Hepatitis C New Drugs Review
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Noninvasive Assessment of Fibrosis Regression in Hepatitis C Virus Sustained Virologic Responders

Noninvasive Assessment of Fibrosis Regression in Hepatitis C Virus Sustained Virologic Responders | Hepatitis C New Drugs Review | Scoop.it
The emergence of direct-acting antiviral (DAA) therapies and noninvasive measures of liver fibrosis has streamlined the management of patients with chronic hepatitis C virus (HCV) infection. DAA therapy is associated with a significantly higher rate o
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Hepatitis C New Drugs Review
FDA approved Incivek(telaprevir, Vertex) on Monday 23 May by its PDUFA deadline.A paradigm shift in the treatment of Hepatitis C virus infection. <a href="http://knol.google.com/k/krishan-maggon/boceprevir-merck-telaprevir-vertex/3fy5eowy8suq3/151#"; rel="nofollow">http://knol.google.com/k/krishan-maggon/boceprevir-merck-telaprevir-vertex/3fy5eowy8suq3/151#</a>;
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Created public version #121 of the knol: "Boceprevir (Merck) & Telaprevir (Vertex) Hepatitis C : FDA Review & Approval"

Created public version #121 of the knol: "Boceprevir (Merck) & Telaprevir (Vertex) Hepatitis C : FDA Review & Approval" | Hepatitis C New Drugs Review | Scoop.it
Krishan Maggon published version 121 of a knol titled: "Boceprevir (Merck) & Telaprevir (Vertex) Hepatitis C : FDA Review & Approval"...
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Sofosbuvir/velpatasvir for 12 weeks in genotype 1–4 HCV-infected liver transplant recipients

Sofosbuvir/velpatasvir for 12 weeks in genotype 1–4 HCV-infected liver transplant recipients | Hepatitis C New Drugs Review | Scoop.it
Among HCV-infected liver transplant recipients, HCV recurrence emerges in nearly all patients.1 Within five years post-transplant, cirrhosis related to HCV ensues in approximately 30% of patients with recurrent, chronic HCV infection and is associated with increased graft loss rates and death.2–5...
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A serum protein factor mediates maturation and apoB-association of HCV particles in the extracellular milieu

A serum protein factor mediates maturation and apoB-association of HCV particles in the extracellular milieu | Hepatitis C New Drugs Review | Scoop.it
Hepatitis C virus (HCV) infection is a major cause of chronic liver diseases worldwide.
Although recent direct antiviral agents (DAA) can now cure most patients, it remains
major challenges in basic, translational and clinical research[1].
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Superior In vivo Transduction of Human Hepatocytes Using Engineered AAV3 Capsid

Superior In vivo Transduction of Human Hepatocytes Using Engineered AAV3 Capsid | Hepatitis C New Drugs Review | Scoop.it
Adeno-associated viral (AAV) vectors are currently being tested in multiple clinical
trials for liver-directed gene transfer to treat the bleeding disorders hemophilia
A and B and metabolic disorders.
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Treatment with direct–acting antivirals for HCV decreases but does not eliminate the risk of hepatocellular carcinoma - Piñero - - Liver International - Wiley Online Library

Treatment with direct–acting antivirals for HCV decreases but does not eliminate the risk of hepatocellular carcinoma - Piñero - - Liver International - Wiley Online Library | Hepatitis C New Drugs Review | Scoop.it
Background & Aims Data from Europe and North America have been published regarding the risk of developing hepatocellular carcinoma (HCC) after treatment with direct antiviral agents (DAA). We proposed to evaluate cumulative incidence and associated risk factors for de novo HCC. Methods This was a prospective multicenter cohort study from Latin America including 1,400 F1‐F4 treated patients with DAAs (F3‐F4 n=1017). Cox proportional regression models (hazard ratios, HR and 95% CI) were used to evaluate independent associated variables with HCC. Further adjustment with competing risk regression and propensity score matching was carried out. Results During a median follow‐up of 16 months (IQR 8.9‐23.4 months) since DAAs initiation, overall cumulative incidence of HCC was 0.02 (CI 0.01;0.03) at 12 months and 0.04 (CI 0.03;0.06) at 24 months. Cumulative incidence of HCC in cirrhotic patients (n=784) was 0.03 (CI 0.02‐0.05) at 12 months and 0.06 (CI 0.04‐0.08) at 24 months of follow‐up. Failure to achieve SVR was independently associated with de novo HCC with a HR of 4.9 (CI 1.44;17.32), after adjusting for diabetes mellitus, previous interferon non‐responder, Child Pugh and clinically significant portal hypertension. SVR presented an overall relative risk reduction for de novo HCC of 73% (CI 15%‐91%), 17 patients were needed to be treated to prevent one case of de novo HCC in this cohort. Conclusions Achieving SVR with DAAs regimens was associated with a significant risk reduction of HCC. However, this risk remained high in patients with advanced fibrosis, thus demanding continuous surveillance strategies in this population. This article is protected by copyright. All rights reserved.
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Ascletis and Alphamab announce strategic collaboration and licensing agreement for anti-PD-L1 to treat hepatitis B and other viral diseases

Ascletis and Alphamab announce strategic collaboration and licensing agreement for anti-PD-L1 to treat hepatitis B and other viral diseases | Hepatitis C New Drugs Review | Scoop.it
KN035 is an investigational programmed cell death ligand-1 (PD-L1) monoclonal antibody which has been exposed to more than 500 patients in multiple clinical trials in US, China and...
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Hepatitis C virus-associated hepatocellular carcinoma after sustained virologic response

Hepatitis C virus-associated hepatocellular carcinoma after sustained virologic response | Hepatitis C New Drugs Review | Scoop.it
Abstract
The introduction of a direct-acting antiviral (DAA) for patients with hepatitis C virus (HCV) infection, could lead to higher sustained virologic response (SVR) rates with fewer adverse events, and it could shorten the treatment duration relative to the interferon era. Although most recent clinical studies have demonstrated that the occurrence rates of hepatocellular carcinoma (HCC) are decreased by SVR with both interferon-based and interferon-free-regimens, there are several reports about the unexpected observation of high rates of early tumor occurrence and recurrence in patients with HCV-related HCC undergoing interferon-free therapy despite SVR. Several mechanisms of HCC occurrence and rapid immunological changes, including cytokines and chemokines during and after DAA treatment, have also been reported. We focused on the possibilities that HCC occurs or recurs during and after DAA treatment, based on the reported clinical and basic studies. Further studies and observations will be needed to determine the short-term and long-term effects on hepatocarcinogenesis caused by the eradication of HCV with DAAs. New serum biomarkers and a follow-up system for HCV-patients with SVR should be established.

Keywords: Hepatitis C virus, Hepatocellular carcinoma, Sustained virologic response, Direct-acting antiviral agents
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Simultaneous Quantification of Hepatitis C Virus Envelope Glycoproteins E1 and E2 by Dual-Color Fluorescence Immunoblot Analysis

Simultaneous Quantification of Hepatitis C Virus Envelope Glycoproteins E1 and E2 by Dual-Color Fluorescence Immunoblot Analysis | Hepatitis C New Drugs Review | Scoop.it
Abstract
The hepatitis C virus (HCV) envelope glycoproteins, E1 and E2, are crucial for HCV assembly and entry, and are promising vaccine antigens. However, they are challenging to study because of technical difficulties in protein production and in quality control for protein folding and glycosylation. To study E1 and E2 in different experimental systems, e.g. infected cells, virus culture, virus-like particles, and clinical samples, a standardized method to accurately quantify the glycoproteins will be essential for most research projects. Here we outline a sensitive assay based on dual-color fluorescence immunoblot and the Odyssey imaging system to detect and quantify HCV E1 and E2 glycoproteins either using a purified E1E2 complex, or an engineered protein standard containing E1 and E2 at equal molar ratio. The method is capable of simultaneously detecting and quantifying as little as 7 ng of E1 and 5 ng of E2 in HCV pseudoparticles, and will be useful to quantify E1 and E2 from a wide variety of samples.

Key words
E1 E2 Glycoprotein Immunoblot Protein standard Antibody 
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Hepatitis C | Roche Molecular

Hepatitis C | Roche Molecular | Hepatitis C New Drugs Review | Scoop.it
Find out more about the critical importance of detecting, differentiating, and monitoring viral load in patients with the hepatitis C virus (HCV)....
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Genetic and structural insights into broad neutralization of hepatitis C virus by human VH1-69 antibodies. - PubMed - NCBI

Genetic and structural insights into broad neutralization of hepatitis C virus by human VH1-69 antibodies. - PubMed - NCBI | Hepatitis C New Drugs Review | Scoop.it
Abstract
An effective vaccine to the antigenically diverse hepatitis C virus (HCV) must target conserved immune epitopes. Here, we investigate cross-neutralization of HCV genotypes by broadly neutralizing antibodies (bNAbs) encoded by the relatively abundant human gene family V H 1-69. We have deciphered the molecular requirements for cross-neutralization by this unique class of human antibodies from crystal structures of HCV E2 in complex with bNAbs. An unusually high binding affinity is found for germ line-reverted versions of VH1-69 precursor antibodies, and neutralization breadth is acquired during affinity maturation. Deep sequencing analysis of an HCV-immune B cell repertoire further demonstrates the importance of the V H 1-69 gene family in the generation of HCV bNAbs. This study therefore provides critical insights into immune recognition of HCV with important implications for rational vaccine design.

PMID: 30613781 PMCID: PMC6314831 DOI: 10.1126/sciadv.aav1882
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Hepatitis C virus protein interaction network for HCV clearance and association of DAA to HCC occurrence via data mining approach: A systematic review and critical analysis - Sghaier - - Reviews in...

Summary
HCV has been associated with pro‐inflammatory state, which predisposes to liver cancer such as hepatocellular carcinoma (HCC). However, the different molecular mechanisms underlying the effect of HCV infection on the HCC progression have remained unclear. Although HCV infection illustrates the role of host genetics in the outcome of infectious diseases, there is no clear overview of some single nucleotide polymorphisms (SNPs) influencing spontaneous or treatment‐induced HCV eradication.

In the present study, we studied the possible role of HCV infection in the processes of HCC initiation, and we performed a systemic analysis using data mining approaches to identify host polymorphisms associated with treatment response and HCC development using topological analysis of protein‐proteins interactions (PPI) networks.

On the basis of our analysis performed, we identify the key hub proteins related to HCV‐treatment response infection and HCC development too. A handful host genetics polymorphisms such as inosine triphosphatase (ITPA), interferon, lambda 3 (IFNL3), interferon, lambda 4 (IFNL4), toll‐like receptors (TLRs), interferon‐stimulated gene 15 (ISG‐15) … were identified as key genes for treatment prediction and HCC evolution. Compared between unique genes for HCV‐treatment response and genes particular to HCV‐HCC development, we found a common PPI network that may participate in more extensive signalling process during anti‐HCV treatment, which can play important roles in modulating the immune response to the occurrence of HCC.

Data mining is effective tool for identifying potential regulators pathways involved in treatment response and HCC development. Our study may contribute to a better understanding of HCV immunopathogenesis and highlights the difficult role of host genetics in HCV clearance.
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Pharmacological interventions for acute hepatitis C infection - Kalafateli, M - 2018 | Cochrane Library

Pharmacological interventions for acute hepatitis C infection - Kalafateli, M - 2018 | Cochrane Library | Hepatitis C New Drugs Review | Scoop.it
Cochrane Database of Systematic Reviews Abstract Background Hepatitis C virus (HCV) is a single‐stranded RNA (ribonucleic acid) virus that has the potential to cause inflammation of the liver. The traditional definition of acute HCV infection is the first six months following infection with the virus. Another commonly used definition of acute HCV infection is the absence of HCV antibody and subsequent seroconversion (presence of HCV antibody in a person who was previously negative for HCV antibody). Approximately 40% to 95% of people with acute HCV infection develop chronic HCV infection, that is, have persistent HCV RNA in their blood. In 2010, an estimated 160 million people worldwide (2% to 3% of the world's population) had chronic HCV infection. The optimal pharmacological treatment of acute HCV remains controversial. Chronic HCV infection can damage the liver. Objectives To assess the comparative benefits and harms of different pharmacological interventions in the treatment of acute HCV infection through a network meta‐analysis and to generate rankings of the available pharmacological treatments according to their safety and efficacy. However, it was not possible to assess whether the potential effect modifiers were similar across different comparisons. Therefore, we did not perform the network meta‐analysis and instead we assessed the comparative benefits and harms of different interventions versus each other or versus no intervention using standard Cochrane methodology. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and randomised controlled trials registers to April 2016 to identify randomised clinical trials on pharmacological interventions for acute HCV infection. Selection criteria We included only randomised clinical trials (irrespective of language, blinding, or publication status) in participants with acute HCV infection. We excluded trials which included previously liver transplanted participants and those with other coexisting viral diseases. We considered any of the various pharmacological interventions compared with placebo or each other. Data collection and analysis We used standard methodological procedures expected by Cochrane. We calculated the odds ratio (OR) and rate ratio with 95% confidence intervals (CI) using both fixed‐effect and random‐effects models based on the available‐participant analysis with Review Manager 5. We assessed risk of bias according to Cochrane, controlled risk of random errors with Trial Sequential Analysis, and assessed the quality of the evidence using GRADE. Main results We identified 10 randomised clinical trials with 488 randomised participants that met our inclusion criteria. All the trials were at high risk of bias in one or more domains. Overall, the evidence for all the outcomes was very low quality evidence. Nine trials (467 participants) provided information for one or more outcomes. Three trials (99 participants) compared interferon‐alpha versus no intervention. Three trials (90 participants) compared interferon‐beta versus no intervention. One trial (21 participants) compared pegylated interferon‐alpha versus no intervention, but it did not provide any data for analysis. One trial (41 participants) compared MTH‐68/B vaccine versus no intervention. Two trials (237 participants) compared pegylated interferon‐alpha versus pegylated interferon‐alpha plus ribavirin. None of the trials compared direct‐acting antivirals versus placebo or other interventions. The mean or median follow‐up period in the trials ranged from six to 36 months. There was no short‐term mortality (less than one year) in any group in any trial except for one trial where one participant died in the pegylated interferon‐alpha plus ribavirin group (1/95: 1.1%). In the trials that reported follow‐up beyond one year, there were no further deaths. The number of serious adverse events was higher with pegylated interferon‐alpha plus ribavirin than with pegylated interferon‐alpha (rate ratio 2.74, 95% CI 1.40 to 5.33; participants = 237; trials = 2; I2 = 0%). The proportion of people with any adverse events was higher with interferon‐alpha and interferon‐beta compared with no intervention (OR 203.00, 95% CI 9.01 to 4574.81; participants = 33; trials = 1 and OR 27.88, 95% CI 1.48 to 526.12; participants = 40; trials = 1). None of the trials reported health‐related quality of life, liver transplantation, decompensated liver disease, cirrhosis, or hepatocellular carcinoma. The proportion of people with chronic HCV infection as indicated by the lack of sustained virological response was lower in the interferon‐alpha group versus no intervention (OR 0.27, 95% CI 0.09 to 0.76; participants = 99; trials = 3; I2 = 0%). The differences between the groups were imprecise or not estimable (because neither group had any events) for all the remaining comparisons. Four of the 10 trials (40%) received financial or other assistance from pharmaceutical companies who would benefit from the findings of the research; the source of funding was not available in five trials (50%), and one trial (10%) was funded by a hospital. Authors' conclusions Very low quality evidence suggests that interferon‐alpha may decrease the incidence of chronic HCV infection as measured by sustained virological response. However, the clinical impact such as improvement in health‐related quality of life, reduction in cirrhosis, decompensated liver disease, and liver transplantation has not been reported. It is also not clear whether this finding is applicable in the current clinical setting dominated by the use of pegylated interferons and direct‐acting antivirals, although we found no evidence to support that pegylated interferons or ribavirin or both are effective in people with acute HCV infection. We could find no randomised trials comparing direct‐acting antivirals with placebo or other interventions for acute HCV infection. There is significant uncertainty in the benefits and harms of the interventions, and high‐quality randomised clinical trials are required. Plain language summary Medical treatment of acute hepatitis C virus infection Background Hepatitis C virus (HCV) is a virus that affects the liver. It is usually transmitted by injectable drug abuse, transfusion of infected blood, unhygienic tattooing practices, coming into contact with blood infected with HCV, and unprotected sex. Acute HCV infection is the period that covers within six months of infection. While some people clear the virus after acute HCV infection, the virus remains in others. This is called chronic HCV infection and may cause major health problems such as excessive tiredness, and liver failure leading to vomiting blood, confusion, and death. Overall, an estimated 160 million people worldwide (2% to 3% of the world's population) have chronic HCV infection. A number of medical treatments have been used for acute HCV infection. The best way to treat acute HCV infection is not clear. We sought to resolve this issue by searching for existing studies on the topic. We included all randomised clinical trials (clinical studies where people are randomly put into one of two or more intervention groups) whose results were reported to April 2016. We included only trials in which participants had not undergone liver transplantation previously and those who did not have liver disease due to other viral infections. Apart from using standard Cochrane methods which allow comparison of only two interventions at a time (direct comparison), we planned to use advanced method which allows comparison of the many different interventions individually compared in the trials (network meta‐analysis). However, because of the nature of the information available, we could not determine whether the network meta‐analysis results were reliable. So, we used standard Cochrane methodology. Study characteristics We identified 10 randomised clinical trials which were eligible for our review. Nine randomised clinical trials (467 participants) provided information for one or more measures (outcomes). The main interventions compared included different forms of interferon (protein secreted in response to viral infection), namely, interferon‐alpha alone, interferon‐beta alone, pegylated interferon‐alpha alone, pegylated interferon‐alpha plus ribavirin (another antiviral drug), a vaccine called MTH‐68/B made from a different virus, versus no intervention. None of the trials compared direct‐acting antivirals (the latest option for treating HCV infection) versus placebo or other interventions. The average follow‐up period in the trials ranged from six months to three years. Source of funding Four of the 10 trials (40%) received financial or other assistance from pharmaceutical companies who would benefit from the findings of the research; the source of funding was not available in five trials (50%), and one trial (10%) was funded by a hospital. Quality of evidence All the trials were at high risk of bias, and the overall quality of the evidence was very low. This means that there is a possibility of making wrong conclusions overestimating benefits or underestimating harms of one intervention or the other because of the way that the trials were conducted. Key results No deaths occurred less than one year after treatment in any group in any trial except for one trial where one participant died in the pegylated interferon‐alpha plus ribavirin group (1/95: 1.1%). In the trials in which participants were followed up beyond one year, there were no further deaths. The number of serious complications was higher with pegylated interferon‐alpha plus ribavirin than with pegylated interferon‐alpha. The percentage of people with any complications was higher with interferon‐alpha and interferon‐beta than with no intervention. None of the trials reported health‐related quality of life, liver transplantation, liver failure, severe liver damage, or liver cancer. The percentage of people in whom the virus remained in the blood six months after the end of treatment was lower in the interferon‐alpha than in the no intervention groups. There was no evidence of differences between the groups for all the remaining comparisons. There is significant uncertainty about the size and direction of the results and high quality randomised clinical trials are required. Unlock the full review
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RCSB PDB - 6BKD: Structure of Hepatitis C Virus Envelope Glycoprotein E2 core from genotype 6a bound to broadly neutralizing antibody AR3D

RCSB PDB - 6BKD: Structure of Hepatitis C Virus Envelope Glycoprotein E2 core from genotype 6a bound to broadly neutralizing antibody AR3D | Hepatitis C New Drugs Review | Scoop.it
6BKD: Structure of Hepatitis C Virus Envelope Glycoprotein E2 core from genotype 6a bound to broadly neutralizing antibody AR3D...
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Hepatitis C Virus–Associated Fulminant Hepatic Failure | NEJM

Hepatitis C Virus–Associated Fulminant Hepatic Failure | NEJM | Hepatitis C New Drugs Review | Scoop.it
Although the temporal association between the acquisition of HCV infection and the development of fulminant hepatitis in this patient suggests that HCV was the causative agent, we cannot exclude the role of nonviral factors. Nevertheless, the incidence of post-transfusion fulminant hepatitis associated with major surgical operations is exceedingly low.27 Among more than 100 prospectively followed transfusion recipients in whom non-A, non-B hepatitis developed after major surgery, this patient was the only one in whom fulminant hepatitis developed.27 Thus, it is very unlikely that intraoperative factors were responsible for the fulminant hepatic failure.

In summary, HCV can cause fulminant hepatic failure. The disease is characterized by continuous viral replication. The detection of serum HCV RNA by PCR is the earliest and most valuable marker for the diagnosis of fulminant hepatitis C.
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Sustained virological response to hepatitis C treatment decreases the incidence of complications associated with type 2 diabetes - Li - - Alimentary Pharmacology & Therapeutics - Wiley Online L...

Summary

Background

The role of hepatitis C (HCV) eradication on the long‐term complications of type 2 diabetes mellitus remains incompletely studied.

Aim

We investigated whether antiviral treatment impacted risk of acute coronary syndrome, end‐stage renal disease, ischaemic stroke, and retinopathy among diabetic patients from the four US health systems comprising the Chronic Hepatitis Cohort Study (CHeCS).

Methods

We included CHeCS HCV patients with diagnosis codes for type 2 diabetes who were on antidiabetic medications. Patients were followed until an outcome of interest, death, or last health system encounter. The effect of treatment on outcomes was estimated using the competing risk analysis (Fine‐Gray subdistribution hazard ratio [sHR]), with death as a competing event.

Results

Among 1395 HCV‐infected patients with type 2 diabetes, 723 (52%) were treated with either interferon‐based or direct‐acting antivirals (DAAs); 539 (75% of treated) achieved sustained virological response (SVR). After propensity score adjustment to address treatment selection bias, patients with SVR demonstrated significantly decreased risk of acute coronary syndrome (sHR = 0.36; P < 0.001), end‐stage renal disease (sHR = 0.46; P < 0.001), stroke (sHR = 0.34; P < 0.001), and retinopathy (sHR = 0.24; P < 0.001) compared to untreated patients. Results were consistent in subgroup analyses of DAA‐treated patients and interferon‐treated patients, an analysis of cirrhotic patients, as well as in sensitivity analyses considering cause‐specific hazards, exclusion of patients with on‐treatment retinopathy, and treatment status as a time‐varying covariate.

Conclusion

Successful HCV treatment among patients with type 2 diabetes significantly reduces incidence of acute coronary syndrome, end‐stage renal disease, ischaemic stroke, and retinopathy, regardless of cirrhosis. Our findings support the importance of HCV antiviral therapy among patients with type 2 diabetes to reduce the risk of these extrahepatic outcomes.

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Detection of Hepatitis C virus in an exhumed body identifies the origin of a nosocomial transmission which caused multiple fatal diseases

Detection of Hepatitis C virus in an exhumed body identifies the origin of a nosocomial transmission which caused multiple fatal diseases | Hepatitis C New Drugs Review | Scoop.it
Medico-legal conflicts arise when it is difficult to prove the cause of nosocomial
infections.
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The HCV care continuum: linkage to HCV care and treatment among patients at an urban health network, Philadelphia, PA - Coyle - - Hepatology - Wiley Online Library

The HCV care continuum: linkage to HCV care and treatment among patients at an urban health network, Philadelphia, PA - Coyle - - Hepatology - Wiley Online Library | Hepatitis C New Drugs Review | Scoop.it
Background/Aims Improving care and treatment for persons infected with hepatitis C virus (HCV) can reduce HCV‐related morbidity and mortality. Our primary objective was to examine the HCV care continuum among patients receiving care at five Federally Qualified Health Centers (FQHCs) in Philadelphia, PA where a testing and linkage to care program had been established. Methods Among the five FQHCs, one served a homeless population, two served public housing residents, one served a majority Hispanic population, and the last, a “test and treat” site, also provided HCV treatment to patients. We analyzed data from electronic health records of patients tested for HCV antibody from 2012‐2016 and calculated the percentage of patients across nine steps of the HCV care continuum ranging from diagnosis to cure. We further explored factors associated with successful patient navigation through two steps of the continuum using multivariable logistic regression. Results Of 885 chronically infected patients, 92.2% received their RNA positive result, 82.7% were referred to an HCV provider, 69.4% were medically evaluated by the provider, 55.3% underwent liver disease staging, 15.0% initiated treatment, 12.0% completed treatment, 8.7% were assessed for sustained virologic response (SVR), and 8.0% achieved SVR. Regression results revealed that test and treat site patients were significantly more likely to be medically evaluated (aOR=2.76; 95% CI=1.82, 4.17) and undergo liver disease staging (aOR=1.92, 95% CI=1.02, 2.86) than patients at the other FQHCs combined. Conclusions In this U.S. urban setting, over two‐thirds of HCV‐infected patients were linked to care. Although treatment uptake was low overall, it was highest at the test and treat site. Scaling up treatment services in HCV testing settings will be vital to improve the HCV care continuum. This article is protected by copyright. All rights reserved.
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Hepatitis C elimination: challenges with under-diagnosis and under-treatment - F1000Research

Hepatitis C elimination: challenges with under-diagnosis and under-treatment - F1000Research | Hepatitis C New Drugs Review | Scoop.it
Hepatitis C infection has affected 189 million people globally and more than 4 million in the US. Owing to remarkable advances in the therapeutic sphere, essentially all infected patients can be expected to achieve cure.
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Simtuzumab for Primary Sclerosing Cholangitis: Phase 2 Study Results With Insights on the Natural History of the Disease - Muir - - Hepatology - Wiley Online Library

Simtuzumab for Primary Sclerosing Cholangitis: Phase 2 Study Results With Insights on the Natural History of the Disease - Muir - - Hepatology - Wiley Online Library | Hepatitis C New Drugs Review | Scoop.it
Lysyl oxidase like‐2 (LOXL2) plays a central role in fibrogenesis and is elevated in the serum and liver of patients with primary sclerosing cholangitis (PSC). We evaluated the safety and efficacy of simtuzumab, a monoclonal antibody directed against LOXL2, in patients with PSC. Patients with compensated liver disease caused by PSC were randomized 1:1:1 to receive weekly subcutaneous injections of simtuzumab 75 mg, simtuzumab 125 mg, or placebo for 96 weeks. The primary efficacy endpoint was mean change in hepatic collagen content assessed by morphometry between baseline and week 96. Additional endpoints included change in Ishak fibrosis stage and the frequency of PSC‐related clinical events. Overall, 234 patients were randomized and started treatment. At week 96, the mean change from baseline in hepatic collagen content was –0.5% for patients receiving simtuzumab 75 mg (P = 0.73 versus placebo), +0.5% for patients receiving simtuzumab 125 mg (P = 0.33 versus placebo), and 0.0 for patients receiving placebo. Compared with placebo, neither dose of simtuzumab led to significant reductions in Ishak fibrosis stage, progression to cirrhosis, or frequency of clinical events. Overall, 80 (34%) patients had fibrosis progression and 47 (20%) experienced PSC‐related clinical events. In a multivariate model of baseline factors, PSC‐related clinical events were more frequent in patients with advanced fibrosis (hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.02‐4.06; P = 0.045), higher alkaline phosphatase (HR per 10 U/L, 1.01; 95% CI, 1.00‐1.02; P = 0.015), and higher enhanced liver fibrosis score (HR per unit, 1.26; 95% CI, 0.98‐1.61; P = 0.073). Overall, rates of adverse events and laboratory abnormalities were similar between groups. Conclusion: Treatment with the LOXL2 inhibitor simtuzumab for 96 weeks did not provide clinical benefit in patients with PSC.
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Population Pharmacokinetic Analysis of Daclatasvir, Asunaprevir, and Beclabuvir Combination in HCV‐Infected Subjects

Population Pharmacokinetic Analysis of Daclatasvir, Asunaprevir, and Beclabuvir Combination in HCV‐Infected Subjects | Hepatitis C New Drugs Review | Scoop.it

Abstract

A fixed‐dose combination of daclatasvir (pangenotypic NS5A inhibitor), asunaprevir (NS3/4A protease inhibitor), and beclabuvir (nonnucleoside NS5B inhibitor) was approved for hepatitis C virus treatment in Japan. The objectives of the analyses were to develop the daclatasvir, asunaprevir, and beclabuvir population pharmacokinetic models for the combination regimen. First, an original population pharmacokinetic model was developed using the data in non‐Japanese hepatitis C virus–infected subjects. The model was subsequently updated after a phase 3 study in Japanese hepatitis C virus–infected subjects was available. A total of 11,382, 11,300, and 10,728 pharmacokinetic records from 1,228 subjects were included for daclatasvir, asunaprevir, and beclabuvir in the updated model, respectively. Daclatasvir and beclabuvir pharmacokinetics (PK) were described by a 1‐compartment model with linear elimination and asunaprevir PK was described by 2‐compartment model with linear elimination. Cirrhosis, baseline, and time‐varying ALT were significant covariates on asunaprevir apparent oral clearance. Asian subjects had greater asunaprevir and beclabuvir exposures than white subjects. The effects of all covariates on daclatasvir PK were modest and not considered clinically significant. With the exception of race on asunaprevir and beclabuvir PK, no other parameters for daclatasvir, asunaprevir and beclabuvir population PK models were meaningfully impacted during the refinement with Japanese subjects.

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cobas® HCV Test

cobas® HCV Test | Hepatitis C New Drugs Review | Scoop.it
US-IVD cobas® HCV is an in vitro nucleic acid amplification test for both the detection and quantitation of hepatitis C virus RNA, in human EDTA plasma or serum, of HCV antibody positive or HCV-infected individuals. Specimens containing HCV genotypes 1 to 6 are validated for detection and quantitation in the assay. cobas® HCV is intended for use as an aid in the diagnosis of HCV infection in the following populations: individuals with antibody evidence of HCV with evidence of liver disease, individuals suspected to be actively infected with HCV antibody evidence, and individuals at risk for HCV infection with antibodies to HCV. Detection of HCV RNA indicates that the virus is replicating and therefore is evidence of active infection. cobas® HCV is intended for use as an aid in the management of HCV-infected patients undergoing anti-viral therapy. The assay can be used to measure HCV RNA levels at baseline, during treatment, at the end of treatment, and at the end of follow up of treatment to determine sustained or non-sustained viral response. The results must be interpreted within the context of all relevant clinical and laboratory findings. cobas® HCV has not been approved for use as a screening test for the presence of HCV in blood or blood products. Assay performance characteristics have been established for individuals treated with certain direct-acting antiviral agents (DAA) regimens. No information is available on the assay’s predictive value when other DAA combination therapies are used.
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The long noncoding RNA LncHDAC2 drives the self-renewal of liver cancer stem cells via activation of Hedgehog Signaling

The long noncoding RNA LncHDAC2 drives the self-renewal of liver cancer stem cells via activation of Hedgehog Signaling | Hepatitis C New Drugs Review | Scoop.it
Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is one
of the leading lethal malignancies globally. The highest incidence of HCC is in East
and South-East Asia and Northern and Western Africa[1].
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Hepatitis C Genotype 3 Treated with Shortened Glecapravir/Pibrentasvir

Hepatitis C Genotype 3 Treated with Shortened Glecapravir/Pibrentasvir | Hepatitis C New Drugs Review | Scoop.it
Analysis of data from phase 2 and 3 trials supports an HCV genotype 3 indication for glecaprevir/pibrentasvir, and confirms its efficacy over 8 weeks.
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Host–pathogen interactions in chronic HBV infection and transplantation of HCV-positive organs

Host–pathogen interactions in chronic HBV infection and transplantation of HCV-positive organs | Hepatitis C New Drugs Review | Scoop.it
HBV and HCV infections continue to be major global health problems, causing over 1 million deaths annually. Key studies this year investigated the innate and adaptive immune responses in different clinical scenarios in HBV infection, whereas others evaluated the merits of transplanting...
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Genetic and structural insights into broad neutralization of hepatitis C virus by human VH1-69 antibodies

Genetic and structural insights into broad neutralization of hepatitis C virus by human VH1-69 antibodies | Hepatitis C New Drugs Review | Scoop.it
An effective vaccine to the antigenically diverse hepatitis C virus (HCV) must target conserved immune epitopes. Here, we investigate cross-neutralization of HCV genotypes by broadly neutralizing antibodies (bNAbs) encoded by the relatively abundant human gene family V H 1-69 . We have deciphered the molecular requirements for cross-neutralization by this unique class of human antibodies from crystal structures of HCV E2 in complex with bNAbs. An unusually high binding affinity is found for germ line–reverted versions of VH1-69 precursor antibodies, and neutralization breadth is acquired during affinity maturation. Deep sequencing analysis of an HCV-immune B cell repertoire further demonstrates the importance of the V H 1-69 gene family in the generation of HCV bNAbs. This study therefore provides critical insights into immune recognition of HCV with important implications for rational vaccine design.
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Hepatitis C Virus Protocols | SpringerLink

Hepatitis C Virus Protocols | SpringerLink | Hepatitis C New Drugs Review | Scoop.it
This volume details the most updated concepts and experimental protocols developed by leading researchers in the field.Chapters guide readers through methods on bioinformatics tools, hepatitis c viru...
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