Oral immunization with HCV-NS3-transformed Salmonella: induction of HCV-specific CTL in a transgenic mouse model.

Abstract Background & Aims: The ability to induce cytotoxic T cells is considered an important feature of a candidate hepatitis C virus (HCV) vaccine. We used an oral immunization strategy with attenuated HCV-NS3–transformed Salmonella typhimurium to deliver DNA directly to the gut-associated lymphoid tissue. Methods: HLA-A2.1 transgenic mice were immunized once with transformed attenuated Salmonella . HCV-specific CD8 + T cells were analyzed in vitro as well as in vivo by challenge of mice with recombinant HCV-NS3 vaccinia virus. Results: Salmonella (10 8 colony-forming units; 20 μg plasmid DNA) induced cytotoxic and IFN-γ–producing CD8 + T cells specific for the immunodominant epitope NS3…

Clinical management of drug-drug interactions in HCV therapy: Challenges and solutions.

Contains fulltext : 118153.pdf (Publisher’s version ) (Open Access) Hepatitis C virus (HCV) infected patients often take multiple co-medications to treat adverse events related to HCV therapy, or to manage other co-morbidities. Drug-drug interactions associated with this polypharmacy are relatively new to the field of HCV pharmacotherapy. With the advent of the direct-acting antivirals telaprevir and boceprevir, which are both substrates and inhibitors of the cytochrome P450 (CYP) 3A iso-enzyme, knowledge and awareness of drug-drug interactions have become a cornerstone in the evaluation of patients starting and continuing HCV combination therapy. In our opinion, an overview of conducted dr…

DHCR_OST-Cannabis_Alcohol_supplementary_2018-10-30_xyz151015746ed84_3-converted – Supplemental material for Alcohol and Cannabis Consumption Does Not Diminish Cure Rates in a Real-World Cohort of Chronic Hepatitis C Virus Infected Patients on Opioid Substitution Therapy—Data From the German Hepatitis C-Registry (DHC-R)

Supplemental material, DHCR_OST-Cannabis_Alcohol_supplementary_2018-10-30_xyz151015746ed84_3-converted for Alcohol and Cannabis Consumption Does Not Diminish Cure Rates in a Real-World Cohort of Chronic Hepatitis C Virus Infected Patients on Opioid Substitution Therapy—Data From the German Hepatitis C-Registry (DHC-R) by Stefan Christensen, Peter Buggisch, Stefan Mauss, Klaus HW Böker, Tobias Müller, Hartwig Klinker, Tim Zimmermann, Yvonne Serfert, Bernd Weber, Jens Reimer and Heiner Wedemeyer in Substance Abuse: Research and Treatment

Clinical significance of detectable and quantifiable HCV RNA at the end of treatment with ledipasvir/sofosbuvir in GT1 patients

Background & aims AASLD/IDSA treatment guidelines for hepatitis C virus (HCV) infection state that testing for quantitative HCV RNA can be considered at the end of antiviral treatment (EOT) with interferon-free regimens. However, it remains unclear how to respond to a detectable or even quantifiable HCV RNA result. The aim of this study was to analyse the frequency and predictive value of detectable and quantifiable HCV RNA results at the EOT in patients with HCV genotype 1 infection treated with ledipasvir (LDV) and sofosbuvir (SOF) ± ribavirin (RBV) in a large real-world cohort. Methods A retrospective analysis of the DHC-R (Deutsches Hepatitis C-Register, German Hepatitis C-Registry) coh…

Hepatitis E virus-induced primary cutaneous CD30(+) T cell lymphoproliferative disorder.

International audience; BACKGROUND & AIM:Several types of unexplained extra-hepatic manifestations, including haematological disorders, have been reported in the context of hepatitis E virus (HEV) infection. However, the underlying mechanism(s) of these manifestations are unknown. We provide evidence that HEV has an extra-hepatic endothelial tropism that can engage cutaneous T cells towards clonality.METHODS:A patient with a CD30(+) cutaneous T cell lymphoproliferative disorder (T-LPD) and biopsy-proven chronic HEV infection received three rounds of oral ribavirin treatment, administered either without or with interferon, and eventually achieved a sustained virologic response (SVR). Patholo…

S3-Leitlinie „Prophylaxe, Diagnostik und Therapie der Hepatitis-C-Virus (HCV) -Infektion“ : AWMF-Register-Nr.: 021/012

The Fatty Liver Assessment in Germany (FLAG) cohort study identifies large heterogeneity in NAFLD care

Background & Aims NAFLD is a growing health concern. The aim of the Fatty Liver Assessment in Germany (FLAG) study was to assess disease burden and provide data on the standard of care from secondary care. Methods The FLAG study is an observational real-world study in patients with NAFLD enrolled at 13 centres across Germany. Severity of disease was assessed by non-invasive surrogate scores and data recorded at baseline and 12 months. Results In this study, 507 patients (mean age 53 years; 47% women) were enrolled. According to fibrosis-4 index, 64%, 26%, and 10% of the patients had no significant fibrosis, indeterminate stage, and advanced fibrosis, respectively. Patients with advanced fib…

Global Real-World Evidence of Sofosbuvir/Velpatasvir as a Highly Effective Treatment and Elimination Tool in People with Hepatitis C Infection Experiencing Mental Health Disorders.

HCV elimination; Mental health disorders; Sofosbuvir/velpatasvir Eliminación del VHC; Trastornos de salud mental; Sofosbuvir/velpatasvir Eliminació del VHC; Trastorns de salut mental; Sofosbuvir/velpatasvir Hepatitis C virus (HCV) is prevalent in people with mental health disorders, a priority population to diagnose and cure in order to achieve HCV elimination. This integrated analysis pooled data from 20 cohorts in seven countries to evaluate the real-world effectiveness of the pangenotypic direct-acting antiviral (DAA) sofosbuvir/velpatasvir (SOF/VEL) in people with mental health disorders. HCV-infected patients diagnosed with mental health disorders who were treated with SOF/VEL for 12 w…

Alcohol and Cannabis Consumption Does Not Diminish Cure Rates in a Real-World Cohort of Chronic Hepatitis C Virus Infected Patients on Opioid Substitution Therapy-Data From the German Hepatitis C-Registry (DHC-R).

Background: The importance of alcohol and cannabis consumption for the effectiveness of treatment of chronic hepatitis C virus (HCV) infection with direct acting antivirals (DAAs) in people on opioid substitution therapy (OST) has not been investigated in detail. Methods: We investigated sustained virological response (SVR) rates and proportion of lost to follow-up (LTFU) between OST (n = 739) and non-OST patients (n = 7008) in the German Hepatitis C-Registry (Deutsches Hepatitis C-Register, DHC-R), which is a national multicenter prospective non-interventional real-world registry. Non-OST patients comprised patients with former/current drug use (non-OST/DU; n = 1500) and patients never con…

Hepatitis C: The beginning of the end-key elements for successful European and national strategies to eliminate HCV in Europe

Abstract: Hepatitis C virus (HCV) infection is a major public health problem in the European Union (EU). An estimated 5.6 million Europeans are chronically infected with a wide range of variation in prevalence across European Union countries. Although HCV continues to spread as a largely silent pandemic, its elimination is made possible through the availability of the new antiviral drugs and the implementation of prevention practices. On 17 February 2016, the Hepatitis B & C Public Policy Association held the first EU HCV Policy Summit in Brussels. This summit was an historic event as it was the first high-level conference focusing on the elimination of HCV at the European Union level. The …

Global prevalence and genotype distribution of hepatitis C virus infection in 2015:a modelling study

WOS: 000426979400014

Performance of two HCV RNA assays during protease inhibitor-based triple therapy in patients with advanced liver fibrosis and cirrhosis.

Introduction: On-treatment HCV RNA measurements are crucial for the prediction of a sustained virological response (SVR) and to determine treatment futility during protease inhibitor-based triple therapies. In patients with advanced liver disease an accurate risk/benefit calculation based on reliable HCV RNA results can reduce the number of adverse events. However, the different available HCV RNA assays vary in their diagnostic performance. Aim: To investigate the clinical relevance of concordant and discordant results of two HCV RNA assays during triple therapy with boceprevir and telaprevir in patients with advanced liver fibrosis/cirrhosis. Methods: We collected on-treatment samples of 1…

Treatment Extension of Pegylated Interferon Alpha and Ribavirin Does Not Improve SVR in Patients with Genotypes 2/3 without Rapid Virological Response (OPTEX Trial): A Prospective, Randomized, Two-Arm, Multicentre Phase IV Clinical Trial

UNLABELLED Although sofosbuvir has been approved for patients with genotypes 2/3 (G2/3), many parts of the world still consider pegylated Interferon alpha (P) and ribavirin (R) as standard of care for G2/3. Patients with rapid virological response (RVR) show response rates >80%. However, SVR (sustained virological response) in non-RVR patients is not satisfactory. Longer treatment duration may be required but evidence from prospective trials are lacking. A total of 1006 chronic HCV genotype 2/3 patients treated with P/R were recruited into a German HepNet multicenter screening registry. Of those, only 226 patients were still HCV RNA positive at week 4 (non-RVR). Non-RVR patients with ongoin…

IMPACT OF DIRECT-ACTING ANTIVIRAL THERAPY ON THE NEED FOR LIVER TRANSPLANTATION RELATED TO HEPATITIS C IN GERMANY

Resistance-associated substitutions in patients with chronic hepatitis C virus genotype 4 infection

Data on the prevalence of resistance-associated substitutions (RASs) and their implications for treatment with direct-acting antivirals (DAAs) are sparse in European patients with HCV genotype 4. This study investigated RASs before and after DAA failure in different genotype 4 subtypes and evaluated retreatment efficacies. Samples of 195 genotype 4-infected patients were collected in the European Resistance Database and investigated for NS3, NS5A and NS5B RASs. Retreatment efficacies in DAA failure patients were analysed retrospectively. After NS5A inhibitor (NS5Ai) failure, subtype 4r was frequent (30%) compared to DAA-naive patients (5%) and the number of NS5A RASs was significantly highe…

Effects of Ribavirin Dose Reduction vs Erythropoietin for Boceprevir-Related Anemia in Patients With Chronic Hepatitis C Virus Genotype 1 Infection—A Randomized Trial

International audience; Background & AimsTreatment of hepatitis C virus (HCV) infection with boceprevir, peginterferon, and ribavirin can lead to anemia, which has been managed by reducing ribavirin dose and/or erythropoietin therapy. We assessed the effects of these anemia management strategies on rates of sustained virologic response (SVR) and safety.MethodsPatients (n = 687) received 4 weeks of peginterferon and ribavirin followed by 24 or 44 weeks of boceprevir (800 mg, 3 times each day) plus peginterferon and ribavirin. Patients who became anemic (levels of hemoglobin approximately ≤10 g/dL) during the study treatment period (n = 500) were assigned to groups that were managed by ribavi…

Hepatitis C virus: Current steps toward elimination in Germany and barriers to reaching the 2030 goal

Abstract Hepatitis C virus (HCV) affects over 70 million people globally, with an estimated 399 000 HCV‐related deaths in 2016. The World Health Organization (WHO) has set a goal to eliminate HCV by 2030. Despite the availability of direct‐acting antivirals—highly effective and well‐tolerated therapies for HCV—many patients infected with HCV in Germany have not initiated treatment, including a majority of those who are aware of their positive diagnosis. Barriers to screening, diagnosis, and treatment are major factors taking many countries off track for HCV elimination by 2030. Identifying country‐specific barriers and challenges, particularly in at‐risk populations such as people who injec…

Direct-acting antiviral treatment of chronic HCV-infected patients on opioid substitution therapy: Still a concern in clinical practice?

BACKGROUND AND AIMS There is limited real-world information on the effectiveness of antiviral treatment of chronic hepatitis C virus (HCV) infection with direct-acting antivirals (DAA) in people on opioid substitution therapy (OST). This study compared sustained virological response (SVR) rates and proportion of lost to follow-up (LTFU) between OST and non-OST patients in the German Hepatitis C-Registry (DHC-R). DESIGN National multi-centre prospective real-world registry (German Hepatitis C-Registry, DHC-R). Non-OST patients comprised patients with former/current drug use (non-OST/DU) and patients never consuming drugs (non-OST/NDU). SETTING A total of 254 medical centres in Germany, inclu…

Real-world effectiveness of ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin in patients with hepatitis C virus genotype 1 or 4 infection: A meta-analysis.

The direct-acting antiviral regimen of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) ± dasabuvir (DSV) ± ribavirin (RBV) demonstrated high rates of sustained viral response at post-treatment week 12 (SVR12) in clinical trials for treatment of hepatitis C virus (HCV) genotypes (GT) 1 and 4. To confirm the effectiveness of this regimen in the real world, we conducted meta-analyses of published literature on 30 April 2016. Freeman-Tukey transformation determined the SVR rate within GTs 1a, 1b, and 4, as well as specific SVR rates by cirrhosis or prior treatment experience status. Rates of virologic relapse, hepatic decompensation, drug discontinuation, and serious adverse events were also …

Safety and immunogenicity of the therapeutic vaccine TG1050 in chronic hepatitis B patients: a phase 1b placebo-controlled trial

Funding: Transgène; International audience; Treatment of chronic hepatitis B (CHB) typically requires life-long administration of drugs. Cohort and pre-clinical studies have established the link between a functional T-cell-mounted immunity and resolution of infection. TG1050 is an adenovirus 5-based vaccine that expresses HBV polymerase and domains of core and surface antigen and has shown immunogenicity and antiviral effects in mice. We performed a phase 1 clinical trial to assess safety and explore immunogenicity and early efficacy of TG1050 in CHB patients. This randomized, double blind, placebo-controlled study included two sequential phases: one single dose cohort (SD, n = 12) and one …

Long-Term Efficacy of Tenofovir Monotherapy for Hepatitis B Virus-Monoinfected Patients After Failure of Nucleoside/Nucleotide Analogues

Tenofovir disoproxil fumarate (TDF) has demonstrated high antiviral efficacy in treatment-naive patients with chronic hepatitis B virus (HBV) infection but experience in nucleoside/nucleotide analogue (NA)-experienced patients is limited. In this retrospective multicenter study we therefore assessed the long-term efficacy of TDF monotherapy in patients with prior failure or resistance to different NA treatments. Criteria for inclusion were HBV DNA levels >4.0 log(10) copies/mL at the start and a minimum, period of TDF therapy for at least 6 months. In all, 131 patients (mean age 42 +/- 12 years, 95 male, 65% hepatitis B e antigen [HBeAg]-positive) were eligible. Pretreatment consisted of…

The case for simplifying and using absolute targets for viral hepatitis elimination goals

The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries’ progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes …

Early monotherapy with pegylated interferon alpha-2b for acute hepatitis C infection: the HEP-NET acute-HCV-II study.

Early treatment of acute hepatitis C with interferon alpha-2b for 24 weeks prevents chronic infection in almost all patients. Because pegylated interferons have replaced conventional interferon in the therapy of chronic hepatitis C, the aim of this study was to analyze the efficacy of an early treatment of acute hepatitis C with peginterferon alpha-2b. Between February 2001 and February 2004, 89 individuals with acute HCV infection were recruited at 53 different centers in Germany. Patients received 1.5 microg/kg peginterferon alpha-2b for 24 weeks; treatment was initiated after a median of 76 days after infection (range 14-150). End-of-treatment response and sustained virological response …