Publications by authors named "Stéphane Chevaliez"

107 Publications

Performance of six rapid diagnostic tests for SARS-CoV-2 antigen detection and implications for practical use.

J Clin Virol 2021 09 25;142:104930. Epub 2021 Jul 25.

Department of Virology, Hôpital Henri Mondor, Créteil, France; INSERM U955, Créteil, France. Electronic address:

Background: Direct detection of SARS-CoV-2 viral proteins in nasopharyngeal swabs using lateral flow immunoassays is a simple, fast and cheap approach to diagnose the infection.

Aims And Methods: The performance of 6 SARS-CoV-2 antigen rapid diagnostic tests has been assessed in 634 hospitalized patients or outpatients including 297 patients found to be positive for SARS-CoV-2 RNA by means of RT-PCR and 337 patients presumed to be SARS-CoV-2 RNA-negative.

Results: The specificity of SARS-CoV-2 RDTs was generally high (398.5%). One assay had a lower specificity of 93.2%. The overall sensitivity of the 6 RDTs was variable, from 32.3% to 61.7%. Sensitivity correlated with the delay of sampling after the onset of symptoms and the viral load estimated by the Ct value in RT-PCR. Four out of 6 RDTs tested achieved sensitivities 380% when clinical specimens were collected during the first 3 days following symptom onset or with a Ct value ≤25.

Conclusions: The present study shows that SARS-CoV-2 antigen can be easily and reliably detected by RDTs. These tests are easy and rapid to perform. However, the specificity and sensitivity of COVID-19 antigen RDTs may widely vary across different tests and must therefore be carefully evaluated before releasing these assays for realworld applications.
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http://dx.doi.org/10.1016/j.jcv.2021.104930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310570PMC
September 2021

NON-INVASIVE DIAGNOSIS AND FOLLOW-UP OF CHRONIC INFECTION WITH HEPATITIS B VIRUS.

Clin Res Hepatol Gastroenterol 2021 Jul 28:101773. Epub 2021 Jul 28.

Service d'hépato-gastroentérologie, Hôpital Saint Joseph & INSERM UMR 1252 IRD SESSTIM Aix Marseille Université, Marseille.

Diagnosis of chronic hepatitis B virus (HBV) infection, initial staging of infection and monitoring of treated and untreated patients are mainly based on clinical, biological and imaging criteria allowing a complete non-invasive management for the majority of patients. Along to the conventional virological tools, rapid diagnostic tests and blotting paper tests for HBV DNA are validated alternatives. After diagnosis, the initial work-up should include HIV, HCV and HDV serologies, HBeAg status, and HBsAg and HBV DNA quantification. Assessment of severity (inflammation and fibrosis) is based on ALT serum levels and non-invasive evaluation of liver fibrosis by elastography or blood tests, which must be interpreted cautiously using specific cut-offs and taking into account ALT levels. Taken together, these parameters allow disease classification and treatment decision. Decision of hepatocellular carcinoma screening by ultra-sound every six months may be difficult in non-cirrhotic patients and the use of risk-scores such as PAGE-B is encouraged. Chronic HBV infection often has a dynamic and often unpredictable profile and regular monitoring is mandatory. In untreated patients, regular (3-12 months) follow-up should include ALT and HBV DNA serum levels. Periodical HBsAg quantification and non-invasive evaluation of liver fibrosis may refine disease outcome and prognosis. In treated patients, checking efficacy is mainly based on HBV DNA negativity. In patients with advanced fibrosis, evolution of liver stiffness can be useful for portal hypertension evaluation, but its improvement should not be considered to stop hepatocellular carcinoma screening. Finally, new parameters (HBV RNA, HBcrAg) are promising but their use is still restricted for research.
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http://dx.doi.org/10.1016/j.clinre.2021.101773DOI Listing
July 2021

NON-INVASIVE DIAGNOSIS AND FOLLOW-UP OF CHRONIC INFECTION WITH HEPATITIS C VIRUS.

Clin Res Hepatol Gastroenterol 2021 Jul 28:101771. Epub 2021 Jul 28.

Service d'hépato-gastroentérologie, Hôpital Haut-Lévêque, CHU Bordeaux, pessac & INSERM U1053, Université de Bordeaux, Bordeaux.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. Clinical care for patients with HCV-related liver disease has advanced considerably with developments in screening, diagnostic procedures to evaluate liver fibrosis and improvements in therapy with pangenotypic direct antivirals and prevention. These AFEF guidelines on the non-invasive diagnosis and follow up of chronic infection with HCV describe the optimal management of HCV positive patients with non-invasive methods in screening, in assessing viral disease and liver fibrosis and the follow-up of these patients according to the value of FibroScan®, Fibrotest® or Fibrometer®. Hepatocellular carcinoma screening must continue in patients with liver stiffness by FibroScan® ≥10 kPa or Fibrotest® >0.58 or Fibrometer® >0.78 prior to treatment initiation. After reaching sustained virologic response, patients with a measurement of liver stiffness by FibroScan®<10 kPa or Fibrotest®≤0.58 or Fibrometer®≤0.78 before treatment initiation and without liver comorbidity (alcohol consumption, metabolic syndrome, HBV co-infection etc.) no longer require specific monitoring. The role of liver biopsy is discussed in some rare situations.
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http://dx.doi.org/10.1016/j.clinre.2021.101771DOI Listing
July 2021

Performance of rapid diagnostic tests for HCV infection in serum or plasma.

Future Microbiol 2021 Jul 6;16:713-719. Epub 2021 Jul 6.

Department of Virology, Centre Pasteur du Cameroun, Yaounde, Cameroon.

HCV diagnosis will become the bottleneck in eliminating hepatitis C. Simple, accurate and cost-effective testing strategies are urgently needed to improve hepatitis C screening and diagnosis. Performance of seven rapid diagnostic tests (RDT) have been assessed in a large series (n = 498) of serum or plasma specimens collected in France and in Cameroon. Specificity varied from 96.1 to 100%. The clinical sensitivity, compared with immunoassays as the reference, was high for all seven RDT (97.2-100%). The Multisure HCV antibody assay and OraQuick HCV rapid antibody test reached sensitivity ≥99%. A number of RDT may be suitable for WHO prequalification and may be implemented in the framework of large-scale low-cost treatment programs to achieve the WHO viral hepatitis objectives by 2030.
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http://dx.doi.org/10.2217/fmb-2020-0295DOI Listing
July 2021

Dried blood spot sampling for hepatitis C virus infection: A new tool to simplify testing algorithms.

J Clin Virol 2021 Aug 3;141:104876. Epub 2021 Jun 3.

Department of Virology, Hôpital Henri Mondor, Créteil, France; INSERM U955, Créteil, France. Electronic address:

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http://dx.doi.org/10.1016/j.jcv.2021.104876DOI Listing
August 2021

Diagnosis and monitoring of hepatitis C virus infection using the cobas® HCV test for use on the cobas® 4800 system.

J Clin Virol 2021 Aug 29;141:104873. Epub 2021 May 29.

National Reference Center for Viral Hepatitis B, C and Delta, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France; INSERM U955, Créteil, France. Electronic address:

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http://dx.doi.org/10.1016/j.jcv.2021.104873DOI Listing
August 2021

Diagnosis and Monitoring of Hepatitis B Virus Infection Using the Cobas HBV Test for Use on the Cobas 4800 System.

Microorganisms 2021 Mar 11;9(3). Epub 2021 Mar 11.

National Reference Center for Viral Hepatitis B, C and delta, Department of Virology, hôpital Henri Mondor, Université Paris-Est, 94000 Créteil, France.

(1) Background: Sensitive and accurate nucleic acid amplification technologies are now recommended for hepatitis B virus (HBV) DNA detection and quantification in clinical practice to diagnose and monitor hepatitis B infection. The aim of this study was to assess the analytical and clinical performance of the cobas HBV Test on the cobas 4800 System. (2) Methods: Standard panel and clinical specimens were tested in parallel with three different real-time commercial PCR assays including the cobas HBV Test, the Cobas AmpliPrep/Cobas TaqMan HBV Test v2.0 and Alinity™ HBV assay. (3) Results: The specificity of the cobas HBV Test was 97.9%. The limit of detection was estimated to be 2.1 IU/mL. Intra-assay and interassay coefficients of variation varied from 0.14% to 1.92% and 2.16% to 12.02%, respectively. HBV DNA levels in patients infected with different HBV genotypes strongly correlated with those measured by the two other commercial comparators assays. (4) Conclusions: The cobas HBV Test can be confidently used to detect and accurately quantify HBV DNA in clinical practice as well as in clinical trials with the new anti-HBV drugs currently in development.
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http://dx.doi.org/10.3390/microorganisms9030573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999133PMC
March 2021

Performance of rapid diagnostic tests for hepatitis B surface antigen detection in serum or plasma.

Diagn Microbiol Infect Dis 2021 Jun 17;100(2):115353. Epub 2021 Feb 17.

Department of Virology, Centre Pasteur du Cameroun, Yaounde, Cameroon.

Hepatitis B surface antigen (HBsAg) is a key marker for screening and laboratory diagnosis of HBV infection. Rapid diagnostic tests (RDTs) represent promising alternatives to immunoassay-based methods because they are simple, fast and cheap. These tests, therefore, represent a powerful tool for large-scale screening and diagnosis of HBV infection in the clinical setting. Performance of 6 RDTs have been assessed in a large series of serum or plasma samples (n = 501) collected in France and in Cameroon. Specificity varied from 98.0% to 99.5%, while clinical sensitivity, compared to immunoassays as the reference, was excellent for all six RDTs (98.3%-99.3%). The VIKIA HBsAg and First Response HBsAg Card Test reached sensitivity ≥99%. False-negative results were rare and mostly encompassed inactive HBsAg carriers or patients treated with nucleoside/nucleotide analogues. A number of RDTs may widely use to increase access to testing to all levels of the health care system.
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http://dx.doi.org/10.1016/j.diagmicrobio.2021.115353DOI Listing
June 2021

Multicenter Evaluation of the Cepheid Xpert HBV Viral Load Test.

Diagnostics (Basel) 2021 Feb 12;11(2). Epub 2021 Feb 12.

Laboratory of Virology, Virology Unit, Polyclinic Tor Vergata Foundation, Viale Oxford, 81, 00133 Rome, Italy.

Accurate measurement of the hepatitis B virus (HBV) DNA is important for the management of patients with chronic HBV infection. Here, the performance of the Xpert HBV Viral Load test (Xpert HBV Viral Load) versus the Roche COBAS Ampliprep/COBAS TaqMan system (CAP/CTM HBV) HBV test v2.0 was evaluated. From September 2017 to December 2017, a total of 876 prospectively collected or archived serum or EDTA plasma specimens from subjects chronically infected with HBV were tested using the Xpert HBV Viral Load and the CAP/CTM HBV v2.0 assays. Of the 876 specimens tested, 560 were within the quantitative range of both assays. The agreement between the two methods was 90.0%. No difference in plasma or serum samples was observed. Deming regression analysis showed a good correlation of the Xpert HBV Viral Load assay with the CAP/CTM HBV v2.0 assay. The Bland-Altman analysis showed a good agreement between the results of the Xpert HBV Viral Load assay and the CAP/CTM HBV assay, with a mean difference (±1.96 standard deviation) of 0.0091 ± 0.3852 Log IU/mL. Comparing the two assays, only nineteen specimens (2.1%) had a difference greater than 1.96 times the standard deviation. The Xpert HBV Viral Load test is suitable for monitoring patients with HBV infection and is useful in diagnostic settings.
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http://dx.doi.org/10.3390/diagnostics11020297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917951PMC
February 2021

Real-world efficacy and safety of direct-acting antiviral drugs in patients with chronic hepatitis C and inherited blood disorders.

Eur J Gastroenterol Hepatol 2020 Nov 17. Epub 2020 Nov 17.

INSERM U955, Team "Viruses, Hepatology, Cancer", Institut Mondor de Recherche Biomédicale (IMRB).

Background: Patients with inherited blood disorders (IBLD) have a high risk of hepatitis C virus (HCV) infection. The aim of this work was to assess the efficacy and safety of HCV direct-acting antiviral (DAA)-based treatment in patients with IBLD and chronic HCV infection.

Methods: Twenty-seven patients (25 with sickle cell disease, 1 with β-thalassemia and 1 with hemoglobin D-Punjab), including 3 with compensated cirrhosis, were included. They were treated with sofosbuvir in combination with ribavirin, daclatasvir, ledipasvir, or velpatasvir or with grazoprevir/elbasvir for 8 or 12 weeks. In the case of treatment failure, in-vitro assessment of resistance-associated substitutions (RASs) and full-length genome sequence analysis by means of deep sequencing were performed.

Results: Treatment was safe and well-tolerated and there were no drug discontinuations due to DAA-related adverse events. Twenty-five out of the 27 patients (93%) achieved sustained virological response 12 weeks post-treatment. One patient discontinued after 18 days due to adverse events unrelated to the antiviral treatment. One patient infected with 'unusual' genotype 2 subtype 2m relapsed. Subtype 2m naturally carries the NS5A L31M RAS. In a genotype 2a subgenomic replicon model, L31M increased daclatasvir effective concentration 50% (EC50) by 97-fold, but velpatasvir EC50 by only 3-fold, without altering the replication capacity. This patient was successfully retreated with sofosbuvir/velpatasvir for 12 weeks.

Conclusion: DAA-based regimens are well tolerated and highly efficacious in patients with chronic hepatitis C and IBLD in the real-world setting. Thus, DAA-based antiviral treatment should be prioritized in this thus far neglected population of HCV-infected patients.
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http://dx.doi.org/10.1097/MEG.0000000000002003DOI Listing
November 2020

French hepatitis C care cascade: substantial impact of direct-acting antivirals, but the road to elimination is still long.

BMC Infect Dis 2020 Oct 15;20(1):759. Epub 2020 Oct 15.

Paris-Saclay University, Versailles Saint-Quentin University, Inserm, CESP, Anti-infective evasion and pharmacoepidemiology, Villejuif, France.

Background: Hepatitis C virus (HCV) elimination by 2030, as targeted by the World Health Organization (WHO), requires that 90% of people with chronic infection be diagnosed and 80% treated. We estimated the cascade of care (CoC) for chronic HCV infection in mainland France in 2011 and 2016, before and after the introduction of direct-acting antivirals (DAAs).

Methods: The numbers of people (1) with chronic HCV infection, (2) aware of their infection, (3) receiving care for HCV and (4) on antiviral treatment, were estimated for 2011 and 2016. Estimates for 1) and 2) were based on modelling studies for 2011 and on a virological sub-study nested in a national cross-sectional survey among the general population for 2016. Estimates for 3) and 4) were made using the National Health Data System.

Results: Between 2011 and 2016, the number of people with chronic HCV infection decreased by 31%, from 192,700 (95% Credibility interval: 150,900-246,100) to 133,500 (95% Confidence interval: 56,900-312,600). The proportion of people aware of their infection rose from 57.7 to 80.6%. The number of people receiving care for HCV increased by 22.5% (representing 25.7% of those infected in 2016), while the number of people on treatment increased by 24.6% (representing 12.1% of those infected in 2016).

Conclusions: This study suggests that DAAs substantially impact CoC. However, access to care and treatment for infected people remained insufficient in 2016. Updating CoC estimates will help to assess the impact of new measures implemented since 2016 as part of the goal to eliminate HCV.
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http://dx.doi.org/10.1186/s12879-020-05478-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559725PMC
October 2020

Fitness-associated substitutions following failure of direct-acting antivirals assessed by deep sequencing of full-length hepatitis C virus genomes.

Aliment Pharmacol Ther 2020 11 4;52(10):1583-1591. Epub 2020 Sep 4.

Department of Virology, National Reference Center for Viral Hepatitis B, C and D, Henri Mondor Hospital, University of Paris-Est, Créteil, France.

Background: In hepatitis C virus (HCV) infection, treatment failure is generally associated with the selection of resistance-associated substitutions (RAS) conferring reduced susceptibility to direct-acting antiviral (DAA) drugs. Resistant variants continue to replicate after the end of treatment with potential for transmission. This may result from the selection of "fitness-associated substitutions".

Aim: To characterise potential "fitness-associated substitutions" in patients infected with genotype 3a failing DAA drugs METHODS: By means of shotgun metagenomics, we sequenced full-length HCV genomes at treatment initiation and at virological relapse in eight patients infected with genotype 3a with cirrhosis failing sofosbuvir and an NS5A inhibitor. The impact of amino acid changes occurring outside of DAA target regions selected in at least two patients were assessed on the in vitro susceptibility to an NS5A inhibitor and replication capacity.

Results: At treatment failure, besides selection of known NS5A RASs, especially Y93H, a large number of amino acid changes was observed outside of DAA target regions. We identified four amino acid positions at which observed changes substantially improved in vitro replication capacity without affecting NS5A inhibitor susceptibility.

Conclusions: This is the first in vivo observation combined with in vitro confirmation of selection of phenotypically characterised "fitness-associated substitutions" together with RASs at the time of sofosbuvir-NS5A inhibitor treatment failure in patients infected with genotype 3a with cirrhosis. Our findings may explain the persistence of resistant HCV variants after treatment in patients who did not achieve sustained virological remission.
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http://dx.doi.org/10.1111/apt.16054DOI Listing
November 2020

Multicenter clinical evaluation of alinity m HCV assay performance.

J Clin Virol 2020 08 3;129:104531. Epub 2020 Jul 3.

West of Scotland Specialist Virology Centre, Glasgow, UK.

Background: Nucleic acid testing is essential for the detection and quantification of HCV RNA in the diagnosis of HCV infection and treatment monitoring. The Alinity m HCV assay was recently developed by Abbott Molecular for rapid detection and quantification of HCV RNA on the fully automated, continuous, random-access Alinity m analyzer.

Objectives: Our study assessed the performance of the new Alinity m HCV assay for detection and quantification of HCV RNA in a large series of patient samples of various genotypes. This international, multicentric study evaluated the linearity, precision, and reproducibility of the Alinity m HCV assay and its performance in comparison to three other HCV assays currently used in clinical practice.

Results: The Alinity m HCV assay demonstrated high linearity (correlation coefficient r = 1.00), precision (coefficients of variation [CV] 6.6-13.5 %) and reproducibility (CV 1.7-4.3 % across three control lots). At a concentration near the lower limit of detection, the Alinity m HCV assay exhibited >98 % detectability. The Alinity m HCV assay showed excellent correlation with comparator HCV assays in serum (n = 406) and plasma (n = 1401) samples (correlation coefficients ≥0.96, bias 0.01 to 0.14 Log IU/mL). More than 95 % of the quantified results with the Alinity m HCV assay were less than mean bias ± 1.96 SD different from those of the comparator assays.

Conclusions: The newly developed Alinity m HCV assay is sensitive, reproducible, and accurately quantifies HCV RNA levels in serum and plasma samples from patients with chronic HCV infection, with no impact of HCV genotype on assay performance.
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http://dx.doi.org/10.1016/j.jcv.2020.104531DOI Listing
August 2020

Multicenter clinical evaluation of alinity m HBV assay performance.

J Clin Virol 2020 08 3;129:104514. Epub 2020 Jul 3.

National Reference Center for Viral Hepatitis B, C, and Delta, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France. Electronic address:

Background: Accurate molecular methods to detect and quantify hepatitis B virus (HBV) DNA are essential to diagnose chronic infections, guide treatment decisions, assess response to treatment, and determine risk of HBV-related complications. New generations of real-time HBV DNA assay platforms provide results in less than 2-3 h, with continuous loading of specimens and true random-access capability.

Objectives: We examined the clinical performance of the new Alinity m HBV assay, run on the fully automated, continuous, random-access Alinity m platform, to accurately detect and quantify HBV DNA in a large series of patient samples infected with different HBV genotypes frequently encountered in clinical practice.

Study Design: This international, multisite study assessed the precision and reproducibility of the Alinity m HBV assay and compared its performance to four HBV assays currently in clinical use.

Results: The Alinity m HBV assay demonstrated linear quantitation of HBV DNA in plasma samples, with high precision (coefficient of variation 4.1 %-8.8 %) and reproducibility. The Alinity m HBV assay showed excellent correlation (correlation coefficients ≥0.947) with comparator HBV assays, with an overall observed bias ranging from -0.07 to 0.17 Log IU/mL. 97 % of quantifiable patient results were <1 Log IU/mL different than the respective comparator assays, with comparable results across HBV genotypes.

Conclusions: The newly developed real-time PCR-based Alinity m HBV assay is sensitive, reproducible, and accurately quantifies HBV DNA levels from HBsAg-positive patients across the full dynamic range of quantification.
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http://dx.doi.org/10.1016/j.jcv.2020.104514DOI Listing
August 2020

A Highly Prevalent Polymorphism in the Core Region Impairs Quantification of Hepatitis B Virus (HBV) by the cobas TaqMan HBV Assay.

J Clin Microbiol 2020 08 24;58(9). Epub 2020 Aug 24.

National Institute of Blood Transfusion, Department of Blood-Borne Agents, National Reference Center for Infectious Risks in Transfusion, Paris, France

The high genetic variability of hepatitis B virus (HBV) can impair DNA quantification. Here, we investigate a major underquantification of HBV by the cobas TaqMan HBV assay (CTM; Roche). In France, between 2005 and 2017, HBV DNA was detected in 3,102 blood donations by use of the CTM (95% limit of detection [LOD], 4.8 IU/ml). HBV strains were sequenced in the S region (LOD, ∼30 IU/ml). Concordant ( = 120) and discordant ( = 45) samples were identified according to the agreement between the plasma viral load (pVL) determined by the CTM and sequencing; all samples were also quantified using the RealTime HBV assay (RTH; Abbott). The viral signature, cloning, and mutagenesis were used to characterize the polymorphism responsible for CTM misquantification. A CTM-RTH discordance (>1 log IU/ml) was found in 14/45 samples that had low pVLs and were successfully genotyped (pVL genoS). PreC/C clones of concordant (C1, C2) and discordant (D1, D2) strains were used to challenge the CTM. Strains D1 and D2 were highly underquantified (42- and 368-fold). In clones, mutating the region corresponding to the CTM reverse primer from a discordant sequence to a concordant sequence restored the levels of quantification to 24% (D1→C1) and 59% (D2→C1) of theoretical levels, while mutating the sequence of a concordant strain to that of a discordant strain led to 78-fold (C1→D1) and 146-fold (C1→D2) decreases in quantification. Moreover, mutating positions 1961 and 1962 was enough to induce a 5-fold underquantification. We conclude that the CTM underestimates pVLs for HBV strains with mutations in the reverse primer target. Specifically, the polymorphism at nucleotides 1961 and 1962 is naturally present in 4.79 and 4.22% of genotype A and D strains, which are highly frequent in Europe, leading to a 5-fold decrease in quantification. Quantification using the new-generation Roche C4800 assay is not affected by this polymorphism.
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http://dx.doi.org/10.1128/JCM.00647-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448625PMC
August 2020

Assessing Molecular Point-of-Care Testing and Dried Blood Spot for Hepatitis C Virus Screening in People Who Inject Drugs.

Open Forum Infect Dis 2020 Jun 26;7(6):ofaa196. Epub 2020 May 26.

Department of Infectious Diseases, Hôpital Henri Mondor, Université Paris-Est, Créteil, France.

Background: Injecting drug use is a major driver of hepatitis C virus (HCV) spread worldwide, and the World Health Organization (WHO) has identified people who inject drugs (PWID) as a key population to target for HCV screening and care. Point-of-care (POC) hepatitis C tests and dried blood spot (DBS) sampling offer benefits for the management of patients with HCV infection by increasing HCV testing and linkage to care in different nonclinical settings. The aims of this prospective study were to evaluate the feasibility and the acceptability of use HCV ribonucleic acid (RNA) POC and fingerstick DBS testing in social-medical risk-reduction centers and to describe the cascade of care among PWID in France.

Methods: Between June 2018 and February 2019, 89 consecutive HCV-seropositive PWID attending 2 drug treatment services and 1 supervised consumption room in inner Paris were invited to participate in further evaluation, undergoing a clinical review with a liver assessment and blood tests including fingerstick capillary whole blood POC HCV RNA testing and fingerstick DBS sampling.

Results: Of the 89 participants enrolled, HCV RNA was detected in 34 (38.6%) participants. Fingerstick whole blood POC RNA testing and HCV RNA detection from DBS sample were feasible and acceptable among PWID with no major difference in terms of HCV RNA detection rate. Overall, 16 participants received pan-genotypic antiviral treatment. The proportion of PWID with sustained virologic response at 12 weeks was 81.2%, with data for 3 patients still pending.

Conclusions: One-step screening strategy based on the detection of HCV RNA would engage people in care for treatment scale-up and HCV elimination.
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http://dx.doi.org/10.1093/ofid/ofaa196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314587PMC
June 2020

Evaluation of the Xpert HBV Viral Load for hepatitis B virus molecular testing.

J Clin Virol 2020 08 1;129:104481. Epub 2020 Jun 1.

National Reference Center for Viral Hepatitis B, C and Delta, Department of Virology, Hôpital Henri Mondor, France; INSERM U955, Créteil, France. Electronic address:

Background: Accurate molecular methods to detect and quantify hepatitis B virus (HBV) DNA are essential to diagnose chronic infections, guide treatment decisions, assess response to treatment, and determine risk of HBV-related complications. New HBV DNA generations of real-time assay platforms are now available with the availability of results in less than 2-3 h and a continuous loading of specimens with true random access.

Objectives: The aim of this prospective study was to evaluate the performance of the new Xpert HBV Viral Load assay to accurately quantify HBV DNA in plasma and in whole blood collected on dried blood spot (DBS).

Methods: Plasma and whole blood from 143 patients chronically infected with HBV were tested in parallel using two commercially real-time PCR assay (Cobas AmpliPrep/Cobas Taqman HBV test, version 2.0, and Xpert HBV Viral Load assay).

Results: HBV DNA levels in whole blood strongly correlated with those measured in plasma. A positive significant correlation between the HBV DNA levels in plasma measured with the new Xpert HBV Viral Load and CAP/CTM HBV v2.0 assays was found.

Conclusions: The newly developed real-time PCR-based assay Xpert HBV Viral Load accurately quantifies HBV DNA in whole blood specimens as well as in plasma samples from patients with chronic HBV infection. Whole blood specimens collected on DBS can be confidently used for replicative HBV infection detection in patients with HBV DNA level above 3 Log using standardized, commercially available methods.
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http://dx.doi.org/10.1016/j.jcv.2020.104481DOI Listing
August 2020

Sofosbuvir-Daclatasvir is suboptimal in patients with genotype 2 chronic hepatitis C infection: real-life experience from the HEPATHER ANRS CO22 cohort.

J Viral Hepat 2020 10 21;27(10):964-973. Epub 2020 May 21.

Hepatology Unit, APHP Cochin, Paris, France.

Sofosbuvir plus daclatasvir with or without ribavirin has demonstrated a high efficacy and an acceptable safety profile in clinical trials of patients infected with genotype 2 hepatitis Cvirus (HCV); however, there are currently no real-world data available for this regimen. To evaluate the real-life safety and efficacy of sofosbuvir/daclatasvir with or without ribavirin in genotype 2 HCV patients in the French cohort ANRS CO22 HEPATHER(NCT01953458). In this ongoing, national, multicentre, prospective, observational study, we observed patients with HCV genotype 2 infection who initiated treatment with sofosbuvir (400 mg/d) plus daclatasvir with or without ribavirin (1-1.2 g/d). Patients were divided into two treatment groups: sofosbuvir/daclatasvir with or without ribavirin (12 weeks/24 weeks). The primary end point was a sustained virological response at week 12 following the end of therapy. Overall, 88% and 91% of patients achieved a sustained virological response following 12 and 24 weeks of treatment with sofosbuvir/daclatasvir with or without ribavirin, respectively. The most common adverse events were asthenia (29%), headache (15%) and fatigue (20%), and ribavirin addition was associated with a higher rate of adverse events and treatment discontinuation. Sofosbuvir/daclatasvir with or without ribavirin was associated with lower rates of sustained virological response in the real-life setting compared with the clinical setting and demonstrated suboptimal efficacy for the treatment of patients with genotype 2 chronic HCV.
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http://dx.doi.org/10.1111/jvh.13321DOI Listing
October 2020

Grazoprevir/elbasvir for the immediate treatment of recently acquired HCV genotype 1 or 4 infection in MSM.

J Antimicrob Chemother 2020 07;75(7):1961-1968

Service de maladies infectieuses et tropicales, Hôpital St Antoine, AP-HP, Paris, France.

Background: In Europe, increases in HCV infection have been observed over the last two decades in MSM, making them a key population for recently acquired HCV. Alternative combinations of direct-acting antiviral agents against early HCV infection need to be assessed.

Patients And Methods: In this pilot trial, MSM with recently acquired genotype 1 or 4 HCV infection were prospectively included and received 8 weeks of oral grazoprevir 100 mg and elbasvir 50 mg in a fixed-dose combination administered once daily. The primary endpoint was sustained virological response evaluated 12 weeks after the end of treatment (EOT) (SVR12). Secondary endpoints were the virological characterization of failures, the quality of life before, during and after treatment and the rate of reinfection.

Results: In a 15 month period, 30 patients were enrolled, all of whom were MSM. Of the 29 patients completing follow-up, 28 (96%, 95% CI = 82%-99%) achieved SVR12. One patient interrupted follow-up (suicide) but had undetectable plasma HCV RNA at EOT. One patient with suboptimal adherence confirmed by plasma drug monitoring relapsed and developed NS3, NS5A and NS5B resistance-associated substitutions (V36M, M28V and S556G). The most common adverse events related to study drug were diarrhoea (n = 4, 13%), insomnia (n = 2, 7%) and fatigue (n = 2, 7%), although no patient discontinued treatment. No HIV RNA breakthrough was reported in the 28 patients with HIV coinfection. At Week 48, reinfection was diagnosed in three patients.

Conclusions: Our data support the use of grazoprevir/elbasvir for immediate treatment against HCV in order to reduce HCV transmission in MSM.
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http://dx.doi.org/10.1093/jac/dkaa091DOI Listing
July 2020

Injecting drug use during sex (known as "slamming") among men who have sex with men: Results from a time-location sampling survey conducted in five cities, France.

Int J Drug Policy 2020 Apr 4;79:102703. Epub 2020 Apr 4.

Cermes 3 (Inserm U988/UMR CNRS 8211/EHESS/Paris Descartes University), 45 rue des Saint Pères, Paris, France; Santé publique france, French national public health agency, Saint-Maurice Cedex, France, 12 rue du Val d'Osne, 94415, Saint-Maurice, France. Electronic address:

Background: In the last decade, European cities saw the development of "slamming," a practice related to chemsex that combines three elements: a sexual context, psychostimulant drug use, and injection practices. Epidemiological data on this practice is still sparse and media attention might have unintentionally distorted the size of this phenomenon. Therefore, we aimed to estimate the prevalence of men practicing slam and to identify factors associated with this practice.

Methods: We used data from the Prevagay 2015 bio-behavioral survey to estimate the prevalence of slamming practices. A time-location sampling was performed among gay-labeled venues in five French cites. Behavioral information was recorded using a self-administered questionnaire. The HIV and HCV serostatus were investigated using ELISA tests on dried blood spots. The factors associated with slamming were assessed using a multiple logistic regression. We applied a weighting mechanism to enhance the generalizability of the estimates.

Results: Among the 2646 men who have sex with men (MSM) included in our study, 3.1% reported slamming at least once during their lifetime (95% confidence interval (CI) = 2.2-4.3) and 1.6% (95% CI = 1-2.3) said they participated in a slamming session in the last 12 months. In the multivariate analysis, both HCV and HIV biological status were strongly associated with practicing "slam" in the last 12 months (OR = 13.37 (95% CI = 3.26-54.81) and 4.73 (95% CI = 1.58-14.44), respectively). Furthermore, a ten-point decrease in mental health scores was linked with the practice with an OR of 1.37 (95% CI = 1.08-1.73), indicating poorer mental health.

Conclusion: Even though slamming seems to involve a relatively small proportion of MSM, the vulnerability of this sub-group is high enough to justify setting up harm reduction measures and specific care. Training health professionals and creating services combining sexual health and drug dependence could be an effective response.
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http://dx.doi.org/10.1016/j.drugpo.2020.102703DOI Listing
April 2020

Hepatitis C virus infection in people who inject drugs in Africa.

Lancet Infect Dis 2020 03;20(3):282-283

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction, Division of Digestive Diseases, Queen Elizabeth the Queen Mother Wing, St Mary's Campus, Imperial College, London W2 1NY, UK. Electronic address:

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http://dx.doi.org/10.1016/S1473-3099(20)30049-9DOI Listing
March 2020

In-field evaluation of Xpert® HCV viral load Fingerstick assay in people who inject drugs in Tanzania.

Liver Int 2020 03 15;40(3):514-521. Epub 2019 Dec 15.

Department of Hepatology, Imperial College London, St Mary's Hospital, London, UK.

Background: Although novel hepatitis C virus (HCV) RNA point-of-care technology has the potential to enhance the diagnosis in resource-limited settings, very little real-world validation of their utility exists. We evaluate the performance of HCV RNA quantification using the Xpert HCV viral load Fingerstick assay (Xpert HCV VL Fingerstick assay) as compared to the World Health Organisation pre-qualified plasma Xpert HCV VL assay among people who inject drugs (PWID) attending an opioid agonist therapy (OAT) clinic in Dar-es-Salaam, Tanzania.

Methods: Between December 2018 and February 2019, consecutive HCV seropositive PWID attending the OAT clinic provided paired venous and Fingerstick samples for HCV RNA quantification. These were processed onsite using the GeneXpert platform located at the Central tuberculosis reference laboratory.

Results: A total of 208 out of 220 anti-HCV-positive participants recruited (94.5%) had a valid Xpert HCV VL result available; 126 (61%; 95% CI 53.8-67.0) had detectable and quantifiable HCV RNA. About 188 (85%) participants had paired plasma and Fingerstick whole blood samples; the sensitivity and specificity for the quantification of HCV RNA levels were 99.1% and 98.7% respectively. There was an excellent correlation (R  = .95) and concordance (mean difference 0.13 IU/mL, (95% CI -0.9 to 0.16 IU/mL) in HCV RNA levels between plasma samples and Fingerstick samples.

Conclusion: This study found excellent performance of the Xpert HCV VL Fingerstick assay for HCV RNA detection and quantification in an African-field setting. Its clinical utility represents an important watershed in overcoming existing challenges to HCV diagnosis, which should play a crucial role in HCV elimination in Africa.
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http://dx.doi.org/10.1111/liv.14315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079170PMC
March 2020

HCV and HBV prevalence based on home blood self-sampling and screening history in the general population in 2016: contribution to the new French screening strategy.

BMC Infect Dis 2019 Oct 28;19(1):896. Epub 2019 Oct 28.

Santé publique France, the national public health agency, HIV, Hepatitis B/C and STI Unit, Saint-Maurice, France.

Background: The advent of effective direct-acting antivirals (DAAs), has prompted an assessment of the French Hepatitis C virus (HCV) screening strategy, which historically targeted high-risk groups. One of the options put forward is the implementation of combined (i.e., simultaneous) HCV, Hepatitis B virus (HBV) and HIV screening for all adults at least once during their lifetime ("universal combined screening"). However, recent national survey-based data are lacking to guide decision-making regarding which new strategy to implement. Accordingly, we aimed to provide updated data for both chronic hepatitis C (CHC) and B (CHB) prevalence and for HCV and HBV screening history, using data from the BaroTest and 2016 Health Barometer (2016-HB) studies, respectively.

Methods: 2016-HB was a national cross-sectional phone based health survey conducted in 2016 among 20,032 randomly selected individuals from the general population in mainland France. BaroTest was a virological sub-study nested in 2016-HB. Data collected for BaroTest were based on home blood self-sampling on dried blood spots (DBS).

Results: From 6945 analyzed DBS, chronic hepatitis C (CHC) and B (CHB) prevalence was estimated at 0.30% (95% Confidence Interval (CI): 0.13-0.70) and 0.30% (95% CI: 0.13-0.70), respectively. The proportion of individuals aware of their status was estimated at 80.6% (95% CI: 44.2-95.6) for CHC and 17.5% (95% CI: 4.9-46.4) for CHB. Universal combined screening would involve testing between 32.6 and 85.3% of 15-75 year olds according to whether we consider only individuals not previously tested for any of the three viruses, or also those already tested for one or two of the viruses.

Conclusions: Our data are essential to guide decision-making regarding which new HCV screening recommendation to implement in France. They also highlight that efforts are still needed to achieve the WHO's targets for eliminating these diseases. Home blood self-sampling may prove to be a useful tool for screening and epidemiological studies.
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http://dx.doi.org/10.1186/s12879-019-4493-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819439PMC
October 2019

The new Xpert HCV viral load real-time PCR assay accurately quantifies hepatitis C virus RNA in serum and whole-blood specimens.

J Clin Virol 2019 08 22;117:80-84. Epub 2019 Jun 22.

National Reference Center for Viral Hepatitis B, C, and Delta, Department of Virology, hôpital Henri Mondor, France; INSERM U955, Créteil, France. Electronic address:

Background: Sensitive and accurate hepatitis C virus (HCV) RNA detection and quantification are essential to diagnose and monitor the virological response to antiviral treatment and the emergence of resistance.

Objective And Study Design: The aim of this study was to assess the ability of the new Xpert HCV Viral Load assay to accurately detect and quantify HCV RNA in serum and in whole blood collected on dried blood spot (DBS). Serum and whole blood from a large series of patients chronically infected with different HCV genotypes were tested in parallel for HCV RNA detection and quantification.

Results: A significant relationship between HCV RNA levels measured with the Xpert HCV Viral Load assay and the two commercial real-time PCR comparators (Abbott RealTime HCV test and Cobas AmpliPrep/Cobas Taqman HCV 2.0 test) was found in serum as well as in whole blood specimens.

Conclusions: The Xpert HCV Viral Load assay accurately quantifies HCV RNA regardless of the HCV genotype and can thus confidently be used to detect active HCV infection in serum and in whole blood specimens.
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http://dx.doi.org/10.1016/j.jcv.2019.06.007DOI Listing
August 2019

Performance assessment of a fully automated deep sequencing platform for HCV resistance testing.

Antivir Ther 2019 ;24(6):417-423

Department of Virology, National Reference Center for Viral Hepatitis B, C and Delta, Hôpital Henri Mondor, Université Paris-Est, Créteil, France.

Background: International liver society guidelines recommended to perform HCV resistance testing at baseline of first-line therapy with certain combination regimens or prior to retreatment in patients previously exposed to a direct-acting antiviral (DAA) containing regimen. Currently, no standardized assays have been developed as purchasable kits for HCV resistance testing. The aim of this study was to evaluate the performance of the Sentosa SQ HCV Genotyping Assay, a novel deep sequencing-based assay, to identify resistance-associated substitutions (RASs) in the NS3 protease, NS5A protein domain I and NS5B polymerase regions for patients infected with HCV genotypes-1a and 1b.

Methods: Serum samples collected from patients with chronic hepatitis C infection who failed to achieve a sustained virological response after receiving a DAA-containing treatment regimen were extracted and sequenced by two methods including population sequencing of the NS3, NS5A and NS5B coding region reference method and the deep sequencing-based Sentosa SQ HCV Genotyping Assay.

Results: A high concordance rate with Sanger sequencing, the reference method, was found for the NS3, NS5A and NS5 coding regions, regardless of the genotype-1 subtypes. The deep sequencing-based assay was more sensitive than population sequencing to detect minority variants, representing less than 10% of the viral populations, but also some variants representing up to 30% of the viral quasispecies, as expected.

Conclusions: The Sentosa SQ HCV Genotyping Assay can be confidently used in clinical practice in the indications of HCV resistance testing for these subtypes. Technical improvements are now required to allow for pangenotypic coverage.
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http://dx.doi.org/10.3851/IMP3318DOI Listing
July 2020

Prevalence of hepatitis C infection, screening and associated factors among men who have sex with men attending gay venues: a cross-sectional survey (PREVAGAY), France, 2015.

BMC Infect Dis 2019 Apr 11;19(1):315. Epub 2019 Apr 11.

Department of Infectious Diseases - Santé publique France, French national public health agency, 12 rue du Val d'Osne, 94415, Saint-Maurice, Cedex, France.

Background: Over the last 20 years, Hepatitis C virus (HCV) infection prevalence has dramatically increased among HIV-infected men who have sex with men (MSM) in many countries worldwide. It is suspected that this increase is primarily driven by sexual behaviours linked to blood exposure. Monitoring these behaviours is crucial to understand the drivers of the epidemic. This study assessed the prevalence of chronic HCV infection among MSM attending gay venues and associated chronic HCV risk factors. HCV screening and associated factors were described.

Methods: The cross-sectional survey PREVAGAY, based on time-location sampling, was conducted in 2015 among MSM attending gay venues in 5 French metropolitan cities. A self-administered questionnaire was completed and capillary whole blood on dried blood spots (DBS) collected. Possible factors associated with chronic HCV prevalence and with HCV screening in the previous year were investigated using Poisson regression.

Results: Chronic HCV infection prevalence from DBS analysis was 0.7% [IC95%: 0.3-1.5] in the study's 2645 participants and was 3.0% [1.5-5.8] in HIV-positive MSM. It was significantly higher in those who reported the following: (lifetime) slamming (with or without the sharing of injection equipment); (during the previous year) fisting and chemsex, unprotected anal intercourse with casual partners, using gay websites and/or of mobile-based GPS applications, and having more than 10 sexual partners. Only 41.3% [38.2-44.5] of the participants reported HCV screening during the previous year. Screening was significantly more frequent in MSM under 30 years of age, those who were HIV-positive, those vaccinated against hepatitis B and meningococcus C, and those who reported the following (during the previous year): more than 10 sexual partners, at least one sexually transmitted infection and fisting.

Conclusion: Chronic HCV infection prevalence in MSM attending gay venues was significantly higher in HIV-positive MSM and in those with risky sexual behaviours. Reflecting current screening recommendations for specific populations, previous HCV screening was more frequent in HIV-positive individuals and those with risky sexual behaviours. Nevertheless, HCV screening coverage needs to be improved in these populations. Comprehensive medical management, which combines screening and linkage to care with prevention strategies, is essential to control HCV among MSM.
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http://dx.doi.org/10.1186/s12879-019-3945-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458747PMC
April 2019

Strategies for the improvement of HCV testing and diagnosis.

Expert Rev Anti Infect Ther 2019 05 22;17(5):341-347. Epub 2019 Apr 22.

a National Reference Center for Viral Hepatitis B, C and delta, Department of Virology, Hôpital Henri Mondor , Université Paris-Est , Créteil , France.

: The improvement of number of people diagnosed with hepatitis C virus (HCV) infection is crucial to reach the WHO objectives for eliminating viral hepatitis by 2030. Alternatives to classical HCV virological tests using serum or plasma taken from venous puncture including point-of-care (POC) tests and dried blood spot (DBS) are being considered for HCV screening, diagnosis, and monitoring. Reflex nucleic acid testing and HCV core antigen test have the potential to simplify diagnostic algorithm, increase diagnosis and facilitate linkage to care. : This review examines strategies for the improvement of HCV testing and diagnosis including alternatives to classical HCV virological tests and approaches for simplified diagnostic algorithms. : Serological and molecular POC tests are now available for HCV antibody and HCV RNA detections in less than 20 and 60, respectively. DBS offers the main advantage to store desiccated blood that can be easily transported to reference centers where state-of-the-art molecular and serological diagnostic tests are used. Simplifications of diagnostic algorithms are urgently needed to enhance HCV testing, linkage to care and treatment.
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http://dx.doi.org/10.1080/14787210.2019.1604221DOI Listing
May 2019

High prevalence and poor linkage to care of transfusion-transmitted infections among blood donors in Dar-es-Salaam, Tanzania.

J Viral Hepat 2019 06 27;26(6):750-756. Epub 2019 Feb 27.

Department of Hepatology, Imperial College London, St Mary's Hospital, London, UK.

Blood transfusion is one of the most commonly relied upon therapies in sub-Saharan Africa. Existing safeguards recommended include systematic screening for transfusion-transmitted infections and restricted voluntary nonremunerated blood donor selection. We report the transfusion-transmitted infection screening and notification practice at a large urban blood transfusion centre in Dar-es-Salaam, Tanzania. Between October 2016 and March 2017 anonymized records of all donors registered at the blood transfusion unit were accessed to retrospectively note demographic information, donor status, first-time status, transfusion-transmitted infection result and notification. 6402 consecutive donors were screened for transfusion-transmitted infections; the majority were family/replacement blood donors (88.0%) and male (83.8%). Overall transfusion-transmitted infections prevalence was 8.4% (95% CI 7.8-9.1), with hepatitis B being the most prevalent infection (4.1% (95% CI 3.6-4.6)). Transfusion-transmitted infections were more common in family/replacement blood donors (9.0% (95% CI 8.3-9.8)) as compared to voluntary nonremunerated blood donor (4.1% (95% CI 2.8-5.7)). A minority of infected-donors were notified of a positive result (8.5% (95% CI 6.3-11.2)). Although transfusion-transmitted infections are more prevalent among family/replacement blood donors, overall risk of transfusion-transmitted infections across all groups is considerable. In addition, existing efforts to notify donors of a positive transfusion-transmitted infection are poor. Future policies must focus on improving linkage to care for newly diagnosed patients with transfusion-transmitted infections.
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http://dx.doi.org/10.1111/jvh.13073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563112PMC
June 2019

Antiviral activity of bone morphogenetic proteins and activins.

Nat Microbiol 2019 02 3;4(2):339-351. Epub 2018 Dec 3.

MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.

Understanding the control of viral infections is of broad importance. Chronic hepatitis C virus (HCV) infection causes decreased expression of the iron hormone hepcidin, which is regulated by hepatic bone morphogenetic protein (BMP)/SMAD signalling. We found that HCV infection and the BMP/SMAD pathway are mutually antagonistic. HCV blunted induction of hepcidin expression by BMP6, probably via tumour necrosis factor (TNF)-mediated downregulation of the BMP co-receptor haemojuvelin. In HCV-infected patients, disruption of the BMP6/hepcidin axis and genetic variation associated with the BMP/SMAD pathway predicted the outcome of infection, suggesting that BMP/SMAD activity influences antiviral immunity. Correspondingly, BMP6 regulated a gene repertoire reminiscent of type I interferon (IFN) signalling, including upregulating interferon regulatory factors (IRFs) and downregulating an inhibitor of IFN signalling, USP18. Moreover, in BMP-stimulated cells, SMAD1 occupied loci across the genome, similar to those bound by IRF1 in IFN-stimulated cells. Functionally, BMP6 enhanced the transcriptional and antiviral response to IFN, but BMP6 and related activin proteins also potently blocked HCV replication independently of IFN. Furthermore, BMP6 and activin A suppressed growth of HBV in cell culture, and activin A inhibited Zika virus replication alone and in combination with IFN. The data establish an unappreciated important role for BMPs and activins in cellular antiviral immunity, which acts independently of, and modulates, IFN.
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http://dx.doi.org/10.1038/s41564-018-0301-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590058PMC
February 2019

Primary resistance of hepatitis B virus to nucleoside and nucleotide analogues.

J Viral Hepat 2019 02 14;26(2):278-286. Epub 2018 Nov 14.

Department of Virology, Hôpital Henri Mondor, National Reference Center for Viral Hepatitis B, C and D, Université Paris-Est, Créteil, France.

Nucleoside and nucleotide analogues (NUCs) targeting hepatitis B virus are capable of selecting resistant viruses upon long-term administration as monotherapies. The prevalence of resistance-associated substitutions (RASs) and fitness-associated substitutions at baseline of NUC therapy and their impact on treatment responses remain unknown. A total of 232 treatment-naïve patients chronically infected with hepatitis B virus (HBV) consecutively referred for the first time to one of French reference centres were included. The nearly full-length HBV reverse transcriptase was sequenced by means of deep sequencing, and the sequences were analysed. RASs were detected in 25% of treatment-naïve patients, generally representing low proportions of the viral quasispecies. All amino acid positions known to be associated with HBV resistance to currently approved NUCs or with increased fitness of resistant variants were affected, except position 80. RASs at positions involved in lamivudine, telbivudine and adefovir resistance were the most frequently detected. All patients with RASs detectable by next-generation sequencing at baseline who were treatment-eligible and treated with currently recommended drugs achieved a virological response. The presence of pre-existing HBV RASs has no impact on the outcome of therapy if potent drugs with a high barrier to resistance are used.
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http://dx.doi.org/10.1111/jvh.13025DOI Listing
February 2019
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