chronic HCV infection on hemodialysis who were treated with SOF in our Hospital between April 2016 and March 2018. All patients were treated with a combination of 400 mg of SOF three times a week after hemodialysis and of 60 mg of Daclatasvir daily for a total of 12 to 24 weeks. A total of 20 hemodialysis patients were included in this study. 12 were females and the mean age was 52.1 ± 15.5 years. 11 patients were infected with HCV genotypes 1b. All patients achieved SVR. Clinical and biological tolerance was very good for all patients and none of them had to discontinue treatment because of side effects or developed hepatobiliary and cardiac toxicity. Two patients reported fatigue and another patient reported headaches. However, these symptoms were spontaneously resolved after the end of the treatment. In Morocco, despite the absence of new DAA combination treatment regimens which are not renally eliminated, our study concludes that SOF based treatment without Ribavirin or Peginterferon was effective and safe with minimal side effects. However, larger studies are still needed in order to validate these results.

scholarly journals A hepatitis C-vírus (HCV) három évtizede a felfedezéstől a globális elimináció lehetőségéig: a transzlációs kutatás sikere

2018 ◽  
Vol 159 (12) ◽  
pp. 455-465 ◽  
Author(s):  
Alajos Pár ◽  
Gabriella Pár
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Health Sector ◽  
World Health ◽  
Direct Acting Antivirals ◽  
Treatment Plans ◽  
Health Organization ◽  
Direct Acting ◽  
Evidence Based Guidelines

Abstract: More than 25 years after the discovery of hepatitis C virus, the development of the direct acting antivirals can lead to the regional or long-term global elimination of the virus with over 90% efficacy. This is the success of basic and clinical translational research. Yet, some unsolved challanges remain, such as the great number of unidentified patients who are not aware of their condition, the limited access to the therapy due to the high prices of the drugs, and the treatment of resistance-associated variants. In addition, the lack of vaccine is also an obstacle. In 2016, the World Health Organization (WHO) developed the first global health sector strategy for the elimination of viral hepatitis by 2030. Its evidence-based guidelines are primarily targeted at the national hepatitis programme managers who are responsible for the national testing and treatment plans. According to these recommendations, it is of basic importance to perform focused risk-based testing in higher-risk populations and after diagnosis to start treatment as “cure as prevention”, furthermore, to limit the risk of reinfection. We review the events of the HCV story from the discovery to these days, including virology, epidemiology, pathogenesis, diagnosis and therapy. Orv Hetil. 2018; 159(12): 455–465.

scholarly journals In VitroActivity and Resistance Profile of Samatasvir, a Novel NS5A Replication Inhibitor of Hepatitis C Virus

2014 ◽  
Vol 58 (8) ◽  
pp. 4431-4442 ◽  
Author(s):  
J. P. Bilello ◽  
L. B. Lallos ◽  
J. F. McCarville ◽  
M. La Colla ◽  
I. Serra ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Resistance Profile ◽  
Direct Acting Antiviral ◽  
Genotype 1A ◽  
Hcv Protease ◽  
Chronic Hcv ◽  
Direct Acting

ABSTRACTThe hepatitis C virus (HCV) nonstructural 5A (NS5A) protein is a clinically validated target for drugs designed to treat chronic HCV infection. This study evaluated thein vitroactivity, selectivity, and resistance profile of a novel anti-HCV compound, samatasvir (IDX719), alone and in combination with other antiviral agents. Samatasvir was effective and selective against infectious HCV and replicons, with 50% effective concentrations (EC50s) falling within a tight range of 2 to 24 pM in genotype 1 through 5 replicons and with a 10-fold EC50shift in the presence of 40% human serum in the genotype 1b replicon. The EC90/EC50ratio was low (2.6). A 50% cytotoxic concentration (CC50) of >100 μM provided a selectivity index of >5 × 107. Resistance selection experiments (with genotype 1a replicons) and testing against replicons bearing site-directed mutations (with genotype 1a and 1b replicons) identified NS5A amino acids 28, 30, 31, 32, and 93 as potential resistance loci, suggesting that samatasvir affects NS5A function. Samatasvir demonstrated an overall additive effect when combined with interferon alfa (IFN-α), ribavirin, representative HCV protease, and nonnucleoside polymerase inhibitors or the nucleotide prodrug IDX184. Samatasvir retained full activity in the presence of HIV and hepatitis B virus (HBV) antivirals and was not cross-resistant with HCV protease, nucleotide, and nonnucleoside polymerase inhibitor classes. Thus, samatasvir is a selective low-picomolar inhibitor of HCV replicationin vitroand is a promising candidate for future combination therapies with other direct-acting antiviral drugs in HCV-infected patients.

scholarly journals 2899. Decreased Hepatitis C Virus-Associated Mortality in the US 2014–2017 After New Oral Direct-Acting Antiviral Era

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S82-S83
Author(s):  
Zainab Wasti ◽  
Dagan Coppock ◽  
Edgar Chou ◽  
Dong Heun Lee
Keyword(s):  
United States ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Linkage To Care ◽  
The United States ◽  
Ease Of Use ◽  
Hcv Infection ◽  
Race And Gender ◽  
Direct Acting Antiviral ◽  
Direct Acting

Abstract Background Due to the ease of use and low side effect profile of new direct-acting antivirals (DAA), cure rates for hepatitis C virus (HCV) infection have increased in recent years. However, limited data exist addressing the mortality associated with HCV infection since the advent of DAAs. This study examines multiple-cause-of-death (MCOD) data from 2014 to 2017 to describe changes in HCV-associated mortality in the United States. Methods We examined death certificate information from public use MCOD data obtained from the National Center for Health Statistics. All-cause mortality associated with HCV, as defined by ICD-10 codes (B17.1 and B18.2), was evaluated. The age-adjusted crude mortality rate was calculated. Overall HCV-associated mortality, stratified by race and gender, was analyzed. Results From 2014 to 2017, the number of deaths associated with HCV, as listed in death certificates decreased from 19,613 to 17,253. This represents an average of 4% decrease in mortality each year. Crude age-adjusted mortality decreased from 5.01 (95% CI 4.93–5.08) deaths per 100,000 people in 2014 to 4.13 (95% CI 4.07–4.20) deaths per 100,000 people in 2017. Males had age-adjusted mortality of 6.82 (95% CI 6.76–6.88) and females had age-adjusted mortality of 2.59 (95% CI 2.55–2.63). African Americans had age-adjusted mortality of 7.50 (95% CI 7.37–7.63), and whites had age-adjusted mortality of 4.39 (95% CI 4.35–4.42) during the three-year period. Conclusion After the introduction of DAAs in 2014, mortality associated with HCV significantly decreased in the United States. There were differences in mortality rates by gender and race, which may reflect differences in HCV seroprevalence. With the availability of effective, well-tolerated HCV treatment, aggressive HCV screening and linkage to care is warranted, especially in high-risk populations. Disclosures All Authors: No reported Disclosures.

scholarly journals Liver cT1 decreases following direct-acting antiviral therapy in patients with chronic hepatitis C virus

2020 ◽  
Author(s):  
Arjun N. A. Jayaswal ◽  
Christina Levick ◽  
Jane Collier ◽  
Elizabeth M. Tunnicliffe ◽  
Matthew D. Kelly ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Liver Fibrosis ◽  
Liver Fat ◽  
Liver Ct ◽  
Direct Acting Antiviral ◽  
Chronic Hepatitis C Virus ◽  
Chronic Hcv ◽  
Direct Acting

Abstract Purpose Direct-acting antiviral therapies (DAAs) for treatment of chronic hepatitis C virus (HCV) have excellent rates of viral eradication, but their effect on regression of liver fibrosis is unclear. The primary aim was to use magnetic resonance imaging (MRI) and spectroscopy (MRS) to evaluate changes in liver fibrosis, liver fat and liver iron content (LIC) in patients with chronic HCV following treatment with DAAs. Methods In this prospective study, 15 patients with chronic HCV due to start treatment with DAAs and with transient elastography (TE) > 8 kPa were recruited consecutively. Patients underwent MRI and MRS at baseline (before treatment), and at 24 weeks and 48 weeks after the end of treatment (EoT) for the measurement of liver cT1 (fibroinflammation), liver fat and T2* (LIC). Results All patients achieved a sustained virological response. Liver cT1 showed significant decreases from baseline to 24 weeks post EoT (876 vs 806 ms, p = 0.002, n = 15), baseline to 48 weeks post EoT (876 vs 788 ms, p = 0.0002, n = 13) and 24 weeks post EoT to 48 weeks post EoT (806 vs 788 ms, p = 0.016, n = 13). Between baseline and 48 weeks EoT significant reduction in liver fat (5.17% vs 2.65%, p = 0.027) and an increase in reported LIC (0.913 vs 0.950 mg/g, p = 0.021) was observed. Conclusion Liver cT1 decreases in patients with chronic HCV undergoing successful DAA treatment. The relatively fast reduction in cT1 suggests a reduction in inflammation rather than regression of fibrosis.

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