Publications by authors named "Nina Weis"

102 Publications

Effect of PEP flute self-care versus usual care in early covid-19: non-drug, open label, randomised controlled trial in a Danish community setting.

BMJ 2021 11 24;375:e066952. Epub 2021 Nov 24.

Parker Institute, Copenhagen University Hospital Bispebjerg-Frederiksberg, Frederiksberg, Denmark.

Objective: To determine whether positive expiratory pressure (PEP) by PEP flute self-care is effective in reducing respiratory symptoms among community dwelling adults with SARS-CoV-2 infection and early stage covid-19.

Design: Non-drug, open label, randomised controlled trial.

Setting: Capital Region and Region Zealand in Denmark from 6 October 2020 to 26 February 2021.

Participants: Community dwelling adults, able to perform self-care, with a new SARS-CoV-2 infection (verified by reverse transcription polymerase chain reaction tests) and symptoms of covid-19.

Intervention: Participants were randomised to use PEP flute self-care in addition to usual care or have usual care only. Randomisation was based on permuted random blocks in a 1:1 ratio, stratified for sex and age (<60 or ≥60 years). The PEP self-care group was instructed to use a PEP flute three times per day during the 30 day intervention.

Main Outcome Measures: Primary outcome was a change in symptom severity from baseline to day 30, as assessed by the self-reported COPD (chronic obstructive pulmonary disease) assessment test (CAT), which was adjusted for baseline values and stratification factors. Participants completed the CAT test questionnaire every day online. Secondary outcomes were self-reported urgent care visits due to covid-19, number of covid-19 related symptoms, and change in self-rated health, all within 30-days' follow-up.

Results: 378 participants were assigned to the PEP flute self-care intervention (n=190) or usual care only (n=188). In the PEP self-care group, the median number of days with PEP flute use was 21 days (interquartile range 13-25). For the intention-to-treat population, a group difference was observed in changes from baseline in CAT scores of -1.2 points (95% confidence interval -2.1 to -0.2; P=0.017) in favour of the PEP flute self-care group. At day 30, the PEP flute self-care group also reported less chest tightness, less dyspnoea, more vigour, and higher level of daily activities, but these differences were small, and no consistent effects were seen on the secondary outcomes. No serious adverse events were reported.

Conclusions: In community dwelling adults with early covid-19, PEP flute self-care had a significant, yet marginal and uncertain clinical effect on respiratory symptom severity, as measured by CAT scores.

Trial Registration: ClinicalTrials.gov NCT04530435.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmj-2021-066952DOI Listing
November 2021

Hepatitis B virus elimination status and strategies in circumpolar countries, 2020.

Int J Circumpolar Health 2021 12;80(1):1986975

Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, US Centers for Disease Control and Prevention (CDC), Anchorage, Alaska, USA.

Hepatitis B virus (HBV) infection remains a global health threat. The World Health Organization (WHO) established a goal to eliminate HBV infection as a public health threat by 2030, and defined targets for key interventions to achieve that goal. We evaluated HBV burden and relevant national recommendations for progress towards WHO targets in circumpolar countries. Viral hepatitis experts of circumpolar countries were surveyed regarding their country's burden of HBV, achievement of WHO targets and national public health authority recommendations for HBV prevention and control. Eight of nine circumpolar countries responded. All countries continue to see new HBV infections. Data about HBV prevalence and progress in reaching WHO 2030 elimination targets are lacking. No country was able to report data for all seven WHO target measures. All countries have recommendations targeting the prevention of mother-to-child transmission. Only the USA and Greenland recommend universal birth dose vaccination. Four countries have recommendations to screen persons at high risk for HBV. Existing recommendations largely address prevention; however, recommendations for universal birth dose vaccination have not been widely introduced. Opportunities remain for the development of trackable targets and national elimination planning to screen and treat for HBV to reduce incidence and mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/22423982.2021.1986975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8530492PMC
December 2021

Neutralisation titres against SARS-CoV-2 are sustained 6 months after onset of symptoms in individuals with mild COVID-19.

EBioMedicine 2021 Sep 19;71:103519. Epub 2021 Aug 19.

Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address:

Background: Given the importance of neutralising antibodies in protection against SARS-CoV-2 infection, it is critical to assess neutralisation persistence long-term following recovery. This study investigated neutralisation titres against SARS-CoV-2 up to 6 months post-symptom onset in individuals with mild COVID-19.

Methods: Plasma neutralisation titres in convalescent COVID-19 individuals were determined at baseline and 6 months post-symptom onset using a cell culture infectious SARS-CoV-2 assay. Total SARS-CoV-2 spike-specific IgG and IgA binding was measured using a lectin capture ELISA and compared between timepoints and correlated to neutralising titres.

Findings: All 48 convalescent COVID-19 individuals were found to have detectable SARS-CoV-2 50% inhibitory dilution neutralisation titres (ID) at baseline and 6 months post-symptom onset with mean ID of 1/943 and 1/411, respectively. SARS-CoV-2 neutralisation titres peaked within 1-2 months post-symptom onset. However, 50% of individuals showed comparable ID at baseline and 6 months post-symptom onset. Both SARS-CoV-2 spike-specific IgG and IgA levels correlated well with neutralising titres. IgG binding was found to be sustained up to 6 months post-symptom onset, whereas IgA levels declined.

Interpretation: This study demonstrates durability of SARS-CoV-2 spike-specific IgG and neutralisation responses following recovery from mild COVID-19. Thus, all subjects included in this study might potentially have protective levels of neutralising antibodies 6 months post-symptom onset. This study also demonstrates a relationship between spike-specific IgA and neutralisation decline, with implications for long-term protection against SARS-CoV-2 infection.

Funding: Novo Nordisk Foundation, Independent Research Fund Denmark and Danish Agency for Science and Higher Education.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2021.103519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375401PMC
September 2021

Characterization of Fitness and Convalescent Antibody Neutralization of SARS-CoV-2 Cluster 5 Variant Emerging in Mink at Danish Farms.

Front Microbiol 2021 25;12:698944. Epub 2021 Jun 25.

Virus and Microbiological Special Diagnostics, Statens Serum Institut, Copenhagen, Denmark.

In addition to humans, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transmit to animals that include hamsters, cats, dogs, mink, ferrets, tigers, lions, cynomolgus macaques, rhesus macaques, and treeshrew. Among these, mink are particularly susceptible. Indeed, 10 countries in Europe and North America reported SARS-CoV-2 infection among mink on fur farms. In Denmark, SARS-CoV-2 spread rapidly among mink farms and spilled-over back into humans, acquiring mutations/deletions with unknown consequences for virulence and antigenicity. Here we describe a mink-associated SARS-CoV-2 variant (Cluster 5) characterized by 11 amino acid substitutions and four amino acid deletions relative to Wuhan-Hu-1. Temporal virus titration, together with genomic and subgenomic viral RNA quantitation, demonstrated a modest fitness attenuation of the Cluster 5 virus in the Vero-E6 cell line. Potential alterations in antigenicity conferred by amino acid changes in the spike protein that include three substitutions (Y453F, I692V, and M1229I) and a loss of two amino acid residues 69 and 70 (ΔH69/V70), were evaluated in a virus microneutralization assay. Compared to a reference strain, the Cluster 5 variant showed reduced neutralization in a proportion of convalescent human COVID-19 samples. The findings underscore the need for active surveillance SARS-CoV-2 infection and virus evolution in susceptible animal hosts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2021.698944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267889PMC
June 2021

The Danish HIV Birth Cohort (DHBC) - a nationwide, prospective cohort.

BMJ Open 2021 07 8;11(7):e044565. Epub 2021 Jul 8.

Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.

Purpose: The purpose of the Danish HIV Birth Cohort (DHBC) is to investigate the significance of HIV-1 infection in pregnancy and after delivery in women living with HIV (WLWH) in Denmark and their children, in the era of antiretroviral therapy and other interventions for treatment and prophylaxis.

Participants: All WLWH giving birth to one or more children in Denmark after 31 December 1999 are included, with consecutive ongoing enrolment, if they are living with HIV and pregnant, or if they are diagnosed with HIV in relation to pregnancy, delivery or shortly after delivery.

Findings To Date: DHBC has been used to describe trends in the management of pregnancies in WLWH and their outcomes on a nationwide basis, mode of delivery and predictors of emergency caesarean section as well as risk factors during pregnancy in WLWH for birth-related complications compared with women from the general population (WGP). We have found that HIV-exposed, but uninfected (HEU) children born to WLWH had a lower median birth weight and gestational age and were at higher risk of intrauterine growth retardation than children born to WGP. We have investigated risk of in-hospital admission and use of antibiotics during the first 4 years of life among HEU children and showed that HEU children had an increased risk of overall hospital admission compared with a matched control group of unexposed children.Further, we compared anthropometric outcomes in children with a matched control group of children not exposed to HIV.

Future Plans: To continuously investigate the significance of HIV infection and antiretroviral therapy in pregnancy and after delivery in WLWH in Denmark and their HEU children and compare these findings with children born to WGP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-044565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268920PMC
July 2021

PEP-CoV protocol: a PEP flute-self-care randomised controlled trial to prevent respiratory deterioration and hospitalisation in early COVID-19.

BMJ Open 2021 06 30;11(6):e050582. Epub 2021 Jun 30.

Research Unit for Dietary Studies, The Parker Institute, Frederiksberg, Copenhagen University Hospital, Frederiksberg, Denmark.

Introduction: Infection with SARS-CoV-2 may progress to severe pulmonary disease, COVID-19. Currently, patients admitted to hospital because of COVID-19 have better prognosis than during the first period of the pandemic due to improved treatment. However, the overall societal susceptibility of being infected makes it pivotal to prevent severe courses of disease to avoid high mortality rates and collapse of the healthcare systems. Positive expiratory pressure (PEP) self-care is used in chronic pulmonary disease and has been shown to prevent pneumonia in a high-risk cohort of patients with leukaemia. PEP flute self-care to prevent respiratory deterioration and hospitalisation in early COVID-19: a randomised trial (The PEP-CoV trial) examines the effectiveness on respiratory symptoms and need of hospital admission by regular PEP flute use among non-hospitalised individuals with confirmed SARS-CoV-2 infection and COVID-19 symptoms.

Methods And Analysis: In this randomised controlled trial, we hypothesise that daily PEP flute usage as add-on to usual care is superior to usual care as regards symptom severity measured by the COPD Assessment Test (CAT) at 30-day follow-up (primary outcome) and hospital admission through register data (secondary outcome). We expect to recruit 400 individuals for the trial. Participants in the intervention group receive a kit of 2 PEP flutes and adequate resistances and access to instruction videos. A telephone hotline offers possible contact to a nurse. The eight-item CAT score measures cough, phlegm, chest tightness, dyspnoea, activities of daily living at home, feeling safe at home despite symptoms, sleep quality and vigour. The CAT score is measured daily in both intervention and control arms by surveys prompted through text messages.

Ethics And Dissemination: The study was registered prospectively at www.clinicaltrials.gov on 27 August 2020 (NCT04530435). Ethical approval was granted by the local health research ethics committee (Journal number: H-20035929) on 23 July 2020. Enrolment of participants began on 6 October 2020. Results will be published in scientific journals.

Trial Registration Number: NCT04530435; Pre-results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2021-050582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249175PMC
June 2021

Overcoming Culture Restriction for SARS-CoV-2 in Human Cells Facilitates the Screening of Compounds Inhibiting Viral Replication.

Antimicrob Agents Chemother 2021 06 17;65(7):e0009721. Epub 2021 Jun 17.

Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark.

Efforts to mitigate the coronavirus disease 2019 (COVID-19) pandemic include the screening of existing antiviral molecules that could be repurposed to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Although SARS-CoV-2 replicates and propagates efficiently in African green monkey kidney (Vero) cells, antivirals such as nucleos(t)ide analogs (NUCs) often show decreased activity in these cells due to inefficient metabolization. SARS-CoV-2 exhibits low viability in human cells in culture. Here, serial passages of a SARS-CoV-2 isolate (original-SARS2) in the human hepatoma cell clone Huh7.5 led to the selection of a variant (adapted-SARS2) with significantly improved infectivity in human liver (Huh7 and Huh7.5) and lung cancer (unmodified Calu-1 and A549) cells. The adapted virus exhibited mutations in the spike protein, including a 9-amino-acid deletion and 3 amino acid changes (E484D, P812R, and Q954H). E484D also emerged in Vero E6-cultured viruses that became viable in A549 cells. Original and adapted viruses were susceptible to scavenger receptor class B type 1 (SR-B1) receptor blocking, and adapted-SARS2 exhibited significantly less dependence on ACE2. Both variants were similarly neutralized by COVID-19 convalescent-phase plasma, but adapted-SARS2 exhibited increased susceptibility to exogenous type I interferon. Remdesivir inhibited original- and adapted-SARS2 similarly, demonstrating the utility of the system for the screening of NUCs. Among the tested NUCs, only remdesivir, molnupiravir, and, to a limited extent, galidesivir showed antiviral effects across human cell lines, whereas sofosbuvir, ribavirin, and favipiravir had no apparent activity. Analogously to the emergence of spike mutations , the spike protein is under intense adaptive selection pressure in cell culture. Our results indicate that the emergence of spike mutations will most likely not affect the activity of remdesivir.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.00097-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406809PMC
June 2021

Prevalence and association with birth outcomes of low vitamin D levels among pregnant women living with HIV.

AIDS 2021 07;35(9):1491-1496

Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre.

Objectives: To evaluate the prevalence of low vitamin D levels among well treated pregnant women living with HIV (WLWH) on combination antiretroviral therapy in Denmark, to identify risk factors of low vitamin D levels, and to assess the association between vitamin D status and birth outcomes.

Design: Nationwide cohort study.

Methods: All WLWH in Denmark giving birth from 2000 to 2018 with a vitamin D measurement during pregnancy were identified. Risk factors for low vitamin D (deficiency or insufficiency) were assessed using log-binomial regression models, both univariate and adjusted for maternal and HIV factors. The association between vitamin D status and birth outcomes was assessed using linear regression models for continuous outcomes and log-binomial models for binary outcomes.

Results: Among 208 WLWH, the prevalence of vitamin D deficiency was 13%, insufficiency 34%, and sufficiency 53%. Being of African origin (RR 2.68, P = 0.01), Asian origin (RR 3.38, P = < 0.01), or having HIV RNA levels more than 50 copies/ml (RR 1.43, P = 0.04) was associated with an increased risk of low vitamin D level. WLWH with vitamin D deficiency had an increased risk of preterm birth (RR 2.66, P = 0.03) and giving birth to small for gestational age (SGA) children (RR 6.83, P = 0.02) compared with WLWH with sufficient vitamin D level.

Conclusion: Low vitamin D level was prevalent among well treated pregnant WLWH in Denmark, especially among women of African or Asian origin, and women with detectable viral loads. Vitamin D deficiency was associated with an increased risk of preterm birth and SGA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAD.0000000000002899DOI Listing
July 2021

Low incidence of HCC in chronic hepatitis C patients with pretreatment liver stiffness measurements below 17.5 kilopascal who achieve SVR following DAAs.

PLoS One 2020 10;15(12):e0243725. Epub 2020 Dec 10.

Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.

Background And Aims: To evaluate the ability of pretreatment liver stiffness measurements (pLSM) to predict hepatocellular carcinoma (HCC), incident decompensation and all-cause mortality in chronic hepatitis C (CHC) patients who achieved sustained virological response (SVR) after treatment with direct-acting antivirals (DAAs).

Methods: 773 CHC patients with SVR after DAA treatment and no prior liver complications were identified retrospectively. Optimized cut-off of 17.5 kPa for incident HCC was selected by maximum Youden's index. Patients were grouped by pLSM: <10 kPa [reference], 10-17.4 kPa and ≥17.5 kPa. Primary outcomes were incident hepatocellular carcinoma and secondary outcomes were incident decompensated cirrhosis and all-cause mortality, analyzed using cox-regression.

Results: Median follow-up was 36 months and 43.5% (336) had cirrhosis (LSM>12.5 kPa). The median pLSM was 11.6 kPa (IQR 6.7-17.8, range 2.5-75) and pLSM of <10 kPa, 10-17.4 kPa and 17.5-75 kPa was seen in 41.5%, 32.2% and 26.3%. During a median follow-up time of 36 months, 11 (1.4%) developed HCC, 14 (1.5%) developed decompensated cirrhosis, and 38 (4.9%) patients died. A pLSM of 17.5 kPa identified patients with a high risk of HCC with a negative predictive value of 98.9% and incidence rate of HCC in the 17.5-75 kPa group of 1.40/100 person years compared to 0.14/100 person years and 0.12/100 person years in the 10-17.4 kPa and <10 kPa groups, p<0.001.

Conclusion: Pretreatment LSM predicts risk of HCC, decompensation and all-cause mortality in patients with SVR after DAA treatment. Patients with a pLSM <17.5 kPa and no other risk factors for chronic liver disease appear not to benefit from HCC surveillance for the first 3 years after treatment. Longer follow-up is needed to clarify if they can be safely excluded from post treatment HCC screening hereafter.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243725PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728240PMC
January 2021

The Copenhagen test and treat hepatitis C in a mobile clinic study: a protocol for an intervention study to enhance the HCV cascade of care for people who inject drugs (T'N'T HepC).

BMJ Open 2020 11 9;10(11):e039724. Epub 2020 Nov 9.

Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.

Introduction: Injecting drug use is the primary driver of hepatitis C virus (HCV) infection in Europe. Despite the need for more engagement with care, people who inject drugs (PWID) are hard to reach with HCV testing and treatment. We initiated a study to evaluate the efficacy for testing and linkage to care among PWID consulting peer-based testing at a mobile clinic in Copenhagen, Denmark.

Methods And Analysis: In this intervention study, we will recruit participants at a single community-based, peer-run mobile clinic. In a single visit, we will first offer participants a point-of-care HCV antibody test, and if they test positive, then they will receive an HCV RNA test. If they are HCV-RNA+, we will administer facilitated referrals to designated 'fast-track' clinics at a hospital or an addiction centre for treatment. The primary outcomes for this study are the number of tested and treated individuals. Secondary outcomes include individuals lost at each step in the care cascade.

Ethics And Dissemination: The results of this study could provide a model for targeting PWID for HCV testing and treatment in Demark and other settings, which could help achieve WHO HCV elimination targets. The Health Research Ethics Committee of Denmark and the Danish Data Protection Agency confirmed (December 2018/January 2019) that this study did not require their approval. Study findings will be disseminated through peer-reviewed publications, conference presentations and social media.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-039724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654134PMC
November 2020

Global evolutionary analysis of chronic hepatitis C patients revealed significant effect of baseline viral resistance, including novel non-target sites, for DAA-based treatment and retreatment outcome.

J Viral Hepat 2021 02 25;28(2):302-316. Epub 2020 Nov 25.

Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.

Direct-acting antivirals (DAAs) have proven highly effective against chronic hepatitis C virus (HCV) infection. However, some patients experience treatment failure, associated with resistance-associated substitutions (RASs). Our aim was to investigate the complete viral coding sequence in hepatitis C patients treated with DAAs to identify RASs and the effects of treatment on the viral population. We selected 22 HCV patients with sustained virologic response (SVR) to match 21 treatment-failure patients in relation to HCV genotype, DAA regimen, liver cirrhosis and previous treatment experience. Viral-titre data were compared between the two patient groups, and HCV full-length open reading frame deep-sequencing was performed. The proportion of HCV NS5A-RASs at baseline was higher in treatment-failure (82%) than matched SVR patients (25%) (p = .0063). Also, treatment failure was associated with slower declines in viraemia titres. Viral population diversity did not differ at baseline between SVR and treatment-failure patients, but failure was associated with decreased diversity probably caused by selection for RAS. The NS5B-substitution 150V was associated with sofosbuvir treatment failure in genotype 3a. Further, mutations identified in NS2, NS3-helicase and NS5A-domain-III were associated with DAA treatment failure in genotype 1a patients. Six retreated HCV patients (35%) experienced 2nd treatment failure; RASs were present in 67% compared to 11% with SVR. In conclusion, baseline RASs to NS5A inhibitors, but not virus population diversity, and lower viral titre decline predicted HCV treatment failure. Mutations outside of the DAA targets can be associated with DAA treatment failure. Successful DAA retreatment in patients with treatment failure was hampered by previously selected RASs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jvh.13430DOI Listing
February 2021

Prevalence of herpes -, measles morbillivirus-, parvovirus B19 - and rubella viruses immunoglobulin G among women with chronic hepatitis B of reproductive age in Denmark: A cross-sectional study.

Int J Infect Dis 2020 Dec 1;101:269-275. Epub 2020 Oct 1.

Department of Infectious Diseases, Copenhagen University Hospital Hvidovre, Kettegaard Alle 30, DK 2650 Hvidovre, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK 2200 Copenhagen, Denmark. Electronic address:

Objectives: The aim of this study was to investigate whether the seroprevalence of IgG antibodies against seven viruses (cytomegalovirus, herpes simplex virus 1&2, measles morbillivirus, parvovirus B19, rubella, and varicella-zoster virus), which can potentially compromise maternal and fetal wellbeing, differs based on country of origin among women with chronic hepatitis B (CHB).

Method: This study was a single-center, hospital-based cross-sectional study. The study included women with CHB 15-45 years of age, included in the Danish Database for Hepatitis B and C. Seroprevalence estimates were calculated with a 95% confidence interval and were compared between age groups, regions of origin, and to the general population.

Results: 177 women were included in the study. Overall, the seroprevalences of antibodies were similar among women with CHB with origin outside Denmark and compared to the general population in Denmark, but there was a notable difference in the seroprevalence of antibodies against herpes simplex 2 between women from Africa (37.1% CI 95% 22.0;55.1) and women from the Middle East (2.5% CI 95% 0.1;14.7).

Conclusion: Women with CHB whose origin is outside Denmark do not appear to differ, based on origin, or be at greater risk of acquiring these viruses during pregnancy than their Danish counterparts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2020.09.1477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817472PMC
December 2020

Hepatitis C prevalence in Denmark in 2016-An updated estimate using multiple national registers.

PLoS One 2020 3;15(9):e0238203. Epub 2020 Sep 3.

Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.

Background: Chronic hepatitis C (CHC) can be eliminated as a public health threat by meeting the WHO targets: 90% of patients diagnosed and 80% treated by 2030. To achieve and monitor progress towards elimination, an updated estimate of the size of the CHC population is needed, but Denmark has no complete national CHC register. By combining existing registers in 2007, we estimated the population living with CHC to be 16,888 (0.38% of the adult population).

Aim: To estimate the population living with diagnosed and undiagnosed CHC in Denmark on 31 December 2016. Among additional aims were to estimate the proportion of patients attending specialised clinical care.

Methods: People with diagnosed CHC were identified from four national registers. The total diagnosed population was estimated by capture-recapture analysis. The undiagnosed population was estimated by comparing the register data with data from two cross-sectional surveys.

Results: The population living with diagnosed CHC in Denmark was 7,581 persons (95%CI: 7,416-12,661) of which 6,116 (81%) were identified in the four registers. The estimated undiagnosed fraction was 24%, so the total CHC infected population was 9,975 corresponding to 0.21% of the adult population (95%CI: 9,758-16,659; 0.21%-0.36%). Only 48% of diagnosed patients had received specialised clinical care.

Conclusion: CHC prevalence in Denmark is declining and 76% of patients have been diagnosed. Linking diagnosed patients to care and increasing efforts to test people with former or current drug use will be necessary to achieve CHC elimination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238203PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470322PMC
October 2020

[The endocrine and metabolic link between COVID-19, diabetes and obesity].

Ugeskr Laeger 2020 07;182(29)

Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome corona virus 2. High age, hypertension, diabetes, and obesity are risk factors for severe COVID-19 with increased mortality. In this review, we discuss potential mechanisms by which diabetes and obesity modulate the host viral interactions and host-immune response. Glucose levels should be monitored rigorously, and patient-tailored aggressive treatment of hyperglycaemia is recommended, often with the use of insulin. Persons with diabetes and obesity are susceptible to severe outcomes from COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
July 2020

Implementation of treatment recommendations for chronic hepatitis B in patients attending specialized hospital care in Denmark - a region wide study.

Scand J Gastroenterol 2020 Jul 22;55(7):843-847. Epub 2020 Jun 22.

Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.

To evaluate implementation of national guideline recommendations on treatment initiation for chronic hepatitis B (CHB) in Denmark. Using DANHEP, a nationwide cohort of chronic hepatitis B and C patients attending specialized hospital care in Denmark, we performed a descriptive cohort study from January 2002 through December 2017. We identified patients with CHB in 3 of 5 Danish regions, with at least two hospital/outpatient clinic visits during the study period. We identified 990 CHB patients who remained untreated throughout the study period, and 265 who initiated treatment. At their last visit 952/990 (96%, 95% CI 95-97) untreated patients did not meet current national criteria for treatment initiation while 198/265 (75%, 95% CI 69-80) who initiated treatment met the national criteria. Overall, 198/236 (84%, 95% CI 79-88) who met national treatment criteria, initiated treatment. The majority of CHB patients received care in line with national guideline recommendations for treatment initiation. We found that only few patients eligible for treatment remained untreated. However, a fourth of patients who received treatment were not eligible according to national guidelines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00365521.2020.1779803DOI Listing
July 2020

[Elimination of hepatitis C virus in Denmark].

Ugeskr Laeger 2020 02;182(9)

In Denmark, about 50% of patients with chronic hepatitis C virus (HCV) infection are undiagnosed. Since 2014, therapy containing direct-acting antivirals (DAA) has proven efficient and is available to all patients, who have a chronic HCV infection and a Danish personal identification number. The World Health Organization has a goal of elimination of viral hepatitis in 2030. Elimination of HCV in Denmark should focus on reducing HCV transmission, incidence and prevalence, combined with treatment with DAA of all infected patients. Micro-elimination strategies may play a major role, but a national strategy is lacking.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2020

Study protocol: becoming and being a mother living with HIV - a multicentre longitudinal mixed methods study among pregnant women living with HIV, non-pregnant women living with HIV and pregnant women not living with HIV in a high-income setting (the 2B MOM study).

BMJ Open 2019 10 15;9(10):e027761. Epub 2019 Oct 15.

Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.

Introduction: The success of combination antiretroviral therapy has decreased the risk of perinatal HIV transmission and normalised pregnancy in women living with HIV (WLWH). Despite these advances, WLWH still face complex medical and psychosocial issues during pregnancy and postpartum, and there is a gap of knowledge on the experiences of becoming and being a mother living with HIV in today's context. The overall aim of this study is to investigate psychosocial outcomes and experiences of WLWH in Scandinavia during pregnancy and early motherhood.

Methods And Analysis: This is a multicentre longitudinal convergent mixed methods study consisting of a quantitative survey study, a qualitative interview study and a mixed methods analysis. The survey study aims to examine psychosocial outcomes of WLWH across the pregnancy - postpartum trajectory. Participants are pregnant WLWH living in Scandinavia. Two control groups of HIV-negative pregnant women and non-pregnant WLWH are also included. Data is collected in the third trimester, 3 and 6 months postpartum using standardised questionnaires. Statistical analysis will assess changes over time and identify predictors of adverse outcomes. The interview study seeks to understand experiences of pregnancy and becoming a mother while living with HIV. Pregnant WLWH who are enrolled in the survey study will be asked to participate in individual interviews in the third trimester and 6 months postpartum. Data will be analysed using narrative analysis. The survey and interview results will be merged in a mixed methods analysis to assess confirmation, expansion or discordance between the data sets.

Ethics And Dissemination: Approval from the Danish Data Protection Agency (VD-2018-253), and the Finnish and Swedish Ethics Committees have been obtained (HUS/1330/2019 and Dnr: 2019-04451, respectively). Study results will be disseminated to patient organisations, through publications in peer-reviewed journals and at scientific conferences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2018-027761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797316PMC
October 2019

The Consensus Hepatitis C Cascade of Care: Standardized Reporting to Monitor Progress Toward Elimination.

Clin Infect Dis 2019 11;69(12):2218-2227

Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain.

Cascade-of-care (CoC) monitoring is an important component of the response to the global hepatitis C virus (HCV) epidemic. CoC metrics can be used to communicate, in simple terms, the extent to which national and subnational governments are advancing on key targets, and CoC findings can inform strategic decision-making regarding how to maximize the progression of individuals with HCV to diagnosis, treatment, and cure. The value of reporting would be enhanced if a standardized approach were used for generating CoCs. We have described the Consensus HCV CoC that we developed to address this need and have presented findings from Denmark, Norway, and Sweden, where it was piloted. We encourage the uptake of the Consensus HCV CoC as a global instrument for facilitating clear and consistent reporting via the World Health Organization (WHO) viral hepatitis monitoring platform and for ensuring accurate monitoring of progress toward WHO's 2030 hepatitis C elimination targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciz714DOI Listing
November 2019

Incidence, prevalence and risk factors for hepatitis C in Danish prisons.

PLoS One 2019 26;14(7):e0220297. Epub 2019 Jul 26.

Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.

Hepatitis C virus (HCV) infection is prevalent among people in prison and prisons could therefore represent a unique opportunity to test risk groups for HCV. The aim of this sero-epidemiological study was to determine the incidence and prevalence of HCV infection and the corresponding risk factors in Danish prisons. Participants, recruited from eight Danish prisons, were tested for HCV using dried blood spots and filled out a questionaire with demographic data and risk factors for HCV infection. In total, 76.9% (801/1041) of all eligible prisoners consented to participate. The prevalence of HCV RNA positive prisoners was 4.2% (34/801) and the in-prison incidence rate was 0.7-1.0 per 100PY overall and 18-24/100PY among PWIDs. Infected prisoners were older than the overall population with a mean age of 42 years and only 17.6% (6/34) were younger than 35 years. The prevalence of PWID was 8.5% (68/801) and only 3% (2/68) of PWID were younger than 25 years. Among the PWID, 85.3% (58/68) had ever received opioid substitution therapy (OST) and 47.1% (32/68) were currently receiving OST. Risk factors associated with HCV infection were intravenous drug use, age ≥ 40 years, and being incarcerated ≥ 10 years. In conclusion, the prevalence of PWID in Danish prisons is low, possibly reflecting a decrease in injecting among the younger generation. This together with OST coverage could explain the low prevalence of HCV infection. However among PWIDs in prison the incidence remains high, suggesting a need for improved HCV prevention in prison.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0220297PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660074PMC
February 2020

Too many people with viral hepatitis are diagnosed late - with dire consequences.

Nat Rev Gastroenterol Hepatol 2019 08;16(8):451-452

Liver Unit, Vall d'Hebron Hospital, Barcelona, Spain.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41575-019-0177-zDOI Listing
August 2019

Children Exposed or Unexposed to Human Immunodeficiency Virus: Weight, Height, and Body Mass Index During the First 5 Years of Life-A Danish Nationwide Cohort.

Clin Infect Dis 2020 05;70(10):2168-2177

Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre.

Background: Exposures to human immunodeficiency (HIV) and antiretroviral therapy in utero may have adverse effects on infant growth. Among children born in Denmark and aged 0-5 years, we aimed to compare anthropometric outcomes in HIV-exposed but uninfected (HEU) children with those in children not exposed to HIV.

Methods: In a nationwide register-based study we included all singleton HEU children born in Denmark in 2000-2016. HEU children were individually matched by child sex, parity, and maternal place of birth to 5 singleton controls born to mothers without HIV. Weight-for-age z (WAZ) scores, length-for-age z (LAZ) scores, and weight-for-length or body mass index-for-age z scores were generated according to the World Health Organization standards and the Fenton growth chart for premature infants. Differences in mean z scores were analyzed using linear mixed models, both univariate and adjusted for social and maternal factors.

Results: In total, 485 HEU children and 2495 HIV-unexposed controls were included. Compared with controls, HEU children were smaller at birth, with an adjusted difference in mean WAZ and LAZ scores of -0.29 (95% confidence interval [CI], -.46 to -.12) and -0.51 (95% CI, -.71 to -.31), respectively (both P ≤ .001). Over time, there was a trend toward increasing WAZ and LAZ scores in HEU children, and there was no significant difference in adjusted WAZ scores after age 14 days (-0.13 [95% CI, -.27 to .01]; P = .07) and LAZ scores after age 6 months (-0.15 [95% CI, -.32 to .02]; P = .08).

Conclusion: Compared with a matched control group, HEU children were smaller at birth, but this difference decreased with time and is not considered to have a negative effect on the health and well-being of HEU children during early childhood.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciz605DOI Listing
May 2020

Hepatitis E during pregnancy: Maternal and foetal case-fatality rates and adverse outcomes-A systematic review.

J Viral Hepat 2019 11 14;26(11):1240-1248. Epub 2019 Jun 14.

Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.

Hepatitis E virus infection during pregnancy can have severe consequences for mother and child, such as vertical transmission, fulminant hepatic failure, even foetal or maternal mortality. The aim of this systematic review is to describe maternal, foetal and neonatal case-fatality rates as well as the prevalence of adverse outcomes in relation to hepatitis E virus infection during pregnancy. A systematic literature search was performed in Pubmed, Embase, Cochrane and CINAHL. Search terms included Pregnant, Women, Maternal, Infant, Foetal, Neonatal and Hepatitis E virus. Data were extracted using predefined data collection forms. All studies were quality assessed, either by the Newcastle-Ottawa Scale or by an adapted assessment scale for cross-sectional studies. We found 23 eligible studies, all observational, which were included in this systematic review with a total of 1338 cases. The median maternal, foetal and neonatal case-fatality rates were 26% (IQR 17%-41%), 33% (IQR 19%-37%) and 8% (IQR 3%-20%), respectively. Adverse outcomes such as fulminant hepatic failure, preterm labour, postpartum haemorrhage, low birth weight and vertical transmission were reported. The two studies that reported the highest prevalence of fulminant hepatic failure also reported the highest case-fatality rates. The median prevalence of fulminant hepatic failure was 45.3%. This systematic review found a high case-fatality rate among pregnant women infected with hepatitis E virus and a high rate of adverse outcomes among these women and their children. The results from this review mainly apply to hospital settings and symptomatic pregnant women from endemic countries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jvh.13129DOI Listing
November 2019

Evolutionary Pathways to Persistence of Highly Fit and Resistant Hepatitis C Virus Protease Inhibitor Escape Variants.

Hepatology 2019 09 5;70(3):771-787. Epub 2019 Jun 5.

Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Protease inhibitors (PIs) are important components of treatment regimens for patients with chronic hepatitis C virus (HCV) infection. However, emergence and persistence of antiviral resistance could reduce their efficacy. Thus, defining resistance determinants is highly relevant for efforts to control HCV. Here, we investigated patterns of PI resistance-associated substitutions (RASs) for the major HCV genotypes and viral determinants for persistence of key RASs. We identified protease position 156 as a RAS hotspot for genotype 1-4, but not 5 and 6, escape variants by resistance profiling using PIs grazoprevir and paritaprevir in infectious cell culture systems. However, except for genotype 3, engineered 156-RASs were not maintained. For genotypes 1 and 2, persistence of 156-RASs depended on genome-wide substitution networks, co-selected under continued PI treatment and identified by next-generation sequencing with substitution linkage and haplotype reconstruction. Persistence of A156T for genotype 1 relied on compensatory substitutions increasing replication and assembly. For genotype 2, initial selection of A156V facilitated transition to 156L, persisting without compensatory substitutions. The developed genotype 1, 2, and 3 variants with persistent 156-RASs had exceptionally high fitness and resistance to grazoprevir, paritaprevir, glecaprevir, and voxilaprevir. A156T dominated in genotype 1 glecaprevir and voxilaprevir escape variants, and pre-existing A156T facilitated genotype 1 escape from clinically relevant combination treatments with grazoprevir/elbasvir and glecaprevir/pibrentasvir. In genotype 1 infected patients with treatment failure and 156-RASs, we observed genome-wide selection of substitutions under treatment. Conclusion: Comprehensive PI resistance profiling for HCV genotypes 1-6 revealed 156-RASs as key determinants of high-level resistance across clinically relevant PIs. We obtained in vitro proof of concept for persistence of highly fit genotype 1-3 156-variants, which might pose a threat to clinically relevant combination treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.30647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6772116PMC
September 2019

The Prevalence of Human Immunodeficiency Virus Coinfection Among Patients Newly Diagnosed With Chronic Hepatitis B or C in Denmark: A Nationwide Cohort Study.

Open Forum Infect Dis 2018 Dec 21;5(12):ofy310. Epub 2018 Nov 21.

Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.

Background: Early identification of patients with chronic viral hepatitis coinfected with human immunodeficiency virus (HIV) is essential for optimal care. The objectives of this study were to estimate the prevalence of HIV coinfection among patients newly diagnosed with chronic viral hepatitis, HIV testing prevalence, and identify factors associated with coinfection.

Methods: Patients with chronic viral hepatitis newly enrolled in The Danish Database for Hepatitis B and C between 2002 and 2015 were identified. The HIV coinfection prevalence was calculated, and risk factors associated with HIV coinfection were estimated by logistic regression.

Results: In total, 8490 patients were included: 3091 had chronic hepatitis B (CHB), 5305 had chronic hepatitis C (CHC), and 94 had CHB and CHC. The prevalence of HIV coinfection was 4.4% (95% confidence interval [CI], 4.0-4.9) and was higher among CHC and CHB-CHC patients than CHB patients with a prevalence of 5.3% (95% CI, 4.7-5.9), 6.4% (95% CI, 2.4-13.4), and 2.9 (95% CI, 2.3-3.5), respectively ( < .0001). The HIV testing prevalence increased from 65% to 88% between 2002 and 2014 concurrently with a decrease in the HIV coinfection prevalence from 7.8% (95% CI, 5.5-10.7) to 1.6% (95% CI, 0.7-3.2). Age 35-50 years, male sex, and sexual route of viral hepatitis transmission were associated with HIV coinfection with odds ratios of 4.42 (95% CI, 1.40-13.94), 2.21 (95% CI, 1.74-2.81), and 8.81 (95% CI, 6.30-12.33), respectively.

Conclusions: The prevalence of HIV coinfection among patients with newly diagnosed chronic viral hepatitis decreased concurrently with an increase in HIV testing prevalence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ofid/ofy310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297860PMC
December 2018

Determination of anti-HCV and quantification of HCV-RNA and IP-10 from dried blood spots sent by regular mail.

PLoS One 2018 31;13(7):e0201629. Epub 2018 Jul 31.

Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.

Background: With the introduction of direct acting antivirals, treatment of hepatitis C virus (HCV) in hard-to-reach populations is now feasible. Therefore, new cost-effective and reliable test methods are needed. Determination of HCV antibodies and HCV-RNA from dried blood spots samples could represent one such method. Here we examined whether anti-HCV could be detected-and HCV-RNA quantified-from dried blood spots, sent by regular mail. We also investigated, if IP-10 determined from dried blood spots correlated with fibrosis progression appraised by transient elastography.

Method: Forty chronic HCV infected patients were consecutively enrolled. At baseline and after six months, dried blood spots were prepared from blood collected by venous puncture, dried for 4-6 hours, then stored in gas-impermeable plastic bags with a desiccator, before being sent by regular mail. At each visit, approximately six months apart, paired venous samples was obtained and analyzed for anti-HCV, HCV-RNA and IP-10.

Results: Anti-HCV was found in 66/67 of the dried blood spots. Sixty-six paired samples were available for HCV-RNA analysis. A statistically significant correlation was found between log HCV-RNA concentrations in plasma, and log HCV-RNA obtained from (P < 0.0001, Pearson's R 0.6788, R2 0.4607). HCV-RNA, derived from DBS samples, was lower than the corresponding plasma concentration, reflected by a Bland-Altman bias of 3 with SD of bias ± 0.6472. We found no correlation between IP-10 and fibrosis progression.

Conclusions: We identified anti-HCV in 66/67samples, and quantified IP-10 and HCV-RNA from dried blood spots, dried at room temperature and sent by regular mail. HCV-RNA concentrations from the dried blood spots were lower than corresponding plasma values; a probable result of heparin coated test tubes. We found no correlation between IP-10 and fibrosis progression. Overall, dried blood spots could be a cost-effective and easy-to-use alternative to standard tests for the diagnosis of HCV infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0201629PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067740PMC
February 2019

Outcome and adverse events in patients with chronic hepatitis C treated with direct-acting antivirals: a clinical randomized study.

Eur J Gastroenterol Hepatol 2018 10;30(10):1177-1186

Departments of Infectious Diseases.

Objective: New potent direct-acting antiviral (DAA) regimens against hepatitis C virus have been approved in recent years. However, information about the rate of adverse events (AEs) across different DAA regimens is limited. We aimed to evaluate differences in AEs and treatment efficacy in patients with chronic hepatitis C (CHC), genotype (GT) 1 or 3, randomized to two different treatment arms, correspondingly.

Patients And Methods: We randomly assigned 96 patients in a 1 : 1 ratio, to treatment for 12 weeks with either paritaprevir/ombitasvir/ritonavir/dasabuvir/ribavirin (RBV) or ledipasvir/sofosbuvir (SOF)/RBV if infected with GT1 (72 patients) or to daclatasvir/SOF/RBV for 12 weeks or SOF/RBV for 24 weeks, if infected with GT3 (24 patients). Data on AEs were collected throughout the entire study period.

Results: A total of 70 (97%) patients with CHC with GT1 and 20 (83%) patients with GT3 achieved cure. The GT3 treatment arm was prematurely terminated, owing to change in national treatment guidelines. Thus, only AEs for GT1 patients are described. AEs occurred in 70 (97%) GT1 patients, and most common AEs were anemia (n=56/78%), fatigue (n=53/74%), and headache (n=33/46%). No difference was observed in relation to treatment group (P=1.0), anemia (P=1.0), or liver cirrhosis (P=0.53). In seven (11%) patients, AEs assessed by the investigator to be possibly related to the DAA regimen were still present 12 weeks after treatment.

Conclusions: We found no difference in AEs possibly related to the DAA regimen in patients with CHC, but surprisingly, AEs possibly related to the DAA regimen persisted in a significant number of patients after treatment. This finding can be of importance for clinicians in relation to patient information concerning AEs possibly related to DAA treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MEG.0000000000001192DOI Listing
October 2018

Immune-escape mutations and stop-codons in HBsAg develop in a large proportion of patients with chronic HBV infection exposed to anti-HBV drugs in Europe.

BMC Infect Dis 2018 06 1;18(1):251. Epub 2018 Jun 1.

Virology Laboratory, Centre Hospitalier Régional et Université "Victor Segalen", Bordeaux, France.

Background: HBsAg immune-escape mutations can favor HBV-transmission also in vaccinated individuals, promote immunosuppression-driven HBV-reactivation, and increase fitness of drug-resistant strains. Stop-codons can enhance HBV oncogenic-properties. Furthermore, as a consequence of the overlapping structure of HBV genome, some immune-escape mutations or stop-codons in HBsAg can derive from drug-resistance mutations in RT. This study is aimed at gaining insight in prevalence and characteristics of immune-associated escape mutations, and stop-codons in HBsAg in chronically HBV-infected patients experiencing nucleos(t)ide analogues (NA) in Europe.

Methods: This study analyzed 828 chronically HBV-infected European patients exposed to ≥ 1 NA, with detectable HBV-DNA and with an available HBsAg-sequence. The immune-associated escape mutations and the NA-induced immune-escape mutations sI195M, sI196S, and sE164D (resulting from drug-resistance mutation rtM204 V, rtM204I, and rtV173L) were retrieved from literature and examined. Mutations were defined as an aminoacid substitution with respect to a genotype A or D reference sequence.

Results: At least one immune-associated escape mutation was detected in 22.1% of patients with rising temporal-trend. By multivariable-analysis, genotype-D correlated with higher selection of ≥ 1 immune-associated escape mutation (OR[95%CI]:2.20[1.32-3.67], P = 0.002). In genotype-D, the presence of ≥ 1 immune-associated escape mutations was significantly higher in drug-exposed patients with drug-resistant strains than with wild-type virus (29.5% vs 20.3% P = 0.012). Result confirmed by analysing drug-naïve patients (29.5% vs 21.2%, P = 0.032). Strong correlation was observed between sP120T and rtM204I/V (P < 0.001), and their co-presence determined an increased HBV-DNA. At least one NA-induced immune-escape mutation occurred in 28.6% of patients, and their selection correlated with genotype-A (OR[95%CI]:2.03[1.32-3.10],P = 0.001). Finally, stop-codons are present in 8.4% of patients also at HBsAg-positions 172 and 182, described to enhance viral oncogenic-properties.

Conclusions: Immune-escape mutations and stop-codons develop in a large fraction of NA-exposed patients from Europe. This may represent a potential threat for horizontal and vertical HBV transmission also to vaccinated persons, and fuel drug-resistance emergence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12879-018-3161-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5984771PMC
June 2018

Analytical performance of the Hologic Aptima HBV Quant Assay and the COBAS Ampliprep/COBAS TaqMan HBV test v2.0 for the quantification of HBV DNA in plasma samples.

J Clin Virol 2018 07 18;104:83-88. Epub 2018 May 18.

Department of Clinical Microbiology, Copenhagen University Hospital, Hvidovre, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.

Background: Quantification of HBV DNA is used for initiating and monitoring antiviral treatment. Analytical test performance consequently impacts treatment decisions.

Objectives: To compare the analytical performance of the Aptima HBV Quant Assay (Aptima) and the COBAS Ampliprep/COBAS TaqMan HBV Test v2.0 (CAPCTMv2) for the quantification of HBV DNA in plasma samples.

Study Design: The performance of the two tests was compared on 129 prospective plasma samples, and on 63 archived plasma samples of which 53 were genotyped. Linearity of the two assays was assessed on dilutions series of three clinical samples (Genotype B, C, and D).

Results: Bland-Altman analysis of 120 clinical samples, which quantified in both tests, showed an average quantification bias (Aptima - CAPCTMv2) of -0.19 Log IU/mL (SD: 0.33 Log IU/mL). A single sample quantified more than three standard deviations higher in Aptima than in CAPCTMv2. Only minor differences were observed between genotype A (N = 4; average difference -0.01 Log IU/mL), B (N = 8; -0.13 Log IU/mL), C (N = 8; -0.31 Log IU/mL), D (N = 25; -0.22 Log IU/mL), and E (N = 7; -0.03 Log IU/mL). Deming regression showed that the two tests were excellently correlated (slope of the regression line 1.03; 95% CI: 0.998-1.068). Linearity of the tests was evaluated on dilution series and showed an excellent correlation of the two tests. Both tests were precise with %CV less than 3% for HBV DNA ≥3 Log IU/mL.

Conclusions: The Aptima and CAPCTMv2 tests are highly correlated, and both tests are useful for monitoring patients chronically infected with HBV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcv.2018.05.007DOI Listing
July 2018

Direct acting antiviral treatment of chronic hepatitis C in Denmark: factors associated with and barriers to treatment initiation.

Scand J Gastroenterol 2018 Jun - Jul;53(7):849-856. Epub 2018 May 2.

a Department of Infectious Diseases , Copenhagen University Hospital , Hvidovre , Denmark.

Objectives: We describe factors associated with and barriers to initiation of Direct Acting Antiviral (DAA) treatment in patients with chronic hepatitis C, who fulfill national fibrosis treatment guidelines in Denmark.

Materials And Methods: In this nationwide cohort study, we included patients with chronic hepatitis C from The Danish Database for Hepatitis B and C (DANHEP) who fulfilled fibrosis treatment criteria. Factors associated with treatment initiation and treatment failure were determined by logistic regression analyses. Medical records were reviewed from patients who fulfilled fibrosis treatment criteria, but did not initiate DAA treatment to determine the cause.

Results: In 344 (49%) of 700 patients, who fulfilled treatment criteria, factors associated with DAA treatment initiation were transmission by other routes than injecting drug use odds ratio (OR) 2.13 (CI: 1.38-3.28), previous treatment failure OR 2.58 (CI: 1.84-3.61) and ALT above upper limit of normal OR 1.60 (CI: 1.18-2.17). The most frequent reasons for not starting treatment among 356 (51%) patients were non-adherence to medical appointments (n = 107/30%) and ongoing substance use (n = 61/17%). Treatment failure with viral relapse occurred in 19 (5.5%) patients, who were more likely to have failed previous treatment OR 4.53 (CI: 1.59-12.91).

Conclusions: In this nationwide cohort study, we found non-adherence to medical appointments and active substance use to be major obstacles for DAA treatment initiation. Our findings highlight the need for interventions that can overcome these barriers and increase the number of patients who can initiate and benefit from curative DAA treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00365521.2018.1467963DOI Listing
November 2018

Anti-müllerian hormone levels are reduced in women living with human immunodeficiency virus compared to control women: a case-control study from Copenhagen, Denmark.

J Virus Erad 2018 Apr 1;4(2):123-127. Epub 2018 Apr 1.

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Denmark.

Objectives: Anti-müllerian hormone (AMH) is a marker of ovarian reserve. The purpose of this study was to compare AMH in women living with HIV with an age-matched control group of HIV-uninfected women, and to identify possible variables associated with decreasing AMH levels in women living with HIV.

Methods: AMH was measured in frozen EDTA samples from 84 white women living with HIV, aged 20 -40 years, with fully suppressed HIV RNA viral loads for at least 6 months and no hepatitis B or C virus co-infection. All women living with HIV were age-matched with HIV-uninfected control women.

Results: Eighty-four women living with HIV and 252 control women were included. Median age for the women living with HIV was 33.5 years (interquartile range [IQR] 30.6-35.3), and 33.2 years (IQR 30.6-35.5) for the control women. A significant difference (=0.03) was found in the mean AMH levels for all age groups combined, which was 17.23 pmol/L (95% confidence interval [CI] 14.56-19.89) in the women living with HIV versus 21.65 pmol/L (95% CI 19.50-23.81) in the control women, although levels were within reference limits in both groups.Only increasing age was significantly associated with decreasing AMH levels and not CD4 cell count, AIDS prior to inclusion, antiretroviral treatment/lack of treatment or antiretroviral treatment regimen.

Conclusions: Well-treated, white women living with HIV in Denmark, have reduced AMH levels compared with age-matched control HIV-uninfected women. The only variable associated with decreasing AMH levels in women living with HIV was increasing age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892676PMC
April 2018
-->