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https://infmed.dk/hepatitis#fertilitetsbehandling_ved_hiv_og_hepatitis_(2018).pdf
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Guidelines 1 Hepatitis B (2018)
National guideline udarbejdet af en arbejdsgruppe nedsat af medlemmer fra Dansk Selskab for Infektionsmedicin og medlemmer fra Dansk Selskab for Gastroenterologi og Hepatologi. 2 Hepatitis C (2022)
National guideline udarbejdet af en arbejdsgruppe nedsat af medlemmer fra Dansk Selskab for Infektionsmedicin og medlemmer fra Dansk Selskab for Gastroenterologi og Hepatologi. 3 Stikuheld og anden blodeksposition (2020)
Revideret september 2020. Arbejdsgruppen bestod af Suzanne Lunding (formand), Peer Brehm Christensen, Christian Erikstrup, Terese L. Katzenstein, Henrik Krarup, Alex Lund Laursen, Birgitte Mørn og Nina Weis Links 1 EASL Clinical Practice Guidelines
2 Medicin.dk om behandling af hepatitis B
3 Medicin.dk om behandling af hepatitis C
4 Medicinrådets lægemiddelrekommandation for behandling af kronisk hepatitis C infektion
5 Dansk standard for rapportering af kronisk hepatitis B og C
6 Public health guidance on HIV, hepatitis B and C testing in the EU/EEA
Nye artikler 1 A fragment-based drug discovery developed on ciclopirox for inhibition of Hepatitis B virus core protein: An in silico study Alireza Mohebbi, Touba Ghorbanzadeh, Shabnam Naderifar, Fattaneh Khalaj, Fatemeh Sana Askari, Ali Salehnia Sammak PLoS One Infectious Diseases, 17.05.2023 Tilføjet 17.05.2023 by Alireza Mohebbi, Touba Ghorbanzadeh, Shabnam Naderifar, Fattaneh Khalaj, Fatemeh Sana Askari, Ali Salehnia Sammak The Hepatitis B virus (HBV) core protein is an attractive target for preventing capsid assembly and viral replication. Drug repurposing strategies have introduced several drugs targeting HBV core protein. This study used a fragment-based drug discovery (FBDD) approach to reconstruct a repurposed core protein inhibitor to some novel antiviral derivatives. Auto Core Fragment in silico Screening (ACFIS) server was used for deconstruction-reconstruction of Ciclopirox in complex with HBV core protein. The Ciclopirox derivatives were ranked based on their free energy of binding (ΔGB). A quantitative structure affinity relationship (QSAR) was established on the Ciclopirox derivatives. The model was validated by a Ciclopirox-property-matched decoy set. A principal component analysis (PCA) was also assessed to define the relationship of the predictive variable of the QSAR model. 24-derivatives with a ΔGB (-16.56±1.46 Kcal.mol-1) more than Ciclopirox was highlighted. A QSAR model with a predictive power of 88.99% (F-statistics = 9025.78, corrected df(25), Pr > F = 0.0001) was developed by four predictive descriptors (ATS1p, nCs, Hy, F08[C-C]). The model validation showed no predictive power for the decoy set (Q2 = 0). No significant correlation was observed between predictors. By directly attaching to the core protein carboxyl-terminal domain, Ciclopirox derivatives may be able to suppress HBV virus assembly and subsequent viral replication inhibition. Hydrophobic residue Phe23 is a critical amino acid in the ligand binding domain. These ligands share the same physicochemical properties that lead to the development of a robust QSAR mode. The same strategy may also be used for future drug discovery of viral inhibitors. Læs mere Tjek på PubMed2 Screening and Vaccination to Eradicate Hepatitis B Journal of the American Medical Association, 16.05.2023 Tilføjet 16.05.2023 This Viewpoint describes new recommendations from the CDC regarding universal screening of adults for hepatitis B virus infection. Læs mere Tjek på PubMed3 Occult hepatitis B virus infection is associated with Chinese patients’ liver fibrosis Journal of Infectious Diseases, 13.05.2023 Tilføjet 13.05.2023 AbstractBackgroundThe impact of occult HBV infection with HBsAg-/HBV DNA+ (OBI) on severity of liver fibrosis remains unclear.MethodsA total of 1772 HBsAg negative but anti-HBc positive subjects stratified between OBI and non-OBI were selected for long-term carriage leading to at least two of four liver fibrosis indexes elevated: hyaluronic acid (HA), laminin (LN), type III procollagen peptide (PCIII) or type IV collagen (CIV) tested in a Chinese hospital. Patients were tested for serum viral load, and HBV markers and histopathological changes in liver biopsies.ResultsOBI was identified in 148 liver fibrosis patients (8.4%), who had significantly higher levels of HA, LN, PCIII and CIV than 1624 fibrotic patients without OBI (P Læs mere Tjek på PubMed4 High Prevalence of Occult Hepatitis B Virus Infection among Iranian Hemodialysis Patients American Journal of Tropical Medicine and Hygiene, 3.05.2023 Tilføjet 3.05.2023 Journal Name: The American Journal of Tropical Medicine and Hygiene Volume: 108 Issue: 5 Pages: 1017-1024 Læs mere Tjek på PubMed5 Residual risk of mother-to-child transmission of HBV despite timely Hepatitis B vaccination: a major challenge to eliminate hepatitis B infection in Cambodia BMC Infectious Diseases, 27.04.2023 Tilføjet 27.04.2023 Abstract Background In countries with intermediate or high hepatitis B virus (HBV) endemicity, mother-to-child transmission (MTCT) represents the main route of chronic HBV infection. There is a paucity of information on HBV MTCT in Cambodia. This study aimed to investigate the prevalence of HBV infection among pregnant women and its MTCT rate in Siem Reap, Cambodia. Methods This longitudinal study included two parts, study-1 to screen HBsAg among pregnant women and study-2 to follow up babies of all HBsAg-positive and one-fourth of HBsAg-negative mothers at their delivery and six-month post-partum. Serum or dried blood spot (DBS) samples were collected to examine HBV sero-markers by chemiluminescent enzyme immunoassay (CLEIA), and molecular analyses were performed on HBsAg-positive samples. Structured questionnaires and medical records were used to examine the risk factors for HBV infection. MTCT rate was calculated by HBsAg positivity of 6-month-old babies born to HBsAg-positive mothers and ascertained by the homology of HBV genomes in mother–child pair at 6-month-old. Results A total of 1,565 pregnant women were screened, and HBsAg prevalence was 4.28% (67/1565). HBeAg positivity was 41.8% and was significantly associated with high viral load (p Læs mere Tjek på PubMed6 Nomogram for evaluating obvious liver inflammation in treatment-naïve HBeAg positive chronic hepatitis B virus infection patients with normal ALT Lu Zhang, Liu Yang, Yuanjiao Gao, Xiaoyue Bi, Yanjie Lin, Wen Deng, Tingting Jiang, Yao Lu, Hongxiao Hao, Gang Wan, Wei Yi, Yao Xie, Minghui Li Virulence, 24.04.2023 Tilføjet 24.04.2023 7 Hepatitis B core-related antigen serum levels may be a predictor of acute flare of chronic hepatitis B among pregnant women in the immune-tolerant phase of chronic HBV infection after short-course antiviral therapy Ruyu Liu, Liu Yang, Tingting Jiang, Yao Lu, Lu Zhang, Ge Shen, Shuling Wu, Min Chang, Hongxiao Hao, Leiping Hu, Yuanjiao Gao, Mengjiao Xu, Xiaoxue Chen, Wei Yi, Minghui Li, Yao Xie Virulence, 24.04.2023 Tilføjet 24.04.2023 8 Mitochondrial HIGD1A inhibits hepatitis B virus transcription and replication through the cellular PNKD‐NF‐κB‐NR2F1 nexus Zhanglian Xie, Sheng Shen, Kuiyuan Huang, Weibin Wang, Ziying Liu, Haixing Zhang, Mengji Lu, Jian Sun, Jinlin Hou, Hongyan Liu, Haitao Guo, Xiaoyong Zhang Journal of Medical Virology, 22.04.2023 Tilføjet 22.04.2023 9 Hepatitis B and C in individuals with a history of antipsychotic medication use: A population-based evaluation Amnah Awan, Sharara Shakik, Hailey R. Banack, David N. Fisman, Alison E. Simmons PLoS One Infectious Diseases, 14.04.2023 Tilføjet 15.04.2023 by Amnah Awan, Sharara Shakik, Hailey R. Banack, David N. Fisman, Alison E. Simmons Background A better understanding of links between mental illness and risk of bloodborne infectious disease could inform preventive and therapeutic strategies in individuals with mental illness. Methods We performed a cross-sectional study using the National Health and Nutrition Examination Survey (NHANES) to estimate the seroprevalence of hepatitis B and C in individuals with and without a prior prescription for antipsychotic medications, and to determine whether differences in seroprevalence could be explained by differential distribution in known infection risk factors. Multivariable logistic regression models were used to examine the association between receipt of antipsychotic medication and HBV and HCV seropositivity. Results Those who had HBV core antibody had 1.64 (95% CI: 0.89, 3.02) times the odds and those with HCV antibody (anti-HCV) had 3.48 (95% CI: 1.71, 7.09) times the odds of having a prescription for at least one antipsychotic medication compared to those who did not have HBV core antibody or HCV antibody, respectively. While prior antipsychotic receipt was a potent risk marker for HCV seropositivity, risk was explained by adjusting for known bloodborne infection risk factors (adjusted ORs 1.01 [95% CI: 0.50, 2.02] and 1.38 [95% CI: 0.44, 4.36] for HBV and HCV, respectively). Conclusions Prior receipt of antipsychotic medications is a strong predictor of HCV (and to a lesser extent HBV) seropositivity. Treatment with antipsychotic medications should be considered as additional risk markers for individuals who may benefit from targeted prevention, screening, and harm reduction interventions for HCV. Læs mere Tjek på PubMed10 An RNA-based system to study hepatitis B virus replication and evaluate antivirals Yingpu Yu, William M. Schneider, Maximilian A. Kass, Eleftherios Michailidis, Ashley Acevedo, Ana L. Pamplona Mosimann, Juliano Bordignon, Alexander Koenig, Christine M. Livingston, Hardeep van Gijzel, Yi Ni, Pradeep M. Ambrose, Catherine A. Freije, Mengyin Zhang, Chenhui Zou, Mohammad Kabbani, Corrine Quirk, Cyprien Jahan, Xianfang Wu, Stephan Urban, Shihyun You, Amir Shlomai, Ype P. de Jong, Charles M. Rice Science Advances, 12.04.2023 Tilføjet 12.04.2023 11 Immunogenicity and Safety of Hepatitis B vaccine with a Toll-like Receptor 9 Agonist Adjuvant (HEPLISAV-B) in HBV Vaccine-naive People with HIV Clinical Infectious Diseases, 6.04.2023 Tilføjet 6.04.2023 AbstractIn this international, multicenter open-label study (ACTG A5379) of HepB-CpG vaccine in people with HIV without prior Hepatitis B Virus (HBV) vaccination, all 68 participants achieved HBV seroprotective titers after the 3-dose series in the primary analysis. No unexpected safety issues were observed. Læs mere Tjek på PubMed12 The high burden of comorbidities in Aboriginal and Torres Strait Islander Australians living with chronic hepatitis B in Far North Queensland, Australia, and the implications for patient management Jordan Riddell, Allison Hempenstall, Yoko Nakata, Sandra Gregson, Richard Hayes, Simon Smith, Marlow Coates, Lizzie Charlie, Christine Perrett, Victoria Newie, Tomi Newie, Sharna Radlof, Josh Hanson PLoS One Infectious Diseases, 6.04.2023 Tilføjet 7.04.2023 by Jordan Riddell, Allison Hempenstall, Yoko Nakata, Sandra Gregson, Richard Hayes, Simon Smith, Marlow Coates, Lizzie Charlie, Christine Perrett, Victoria Newie, Tomi Newie, Sharna Radlof, Josh Hanson Background Aboriginal and Torres Strait Islander Australians living with chronic hepatitis B virus (HBV) infection have a significant burden of hepatocellular carcinoma (HCC). The prevalence of comorbidities that increase the risk of HCC in this population is incompletely defined. Methods This cross-sectional study was performed in remote tropical Queensland, Australia in January 2021. All individuals living with chronic HBV in the region were identified; the prevalence of relevant comorbidities was determined by reviewing medical records. Results All 236 individuals in the cohort identified as Aboriginal and Torres Strait Islander Australians; their median (interquartile range (IQR)) age was 48 (40–62) years; 120/236 (50.9%) were female. Of the 194/236 (82.2%) engaged in HBV care, 61 (31.4%) met criteria for HBV therapy and 38 (62.2%) were receiving it. However, 142/236 (60.2%) were obese, 73/236 (30.9%) were current smokers and 57/236 (24.2%) were drinking alcohol hazardously; 70/236 (29.7%) had ≥2 of these additional risk factors for HCC, only 43/236 (18.2%) had none. Among the 19 patients with confirmed cirrhosis, 9 (47%) were obese, 8 (42%) were currently—or had a history of—drinking alcohol hazardously and 5 (26.3%) were current smokers. Patients also had a median (IQR) of 3 (2–4) cardiovascular risk factors (cigarette smoking, hypertension, impaired glucose tolerance, dyslipidaemia, renal impairment/proteinuria). Only 9/236 (3.8%) did not have one of these 5 comorbidities. Conclusions Aboriginal and Torres Strait Islander Australians living with chronic HBV in this region of remote Australia have a high engagement with HBV care and the majority of individuals eligible for antiviral therapy are receiving it. However, a significant comorbidity burden increases their risk of cirrhosis, HCC, and premature death. It is essential to integrate chronic HBV care with management of these comorbidities—rather than focusing on HBV alone—to achieve optimal health outcomes. Læs mere Tjek på PubMed13 Impact of maternal hepatitis B carrier status on congenital abnormalities: a systematic review and meta-analysis BMJ Open, 28.03.2023 Tilføjet 28.03.2023 ObjectivesThis study aims to explore whether maternal hepatitis B carrier status is associated with an increased risk of congenital abnormalities.DesignA systematic review and meta-analysis of observational studies.Data sourcesPubMed, Embase (Ovid), Scopus, the China National Knowledge Infrastructure (CNKI) and the Wanfang databases.Study selectionFive databases were searched systematically from inception to 7 September 2021. Cohort and case–control studies that investigated the association between maternal hepatitis B virus (HBV) infection and congenital abnormalities were included. This study was conducted according to MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines.Data extraction and synthesisTwo reviewers independently collected data, as well as assessed risk of bias by using Newcastle–Ottawa Scale. We pooled crude relative risk (cRR) and adjusted OR (aOR) by DerSimonian-Laird random-effects model. Heterogeneity was explored by I2 statistics, Cochran’s Q test. Several subgroup analyses and sensitivity analyses were performed.ResultsIn total, 14 studies involving 16 205 pregnant women exposed to HBV were included. The pooled cRR of 1.15 (95% CI: 0.92 to 1.45; 14 studies included) showed a marginal but not significant association between maternal HBV-carrier status and congenital abnormalities. However, the pooled aOR of 1.40 (95% CI: 1.01 to 1.93; 8 studies included) indicated that pregnant women with HBV infection might be associated with a higher risk of congenital abnormalities. Subgroup analyses of adjusted data showed a higher pooling cRR or aOR on high prevalence HBV infection populations, as well as studies from Asia and Oceania.ConclusionsMaternal hepatitis B carrier status might be at potential risk for congenital abnormalities. The existing evidence was not sufficient to draw a firm conclusion. Additional studies may be warranted to confirm the association.PROSPERO registration numberCRD42020205459. Læs mere Tjek på PubMed14 Humoral responses after primary and booster SARS‐CoV‐2 inactivated vaccination in patients with chronic hepatitis B virus infection: a longitudinal observational study Journal of Medical Virology, 22.03.2023 Tilføjet 23.03.2023 15 Efficacy and Safety of Bepirovirsen in Hepatitis B New England Journal of Medicine, 22.03.2023 Tilføjet 23.03.2023 New England Journal of Medicine, Volume 388, Issue 12, Page 1146-1148, March 2023. Læs mere Tjek på PubMed16 Assessment of a primary care e-support package of automated case finding, simplified treatment algorithm and decision support to increase hepatitis B treatment uptake in primary care clinics in Australia (SIMPLY-B Study): protocol for a pilot evaluation BMJ Open, 16.03.2023 Tilføjet 17.03.2023 IntroductionDespite the availability of effective, subsidised hepatitis B treatment, linkage to care and treatment rates remain very low globally. In Australia, specially trained primary care physicians (general practitioner, GPs) can prescribe hepatitis B treatment, however, most hepatitis B care occurs in specialist clinics. Increasing hepatitis B management by GPs in primary care clinics is essential to achieve national hepatitis B linkage to care and treatment targets by 2030.This pilot study determines the feasibility, acceptability and effectiveness of Simply B, a novel GP hepatitis B e-support package designed to increase hepatitis B management by GPs in primary care clinics.Methods and analysisThis study will be conducted in three parts:Part A: A prospective open-label pilot intervention study, comparing the proportion of people with hepatitis B who are managed by their GP in primary care clinics before, 12 months and 24 months after implementation of the Simply B electronic hepatitis B support package.Part B: A nested qualitative health services feasibility study using semistructured interviews and thematic analysisPart C: Cost-effectiveness analysis.Ethics and disseminationThis study has received ethics approval by St Vincent’s Hospital. Data management and analysis will be centralised through the Department of Gastroenterology, St Vincent’s Hospital.Trial registration numberNCT05614466. Læs mere Tjek på PubMed17 Prevalence of HIV, syphilis, and hepatitis B and C virus infections in pregnant women: A systematic review and meta-analysis Clinical Microbiology and Infection, 12.03.2023 Tilføjet 13.03.2023 At the 74th World Health Assembly, the World Health Organization (WHO) issued a strategy for the prevention and control of several major infectious diseases. To achieve the WHO-initiated targets for these infectious diseases, the elimination of mother-to-child transmission is essential. To date, a systematic review of the global and regional prevalence of infections with relevant mother-to-child transmission and outside the spectrum of congenital infections is lacking. Læs mere Tjek på PubMed18 Seroprevalence of hepatitis B virus surface antigen (HBsAg) in Egypt (2000–2022): a systematic review with meta-analysis BMC Infectious Diseases, 10.03.2023 Tilføjet 10.03.2023 Abstract Background Hepatitis B infection seriously threatens global public health, especially in developing nations. Despite several investigations on HBV incidence, the national pooled prevalence remains unknown, particularly in populations at-risk at whom interventions should be primarily aimed. Methods A comprehensive literature search of the following databases: Medline [PubMed], Scopus, Google Scholar, and Web of Science was conducted following the PRISMA guidelines. I-squared and Cochran's Q were used to measure the heterogeneity between the studies. Publications that matched the following were included: Primary studies published in Egypt from 2000 to 2022 reported HBV prevalence based on HBsAg. We excluded any studies that were not performed on Egyptians or that were performed on patients suspected of acute viral hepatitis or studies focusing on occult hepatitis or vaccination evaluation studies, or national surveys. Results The systematic review included 68 eligible studies reporting a total of 82 incidences of HBV infection based on hepatitis B surface antigen with a total sample size of 862,037. The pooled national prevalence among studies was estimated to be 3.67% [95% CI; 3: 4.39]. Children under 20 with a history of HBV vaccination during infancy had the lowest prevalence of 0.69%. The pooled prevalence of HBV infection among pregnant women, blood donors, and healthcare workers was 2.95%, 1.8%, and 1.1%, respectively. While patients with hemolytic anemia and hemodialysis patients, patients with malignancies, HCC patients, and chronic liver disease patients had the highest prevalences at 6.34%, 25.5%, 18.6%, and 34%, respectively. Studies reporting HBV prevalence in urban settings compared to rural settings revealed a similar HBV prevalence of 2.43% and 2.15%, respectively. Studies comparing HBV prevalence in males and females revealed a higher prevalence among males (3.75%) than females (2.2%). Conclusion In Egypt, hepatitis B infection is a significant public health issue. The blocking of mother-to-infant hepatitis B transmission, the scaling up of the scope of the existing vaccination program, and implementing new strategies, including screen-and-treat, may reduce the prevalence of the disease. Læs mere Tjek på PubMed19 Is nonalcoholic fatty liver disease a predictor of treatment response in chronic hepatitis B? Journal of Medical Virology, 10.03.2023 Tilføjet 11.03.2023 20 Safety and efficacy of double plasma molecular adsorption system with sequential low‐volume plasma exchange in intermediate‐stage hepatitis B virus‐related acute‐on‐chronic liver failure Journal of Medical Virology, 10.03.2023 Tilføjet 11.03.2023 |
Værktøj 1 Child-Pugh score (MDCalc)
2 Hep Drug Interactions
3 The Polaris Observatory (epidemiologi og modellering)
Referencer 1 No detectable resistance to tenofovir disoproxil fumarate in HBeAg+ and HBeAg- patients with chronic hepatitis B after 8 years of treatment. J Viral Hepat 2017; 24(1):68-74
Liu Y, Corsa AC, Buti M, Cathcart AL, Flaherty JF, Miller MD, Kitrinos KM, Marcellin P, Gane EJ
A major hurdle in the long-term treatment of chronic hepatitis B (CHB) patients is to maintain viral suppression in the absence of drug resistance. To date, no evidence of resistance to tenofovir disoproxil fumarate (TDF) has been observed. A cumulative evaluation of CHB patients who qualified for resistance surveillance over 8 years of TDF treatment was conducted. Patients in studies GS-US-174-0102 (HBeAg-) and GS-US-174-0103 (HBeAg+) were randomized 2:1 to receive TDF or adefovir dipivoxil (ADV) for 48 weeks followed by open-label TDF through year 8. Population sequencing of HBV pol/RT was attempted for all TDF-treated patients at baseline and, annually if viremic, at discontinuation, or with addition of emtricitabine. Overall, 88/641 (13.7%) patients qualified for sequence analysis at one or more time points. The percentage of patients qualifying for sequence analysis declined over time, from 9 to 11% in years 1-2 to <4% over years 3-8. Forty-one episodes of virologic breakthrough (VB) occurred throughout the study, with most (n=29, 70%) associated with nonadherence to study medication. Fifty-nine per cent of VB patients with an opportunity to resuppress HBV achieved HBV DNA resuppression. A minority of patients who qualified for sequencing had polymorphic (41/165, 24.8%) or conserved (17/165, 10.3%) site changes in pol/RT, with six patients developing lamivudine and/or ADV resistance-associated mutations. No accumulation of conserved site changes was detected. The long-term treatment of CHB with TDF monotherapy maintains effective suppression of HBV DNA through 8 years, with no evidence of TDF resistance or accumulation of conserved site changes. PMID: 276583432 Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med 2015; 373(27):2608-17
Foster GR, Afdhal N, Roberts SK, Bräu N, Gane EJ, Pianko S, Lawitz E, Thompson A, Shiffman ML, Cooper C, Towner WJ, Conway B, Ruane P, Bourlière M, Asselah T, Berg T, Zeuzem S, Rosenberg W, Agarwal K, Stedman CA, Mo H, Dvory-Sobol H, Han L, Wang J, McNally J, Osinusi A, Brainard DM, McHutchison JG, Mazzotta F, Tran TT, Gordon SC, Patel K, Reau N, Mangia A, Sulkowski M
In phase 2 trials, treatment with the combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir resulted in high rates of sustained virologic response in patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3. PMID: 265752583 Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med 2015; 373(27):2599-607
Feld JJ, Jacobson IM, Hézode C, Asselah T, Ruane PJ, Gruener N, Abergel A, Mangia A, Lai CL, Chan HL, Mazzotta F, Moreno C, Yoshida E, Shafran SD, Towner WJ, Tran TT, McNally J, Osinusi A, Svarovskaia E, Zhu Y, Brainard DM, McHutchison JG, Agarwal K, Zeuzem S
A simple treatment regimen that is effective in a broad range of patients who are chronically infected with the hepatitis C virus (HCV) remains an unmet medical need. PMID: 265710664 Extrahepatic morbidity and mortality of chronic hepatitis C. Gastroenterology 2015; 149(6):1345-60
Negro F, Forton D, Craxì A, Sulkowski MS, Feld JJ, Manns MP
Chronic hepatitis C virus (HCV) infection is associated with several extrahepatic manifestations. Patients with HCV may develop mixed cryoglobulinemia and its sequelae, ranging from cutaneous and visceral vasculitis to glomerulonephritis and B-cell non-Hodgkin lymphoma. HCV-infected patients have increased rates of insulin resistance, diabetes, and atherosclerosis, which may lead to increased cardiovascular morbidity and mortality. Neurological manifestations of HCV infection include fatigue and cognitive impairment. The mechanisms causing the extrahepatic effects of HCV infection are likely multifactorial and may include endocrine effects, HCV replication in extrahepatic cells, or a heightened immune reaction with systemic effects. Successful eradication of HCV with interferon alfa and ribavirin was shown to improve some of these extrahepatic effects; sustained virological response is associated with resolution of complications of cryoglobulinemia, reduced levels of insulin resistance, reduced incidence of diabetes and stroke, and improved fatigue and cognitive functioning. The availability of new interferon-free, well-tolerated anti-HCV treatment regimens is broadening the spectrum of patients available for therapy, including those in whom interferon was contraindicated, and will likely result in greater improvements in the extrahepatic manifestations of HCV. If these regimens are shown to confer significant benefit in the metabolic, cardiovascular, or neuropsychiatric conditions associated with HCV infection, extrahepatic manifestations of HCV may become a major indication for treatment even in the absence of liver disease. PMID: 263190135 Ledipasvir and sofosbuvir for hepatitis C genotype 4: a proof-of-concept, single-centre, open-label phase 2a cohort study. Lancet Infect Dis 2015; 15(9):1049-1054
Kohli A, Kapoor R, Sims Z, Nelson A, Sidharthan S, Lam B, Silk R, Kotb C, Gross C, Teferi G, Sugarman K, Pang PS, Osinusi A, Polis MA, Rustgi V, Masur H, Kottilil S
Worldwide, although predominantly in low-income countries in the Middle East and Africa, up to 13% of hepatitis C virus (HCV) infections are caused by HCV genotype 4. For patients with HCV genotype 1, the combination of ledipasvir and sofosbuvir has been shown to cure high proportions of patients with excellent tolerability, but this regimen has not been assessed for the treatment of HCV genotype 4. We assessed the efficacy, safety, and tolerability of 12 weeks of combination therapy with ledipasvir and sofosbuvir for patients with chronic HCV genotype 4 infections. PMID: 261870316 Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial. Ann Intern Med 2015; 163(1):1-13
Zeuzem S, Ghalib R, Reddy KR, Pockros PJ, Ben Ari Z, Zhao Y, Brown DD, Wan S, DiNubile MJ, Nguyen BY, Robertson MN, Wahl J, Barr E, Butterton JR
Novel interferon- and ribavirin-free regimens are needed to treat hepatitis C virus (HCV) infection. PMID: 259093567 Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent. J Hepatol 2015; 63(3):564-72
Forns X, Gordon SC, Zuckerman E, Lawitz E, Calleja JL, Hofer H, Gilbert C, Palcza J, Howe AY, DiNubile MJ, Robertson MN, Wahl J, Barr E, Buti M
The Phase-2 C-SALVAGE study evaluated an investigational interferon-free combination of grazoprevir (a NS3/4A protease inhibitor) and elbasvir (a NS5A inhibitor) with ribavirin for patients with chronic HCV genotype-1 infection who had failed licensed DAA-containing therapy. PMID: 258954288 Ombitasvir plus paritaprevir plus ritonavir with or without ribavirin in treatment-naive and treatment-experienced patients with genotype 4 chronic hepatitis C virus infection (PEARL-I): a randomised, open-label trial. Lancet 2015; 385(9986):2502-9
Hézode C, Asselah T, Reddy KR, Hassanein T, Berenguer M, Fleischer-Stepniewska K, Marcellin P, Hall C, Schnell G, Pilot-Matias T, Mobashery N, Redman R, Vilchez RA, Pol S
Hepatitis C virus (HCV) genotype 4 accounts for about 13% of global HCV infections. Because interferon-containing treatments for genotype 4 infection have low efficacy and poor tolerability, an unmet need exists for effective all-oral regimens. We examined the efficacy and safety of an all-oral interferon-free regimen of ombitasvir, an NS5A inhibitor, and paritaprevir (ABT-450), an NS3/4A protease inhibitor dosed with ritonavir (ombitasvir plus paritaprevir plus ritonavir), given with or without ribavirin. PMID: 258378299 Ledipasvir-sofosbuvir with or without ribavirin to treat patients with HCV genotype 1 infection and cirrhosis non-responsive to previous protease-inhibitor therapy: a randomised, double-blind, phase 2 trial (SIRIUS). Lancet Infect Dis 2015; 15(4):397-404
Bourlière M, Bronowicki JP, de Ledinghen V, Hézode C, Zoulim F, Mathurin P, Tran A, Larrey DG, Ratziu V, Alric L, Hyland RH, Jiang D, Doehle B, Pang PS, Symonds WT, Subramanian GM, McHutchison JG, Marcellin P, Habersetzer F, Guyader D, Grangé JD, Loustaud-Ratti V, Serfaty L, Metivier S, Leroy V, Abergel A, Pol S
Patients with cirrhosis resulting from chronic hepatitis C virus (HCV) infection are at risk of life-threatening complications, but consistently achieve lower sustained virological response (SVR) than patients without cirrhosis, especially if treatment has previously failed. We assessed the efficacy and safety of the NS5A inhibitor ledipasvir and the nucleotide polymerase inhibitor sofosbuvir, with and without ribavirin. PMID: 2577375710 Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study. Lancet 2014; 384(9956):1756-65
Lawitz E, Sulkowski MS, Ghalib R, Rodriguez-Torres M, Younossi ZM, Corregidor A, DeJesus E, Pearlman B, Rabinovitz M, Gitlin N, Lim JK, Pockros PJ, Scott JD, Fevery B, Lambrecht T, Ouwerkerk-Mahadevan S, Callewaert K, Symonds WT, Picchio G, Lindsay KL, Beumont M, Jacobson IM
Interferon-free regimens are needed to treat hepatitis C virus (HCV) infections. We investigated the efficacy of combined simeprevir and sofosbuvir. PMID: 2507830911 Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med 2014; 370(16):1483-93
Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E, Nahass R, Ghalib R, Gitlin N, Herring R, Lalezari J, Younes ZH, Pockros PJ, Di Bisceglie AM, Arora S, Subramanian GM, Zhu Y, Dvory-Sobol H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Sulkowski M, Kwo P
Effective treatment for hepatitis C virus (HCV) genotype 1 infection in patients who have not had a sustained virologic response to prior interferon-based therapy represents an unmet medical need. PMID: 2472523812 Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med 2014; 370(17):1604-14
Zeuzem S, Jacobson IM, Baykal T, Marinho RT, Poordad F, Bourlière M, Sulkowski MS, Wedemeyer H, Tam E, Desmond P, Jensen DM, Di Bisceglie AM, Varunok P, Hassanein T, Xiong J, Pilot-Matias T, DaSilva-Tillmann B, Larsen L, Podsadecki T, Bernstein B
In this phase 3 trial we evaluated the efficacy and safety of the interferon-free combination of ABT-450 with ritonavir (ABT-450/r), ombitasvir (also known as ABT-267), dasabuvir (also known as ABT-333), and ribavirin for the retreatment of HCV in patients who were previously treated with peginterferon-ribavirin. PMID: 2472067913 Evolution of noninvasive tests of liver fibrosis is associated with prognosis in patients with chronic hepatitis C. Hepatology 2014; 60(1):65-76
Vergniol J, Boursier J, Coutzac C, Bertrais S, Foucher J, Angel C, Chermak F, Hubert IF, Merrouche W, Oberti F, de Lédinghen V, Calès P
No data are available about the prediction of long-term survival using repeated noninvasive tests of liver fibrosis in chronic hepatitis C (CHC). We aimed to assess the prognostic value of 3-year liver stiffness measurement (LSM), aspartate aminotransferase to platelet ratio index (APRI), and fibrosis 4 (FIB-4) evolution in CHC. CHC patients with two LSM (1,000-1,500 days interval) were prospectively included. Blood fibrosis tests APRI and FIB-4 were calculated the day of baseline (bLSM) and follow-up (fLSM) LSM. Evolution of fibrosis tests was expressed as delta: (follow-up-baseline results)/duration. Date and cause of death were recorded during follow-up that started the day of fLSM. In all, 1,025 patients were included. Median follow-up after fLSM was 38.0 months (interquartile range [IQR]: 27.7-46.1) during which 35 patients died (14 liver-related death) and seven had liver transplantation. Prognostic accuracy (Harrell C-index) of multivariate models including baseline and delta results was not significantly different between LSM and FIB-4 (P ≥ 0.24), whereas FIB-4 provided more accurate prognostic models than APRI (P = 0.03). By multivariate analysis including LSM variables, overall survival was independently predicted by bLSM, delta (dLSM), and sustained virological response (SVR). Prognosis was excellent in patients having bLSM <7 kPa, SVR, or no increase (<1 kPa/year) in 7-14 kPa bLSM. Prognosis was significantly impaired in patients with an increase (≥ 1 kPa/year) in 7-14 kPa bLSM, or decrease (≤ 0 kPa/year) in ≥ 14 kPa bLSM (P = 0.949 between these two groups). Patients with an increase (>0 kPa/year) in ≥ 14 kPa bLSM had the worst prognosis. Baseline and delta FIB-4 also identified patient subgroups with significantly different prognosis. PMID: 2451932814 Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med 2014; 370(3):211-21
Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein T, Jacobson I, Lawitz E, Lok AS, Hinestrosa F, Thuluvath PJ, Schwartz H, Nelson DR, Everson GT, Eley T, Wind-Rotolo M, Huang SP, Gao M, Hernandez D, McPhee F, Sherman D, Hindes R, Symonds W, Pasquinelli C, Grasela DM
All-oral combination therapy is desirable for patients with chronic hepatitis C virus (HCV) infection. We evaluated daclatasvir (an HCV NS5A replication complex inhibitor) plus sofosbuvir (a nucleotide analogue HCV NS5B polymerase inhibitor) in patients infected with HCV genotype 1, 2, or 3. PMID: 2442846715 Delayed versus immediate treatment for patients with acute hepatitis C: a randomised controlled non-inferiority trial. Lancet Infect Dis 2013; 13(6):497-506
Deterding K, Grüner N, Buggisch P, Wiegand J, Galle PR, Spengler U, Hinrichsen H, Berg T, Potthoff A, Malek N, Großhennig A, Koch A, Diepolder H, Lüth S, Feyerabend S, Jung MC, Rogalska-Taranta M, Schlaphoff V, Cornberg M, Manns MP, Wedemeyer H
Early treatment of acute hepatitis C virus (HCV) infection with interferon alfa monotherapy is very effective, with cure rates of greater than 85%. However, spontaneous clearance of HCV occurs in 10-50% of cases. We aimed to assess an alternative treatment strategy of delayed antiviral therapy in patients who do not eliminate the virus spontaneously compared with immediate treatment. PMID: 2352367416 Improvement of neurocognitive function in responders to an antiviral therapy for chronic hepatitis C. Hepatology 2013; 58(2):497-504
Kraus MR, Schäfer A, Teuber G, Porst H, Sprinzl K, Wollschläger S, Keicher C, Scheurlen M
Earlier studies have suggested neurocognitive impairment in patients with chronic hepatitis C virus (HCV) infection even before liver cirrhosis has developed. Since these deficits might be reversible after successful antiviral therapy, we analyzed the long-term course of neurocognitive parameters in HCV patients with and without successful virus elimination by an interferon-based antiviral treatment. In a multicenter study including 168 HCV patients receiving antiviral therapy (peginterferon alpha-2b and ribavirin) we performed a long-term follow-up of neurocognitive performance before and after treatment. Neurocognitive function was psychometrically assessed using the computer-aided TAP (Test Battery of Attentional Performance). When tested at least 12 months after termination of antiviral treatment, patients with sustained virologic response (SVR) had improved significantly as compared to their pretreatment performance in three of five TAP subtasks (vigilance, P < 0.001; shared attention: optical task, P < 0.001; working memory, P < 0.001). Patients who failed to eradicate the virus, however, showed no significant long-term changes in neurocognitive performance in all five subtasks assessed (0.194 < P < 0.804). In the posttreatment evaluation, neurocognitive function was significantly better in responders to the antiviral therapy as compared to nonresponders. PMID: 2330005317 Hepatitis C prevalence in Denmark -an estimate based on multiple national registers. BMC Infect Dis 2012; 12:178
Christensen PB, Hay G, Jepsen P, Omland LH, Just SA, Krarup HB, Weis N, Obel N, Cowan S
A national survey for chronic hepatitis C has not been performed in Denmark and the prevalence is unknown. Our aim was to estimate the prevalence of chronic hepatitis C from public registers and the proportion of these patients who received specialized healthcare. PMID: 2286692518 Acute hepatitis C in HIV-infected men who have sex with men: an emerging sexually transmitted infection. AIDS 2010; 24(12):1799-812
van de Laar TJ, Matthews GV, Prins M, Danta M
Since 2000 outbreaks of acute hepatitis C virus (HCV) among HIV-positive men who have sex with men (MSM) who denied injecting drug use have been reported from Europe, the United States, Canada and Australia. Given the burden of liver disease, in particular HCV, on the morbidity and mortality in HIV patients in the era of combination antiretroviral therapy, the rapid and significant rise in the incidence of HCV in the HIV-infected MSM population in high-income countries is alarming. This relates to a significant change in the epidemiology of HCV that has occurred, with HCV emerging as a sexually transmitted infection within this population. Work to date suggests that this permucosal HCV transmission results from high-risk sexual and noninjecting drug use behaviours, reopening the discussion on the importance of sexual transmission. Given this occurs almost exclusively in HIV-infected MSM, HIV probably has a critical role mediated either through behavioural and/or biological factors. Finally, the management of acute HCV in HIV infection is complicated by concomitant HIV infection and combination antiretroviral therapy. This review will synthesize the most recent epidemiological, immunological and management issues that have emerged as a result of the epidemic of acute HCV among HIV-infected MSM. PMID: 2060185419 Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med 2008; 359(23):2442-55
Marcellin P, Heathcote EJ, Buti M, Gane E, de Man RA, Krastev Z, Germanidis G, Lee SS, Flisiak R, Kaita K, Manns M, Kotzev I, Tchernev K, Buggisch P, Weilert F, Kurdas OO, Shiffman ML, Trinh H, Washington MK, Sorbel J, Anderson J, Snow-Lampart A, Mondou E, Quinn J, Rousseau F
Tenofovir disoproxil fumarate (DF) is a nucleotide analogue and a potent inhibitor of human immunodeficiency virus type 1 reverse transcriptase and hepatitis B virus (HBV) polymerase. PMID: 1905212620 Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology 2008; 134(6):1752-63
El-Serag HB, Marrero JA, Rudolph L, Reddy KR
The diagnosis and treatment of hepatocellular carcinoma (HCC) have witnessed major changes over the past decade. Until the early 1990s, HCC was a relatively rare malignancy, typically diagnosed at an advanced stage in a symptomatic patient, and there were no known effective palliative or therapeutic options. However, the rising incidence of HCC in several regions around the world coupled with emerging evidence for efficacy of screening in high-risk patients, liver transplantation as a curative option in select patients, ability to make definitive diagnosis using high-resolution imaging of the liver, less dependency on obtaining tissue diagnosis, and proven efficacy of transarterial chemoembolization and sorafenib as palliative therapy have improved the outlook for HCC patients. In this article, we present a summary of the most recent information on screening, diagnosis, staging, and different treatment modalities of HCC, as well as our recommended management approach. PMID: 1847155221 The HBV drug entecavir - effects on HIV-1 replication and resistance. N Engl J Med 2007; 356(25):2614-21
McMahon MA, Jilek BL, Brennan TP, Shen L, Zhou Y, Wind-Rotolo M, Xing S, Bhat S, Hale B, Hegarty R, Chong CR, Liu JO, Siliciano RF, Thio CL
Entecavir, a drug approved by the Food and Drug Administration for the treatment of chronic hepatitis B virus (HBV) infection, is not believed to inhibit replication of human immunodeficiency virus type 1 (HIV-1) at clinically relevant doses. We observed that entecavir led to a consistent 1-log(10) decrease in HIV-1 RNA in three persons with HIV-1 and HBV coinfection, and we obtained supportive in vitro evidence that entecavir is a potent partial inhibitor of HIV-1 replication. Detailed analysis showed that in one of these patients, entecavir monotherapy led to an accumulation of HIV-1 variants with the lamivudine-resistant mutation, M184V. In vitro experiments showed that M184V confers resistance to entecavir. Until more is known about HIV-1-resistance patterns and their selection by entecavir, caution is needed with the use of entecavir in persons with HIV-1 and HBV coinfection who are not receiving fully suppressive antiretroviral regimens. PMID: 1758207122 A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med 2006; 354(10):1001-10
Chang TT, Gish RG, de Man R, Gadano A, Sollano J, Chao YC, Lok AS, Han KH, Goodman Z, Zhu J, Cross A, DeHertogh D, Wilber R, Colonno R, Apelian D
Entecavir is a potent and selective guanosine analogue with significant activity against hepatitis B virus (HBV). PMID: 1652513723 Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. The Multivirc Group. Hepatology 1999; 30(4):1054-8
Benhamou Y, Bochet M, Di Martino V, Charlotte F, Azria F, Coutellier A, Vidaud M, Bricaire F, Opolon P, Katlama C, Poynard T
The natural history of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patients has never been studied according to the concept of liver fibrosis progression. The aim of this work was to assess the fibrosis progression rate in HIV-HCV coinfected patients and in patients infected by HCV only. A cohort of 122 HIV-HCV coinfected patients was compared with a control group of 122 HIV-negative HCV-infected patients. Groups were matched according to age, sex, daily alcohol consumption, age at HCV infection, and duration and route of HCV infection. The fibrosis progression rate was defined as the ratio between fibrosis stage (METAVIR scoring system) and the HCV duration. The prevalence of extensive liver fibrosis (METAVIR fibrosis scores 2, 3, and 4) and moderate or severe activity were higher in HIV-infected patients (60% and 54%, respectively) than in control patients (47% and 30%, respectively; P <.05 and P <.001, respectively). The median fibrosis progression rate in coinfected patients and in control patients was 0.153 (95% confidence interval [CI], 0.117-0.181) and 0.106 (95% CI, 0.084-0.125) fibrosis units per year, respectively (P <.0001). HIV seropositivity (P <.0001), alcohol consumption (>50 g/d, P =.0002), age at HCV infection (<25 years old, P <.0001), and severe immunosuppression (CD4 count =200 cells/microL, P <.0001) were associated with an increase in the fibrosis progression rate. In coinfected patients, alcohol consumption (>50 g/d), CD4 count (=200 cells/microL), and age at HCV infection (<25 years old) (P <. 0001, respectively) were associated with a higher fibrosis progression rate. HIV seropositivity accelerates HCV-related liver fibrosis progression. In coinfected patients, a low CD4 count, alcohol consumption rate, and age at HCV infection are associated with a higher liver fibrosis progression rate. PMID: 1049865924 Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet 1997; 349(9055):825-32
Poynard T, Bedossa P, Opolon P
Our aim was to assess the natural history of liver fibrosis progression in hepatitis C and the factors associated with this progression. PMID: 912125725 Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients. Gastroenterology 1997; 112(2):463-72
Fattovich G, Giustina G, Degos F, Tremolada F, Diodati G, Almasio P, Nevens F, Solinas A, Mura D, Brouwer JT, Thomas H, Njapoum C, Casarin C, Bonetti P, Fuschi P, Basho J, Tocco A, Bhalla A, Galassini R, Noventa F, Schalm SW, Realdi G
Few data are available concerning the long-term prognosis of chronic liver disease associated with hepatitis C virus infection. This study examined the morbidity and survival of patients with compensated cirrhosis type C. PMID: 902430026 Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis. N Engl J Med 1989; 321(22):1494-500
Alter HJ, Purcell RH, Shih JW, Melpolder JC, Houghton M, Choo QL, Kuo G
We measured antibody (anti-HCV) to hepatitis C virus, which causes non-A, non-B hepatitis, by radioimmunoassay in prospectively followed transfusion recipients and their donors. Of 15 patients with chronic non-A, non-B hepatitis documented by liver biopsy, all seroconverted for the antibody; of 5 with acute resolving non-A, non-B hepatitis, 3 (60 percent) seroconverted. The development of anti-HCV was delayed (mean delay, 21.9 weeks after transfusion, or 15 weeks after the onset of clinical hepatitis) and took approximately one year in one patient. Antibody has persisted in 14 of the 15 patients with chronic disease (mean follow-up, greater than or equal to 6.9 years; maximum, greater than or equal to 12), but has disappeared in the 3 with acute resolving disease after a mean of 4.1 years. Anti-HCV was detected in samples of donor serum given to 14 (88 percent) of the 16 anti-HCV-positive patients for whom all donor samples were available. Only 33 percent of the anti-HCV-positive donors tested had an elevated serum concentration of alanine aminotransferase; 54 percent were positive for antibody to the hepatitis B core antigen (anti-HBc). We conclude that hepatitis C virus is the predominant agent of transfusion-associated non-A, non-B hepatitis and that screening of donors for anti-HCV could prevent the majority of cases of the disease. "Surrogate" assays for anti-HBc and alanine aminotransferase would have detected approximately half the anti-HCV-positive donors involved in the transmission of hepatitis that we identified. PMID: 2509915 |
Dansk Selskab for Tropemedicin og International Sundhed (DSTMIS) generalforsamling 2023
København
Onsdag d. 31. maj
Ph.d. forsvar ved Michaela Tinggaard
Mærsk Tårnet, Panum Instituttet, København
Torsdag d. 1. juni
Ph.d. forsvar ved Carlota Fernández Antúnez
Auditorium 3 og 4, Hvidovre Hospital
Fredag d. 2. juni
European Meeting on HIV & Hepatitis 2023
Rom, Italien
Onsdag d. 7. juni
Houston, Texas, USA
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Tuberkulose - diagnostik og behandling (2023)
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Tuberkuloseinfektion hos immunsupprimerede (2023)
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PLoS One Infectious Diseases
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International Journal of Infectious Diseases
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Mycobacterial Genetic Technologies for Probing the Host-Pathogen Microenvironment
Infection and Immunity
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Virulence
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Journal of Medical Virology
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New Approaches to Chronic Hepatitis B.
Udvalgt og kommenteret af Professor Nina Weis
Tilføjet 19. januar 2023
Udvalgt og kommenteret af Professor Troels Lillebæk
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Bedaquiline-Pretomanid-Linezolid Regimens for Drug-Resistant Tuberculosis.
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Tilføjet 14. januar 2023
Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19.
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Tilføjet 14. december 2022
The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic.
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COVID-19 retningslinje (2022v24)
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Akut bakteriel meningitis (2018)
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Borrelia klaringsrapport (2014)
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Guidelines for diagnostik og behandling af spondylodiskitis (2018)
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