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Adeel A. Butt, Peng Yan, Samia Aslam, Kenneth E. Sherman, Dawd Siraj, Nasia Safdar, Bilal Hameed
Mojca Maticic, Andrea Lombardi, Mario U. Mondelli, Massimo Colombo, ESCMID Study Group for Viral Hepatitis (ESGVH)
Chronic hepatitis C virus (HCV) infection affects 71 million people worldwide. The availability of highly efficient direct acting antivirals has revolutionized the treatment landscape with over 95% cure rates. World Health Organization (WHO) has launched a global program to achieve rather ambitious HCV elimination targets for 2030.
Dezanet L, Maylin S, Gabassi A, et al.
AbstractBackgroundTo describe the kinetics of hepatitis B core-related antigen (qHBcrAg) and anti-hepatitis B core antibody (qAnti-HBc) during tenofovir (TDF)-treatment and assess their ability to predict HBeAg-seroclearance in patients co-infected with HIV and hepatitis B virus (HBV).MethodsSerum qHBcrAg, qAnti-HBc and HBV-DNA were obtained at TDF-initiation and every 6-12 months. On-treatment kinetics of qHBcrAg (ΔqHBcrAg) and qAnti-HBc (ΔqAnti-HBc) were estimated using mixed-effect linear regression. Hazard ratios (HR) assessing the association between markers and HBeAg-seroclearance were calculated using proportional hazards regression and sensitivity (Se) and specificity (Sp) of marker levels in predicting HBeAg-seroclearance were assessed using time-dependent ROC curves.ResultsDuring a median 4.6 years, cumulative incidence of HBsAg-seroclearance and HBeAg-seroclearance were 3.2% (n=5/158) and 27.4% (n=26/95), respectively. ΔqHBcrAg was biphasic in HBeAg-positive (-0.051 and -0.011 log10U/mL/month during 18 months, respectively) and monophasic in HBeAg-negative patients. ΔqAnti-HBc was monophasic regardless of HBeAg-status. In HBeAg-positive patients, baseline qHBcrAg and qAnti-HBc levels were associated with HBeAg-seroclearance (adjusted-HR=0.48/log10U/mL; 95%CI=0.33-0.70 and unadjusted-HR=1.49/log10PEIU/mL; 95%CI=1.08-2.07, respectively). Cutoffs with the highest accuracy in predicting HBeAg-seroclearance at 36 months were qHBcrAg4.1 log10PEIU/mL (Se=0.42/Sp=0.81).ConclusionsIn co-infected patients undergoing TDF, qHBcrAg/qAnti-HBc could be of use in monitoring HBeAg-seroclearance.
Hepatitis B is a major concern in Africa, especially in HIV-infected patients. Unfortunately, access to hepatitis B virus (HBV) testing and adequate treatment remains a challenge in the continent. We investigated HBV testing, treatment, and virologic suppression in HIV-infected patients followed up as part of Cameroon’s national antiretroviral programme.
A cross-sectional survey was performed in adult patients receiving antiretroviral therapy (ART) in 19 hospitals in the Centre and Littoral regions in Cameroon. The proportions of patients tested for hepatitis B surface antigen (HBsAg) prior to the study were compared among all study hospitals using the Chi-square test. The association of individual and hospital-related characteristics with HBV testing and virologic suppression was assessed using multilevel logistic regression models.
Of 1706 patients (women 74%, median age 42 years, median time on ART 3.9 years), 302 (17.7%) had been tested for HBsAg prior to the study. The proportion of HBV-tested patients ranged from 0.8 to 72.5% according to the individual hospital (p
This study sought to provide up-to-date hepatitis B (HBV) and C (HCV) seroprevalence in rural Burkina Faso decade after hepatitis B vaccine was introduced in the national immunization scheduled for children.
In 2018, a community-based, random sampling strategy with probability proportional to population size was conducted in Nanoro to investigate the prevalence of viral hepatitis in children and their mothers. Sociodemographic, vaccination history and risk factors were assessed by interview and health books. HBsAg rapid tests were done by finger prick and Dried Blood Spots (DBS) were collected for hepatitis seromarkers by chemiluminescence enzyme immunoassay. Positive samples underwent confirmatory PCR and phylogenetic analysis.
Data were presented on 240 mother-child pairs. HBsAg Prevalence was 0.8% in children and 6.3% in mothers. Hepatitis B core antibody positivity was 89.2% in mothers, 59.2% in children and was associated with age, sex and scarification. Hepatitis B surface antibodies prevalence was 37.5% in children and 5.8% in mothers. Good vaccination coverage was limited by home delivery. Phylogenetic analysis of HBV strains based on full genome sequences (n = 7) and s-fragment sequences (n = 6) revealed genotype A, E, and recombinant A3/E. Viral genome homology was reported in one mother-child pair. Anti-HCV prevalence was 5.4% in mothers, 2.1% in children and strains belonged to genotype 2.
In Nanoro, HBsAg prevalence was low in children, intermediate in mothers and mother-to-child transmission persists. Home delivery was a limiting factor of Hepatitis B vaccination coverage. HBV genotype E was predominant and genotype A3/E is reported for the first time in Burkina Faso.
Clipman S, Duggal P, Srikrishnan A, et al.
AbstractBackgroundData from high-income countries suggest increasing hepatitis C virus (HCV) prevalence/incidence among HIV-infected men who have sex with men (MSM), but limited data derive from low-and-middle-income countries (LMICs).MethodsWe recruited 4,994 MSM from 5 states across India using respondent-driven sampling (RDS). Logistic regression incorporating RDS weights and machine learning feature selection were used to identify correlates of prevalent HCV, and Bayesian phylogenetic analysis was used to examine genetic clustering.ResultsMedian age was 25, HIV prevalence was 7.2% and 49.3% reported recent unprotected anal intercourse. HCV prevalence was 1.3% (95% CI: 1.0 – 1.6%; site range: 0.2 – 3.4%) and was 3.1% in HIV-positive compared to 1.1% among HIV-negative. HCV infection was significantly associated with injection drug use (OR: 177.1; 95% CI: 72.7 – 431.5) and HIV (OR: 4.34; 95% CI: 1.88 – 10.05). Machine learning did not uncover any additional epidemiologic signal. Phylogenetic analysis revealed three clusters suggestive of linked transmission; each contained at least one individual reporting injection drug use.ConclusionsWe observed a low HCV prevalence in this large sample of MSM despite high prevalence of known risk factors, reflecting either the need for a threshold of HCV for sexual transmission and/or variability in sexual practices across settings.
Greenberg, Lauren; Ryom, Lene; Wandeler, Gilles; Grabmeier-Pfistershammer, Katharina; Öllinger, Angela; Neesgaard, Bastian; Stephan, Christoph; Calmy, Alexandra; Rauch, Andri; Castagna, Antonella; Spagnuolo, Vincenzo; Johnson, Margaret; Stingone, Christof; Mussini, Cristina; De Wit, Stéphane; Necsoi, Coca; Campins, Antoni A.; Pradier, Christian; Stecher, Melanie; Wasmuth, Jan-Christian; Monforte, Antonella d’Arminio; Law, Matthew; Puhr, Rainer; Chkhartishvilli, Nikoloz; Tsertsvadze, Tengiz; Garges, Harmony;
Despite increased INSTI use, limited large-scale, real-life data exists on INSTI uptake and discontinuation.
International multicohort collaboration.
RESPOND participants starting dolutegravir (DTG), elvitegravir (EVG) or raltegravir (RAL) after 1/1/2012 were included. Predictors of INSTI used were assessed using multinomial logistic regression. Kaplan Meier and Cox proportional hazards models describe time to and factors associated with discontinuation.
Overall, 9702 persons were included; 5051 (52.1%) starting DTG, 1933 (19.9%) EVG, 2718 (28.0%) RAL. The likelihood of starting RAL or EVG versus DTG decreased over time and was higher in Eastern and Southern Europe compared to Western Europe.
At 6 months after initiation, 8.9% (95% CI 8.3%-9.5%) had discontinued the INSTI (6.4% DTG, 7.4% EVG, 14.0% RAL). The main reason for discontinuation was toxicity (44.2% DTG, 42.5% EVG, 17.3% RAL). Nervous system toxicity accounted for a higher proportion of toxicity discontinuations on DTG (31.8% DTG, 23.4% EVG, 6.6% RAL). Overall, treatment simplification was highest on RAL (2.7% DTG, 1.6% EVG, 19.8% RAL).
Factors associated with a higher discontinuation risk included increasing year of INSTI initiation, female gender, hepatitis C coinfection, and prior non-AIDS defining malignancies. Individuals in Southern and Eastern Europe were less likely to discontinue. Similar results were seen for discontinuations after 6 months.
Uptake of DTG versus EVG or RAL increased over time. Discontinuation within 6 months was mainly due to toxicity; nervous system toxicity was highest on DTG. Discontinuation was highest on RAL, mainly due to treatment simplification.
Address for Correspondence: Lauren Greenberg Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME) Institute for Global Health, UCL Rowland Hill St, London, NW3 2PF Telephone: 442080168051 Email: firstname.lastname@example.org
Conflicts of Interest and Source of Funding: The International Cohort Consortium of Infectious Disease (RESPOND) has received funding from ViiV Healthcare LLC and Gilead Sciences. Additional support has been provided by participating cohorts contributing data in-kind and/or statistical support: Austrian HIV Cohort Study (AHIVCOS), The Australian HIV Observational Database (AHOD), CHU Saint-Pierre, University Hospital Cologne, The EuroSIDA cohort, Frankfurt HIV Cohort Study, Georgian National AIDS Health Information System (AIDS HIS), Modena HIV Cohort, San Raffaele Scientific Institute, Swiss HIV Cohort Study (SHCS), Royal Free HIV Cohort Study. The authors declare no conflicts of interest.
* The writing committee and RESPOND study group are listed in the Acknowledgments section.
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
Georgia has one of the highest HCV prevalence in the world and launched the world’s first national HCV elimination programs in 2015. Georgia set the ambitious target of diagnosing 90% of people living with HCV, treating 95% of those diagnosed and curing 95% of treated patients by 2020. We report outcomes of Sofosbuvir (SOF) based treatment regimens in patients with chronic HCV infection in Georgia.
Patients with cirrhosis, advanced liver fibrosis and severe extrahepatic manifestations were enrolled in the treatment program. Initial treatment consisted of SOF plus ribavirin (RBV) with or without pegylated interferon (INF). Sustained virologic response (SVR) was defined as undetectable HCV RNA at least 12 weeks after the end of treatment. SVR were calculated using both per-protocol and modified intent-to-treat (mITT) analysis. Results for patients who completed treatment through 31 October 2018 were analyzed.
Of the 7342 patients who initiated treatment with SOF-based regimens, 5079 patients were tested for SVR. Total SVR rate was 82.1% in per-protocol analysis and 74.5% in mITT analysis. The lowest response rate was observed among genotype 1 patients (69.5%), intermediate response rate was achieved in genotype 2 patients (81.4%), while the highest response rate was among genotype 3 patients (91.8%). Overall, SOF/RBV regimens achieved lower response rates than IFN/SOF/RBV regimen (72.1% vs 91.3%, P
Carrero, Ana; Berenguer, Juan; Hontañón, Víctor; Navarro, Jordi; Hernández-Quero, José; Galindo, María J; Quereda, Carmen; Santos, Ignacio; Téllez, María J; Ortega, Enrique; Sanz, José; Medrano, Luz M; Pérez-Latorre, Leire; Bellón, José M; Resino, Salvador; Bermejo, Javier; González-García, Juan; GeSIDA 3603b Study Group
To assess the effects of eradication of HCV on cardiovascular risk and preclinical atherosclerosis in HIV/HCV-coinfected patients.
Prospective cohort study
We assessed serum lipids, 10-year Framingham cardiovascular risk (CVR) scores, pulse wave velocity (PWV), carotid intima-media thickness (cIMT), and biomarkers of inflammation and endothelial dysfunction (BMKs) at baseline and 96 weeks (wk) after initiation of anti-HCV therapy (Rx) in HIV/HCV-coinfected patients.
A total of 237 patients were included. Anti-HCV therapy comprised pegylated interferon and ribavirin (PR) plus 1 direct-acting antiviral (DAA) in 55.2%, PR in 33.8%, and all-oral DAA in 11.0%. A total of 147 (62.0%) patients achieved sustained viral response (SVR). Median increases in low-density lipoprotein cholesterol (LDL-C) in patients with and without SVR were 14 mg/dl and 0 mg/dl (P=.024), respectively. Increases in CVR categories were found in 26.9% of patients with SVR (P=.005 vs. baseline) and 8.1% of patients without SVR (P=.433). This resulted in a significant interaction between SVR and CVR over time (p
H. Sooryanarain et al.
K. E. Coller et al.
Farag M, van Campenhout M, Pfefferkorn M, et al.
AbstractBackgroundHepatitis B virus RNA (HBV-RNA) is a novel serum biomarker that correlates with transcription of intrahepatic covalently closed circular (cccDNA) which is an important target for pegylated interferon (PEG-IFN) and novel therapies for functional cure. We studied HBV-RNA kinetics following PEG-IFN treatment and its potential role as a predictor to response in HBeAg-negative chronic hepatitis B (CHB) patients.MethodsHBV-RNA levels were measured in 133 HBeAg-negative CHB patients treated in an international randomized controlled trial (PARC study). Patients received PEG-IFN α-2a for 48 weeks. HBV-RNA was measured from baseline through week 144. Response was defined as HBV-DNA below 2,000 IU/ml and ALT normalization at week 72. Kinetics of HBV-RNA were compared with HBV-DNA, HBsAg, and HBcrAg.ResultsMean HBV-RNA at baseline was 4.4 (SD 1.2) log10 c/mL. At week 12, HBV-RNA declined by -1.6 (1.1) log10 c/mL. HBV-RNA showed a greater decline in responders compared to non-responders early at week 12 (-2.0 [1.2] vs -1.5 [1.1] log10 c/mL, P=0.04). HBV-RNA level above 1700 c/mL (3.2 log10 c/mL) had a negative predictive value of 91% at week 12 and 93% at week 24 (P=0.01) for response. Overall, HBV-RNA showed a stronger correlation with HBV-DNA and HBcrAg (0.82 and 0.80, P
Nucleic acid hybridization (NAH) of hepatitis C virus (HCV) is a practical and reliable tool for virus genotyping. Genotype assignment is an important factor in the prediction of treatment success in chronic hepatitis C patients. The aim of this study was to determine the genotype distribution among HCV clinical isolates in Jordan between 2007 and 2018.
Electronic and paper-based clinical data registry records from 2007 to 2018 at the Jordan University Hospital (JUH) were retrospectively examined for individuals with HCV genotype, HCV viral load, and alanine aminotransferase (ALT) testing results. Genotype determination was based on NAH technique using the HCV 5′ untranslated region (5′ UTR) with 386 requests available from 342 unique individuals.
A total of 263 out of 342 unique individuals (76.9%) had genotyping results available for final analysis with 259 individuals each having a single genotyping result. The most common HCV genotypes in the study were: genotype 4 (n = 142, 54.0%), genotype 1 (n = 87, 33.1%), genotype 3 (n = 16, 6.1%), genotype 2 (n = 9, 3.4%), other undetermined genotypes (n = 5, 1.9%) and mixed infections (n = 4, 1.5%). Sub-genotyping results were available for 46 individuals as follows: sub-genotype 4c/d (n = 13, 28.3%), sub-genotype 1a (n = 11, 23.9%), sub-genotype 1b (n = 10, 21.7%), sub-genotype 4a (n = 8, 17.4%), sub-genotype 3a (n = 2, 4.3%), sub-genotypes 2a/c and 4 h (n = 1, 2.2% for both). Individuals infected with genotype 1 showed higher viral load when compared to those infected with genotype 4 (p = 0.048, t-test). Younger HCV-infected individuals (
Loffredo-Verde E, Bhattacharjee S, Malo A, et al.
AbstractBackgroundChronic hepatitis B develops more frequently in countries with high prevalence of helminth infections. The crosstalk between these 2 major liver-residing pathogens, Schistosoma mansoni and hepatitis B virus (HBV), is barely understood.MethodsWe used state-of-the-art models for both acute and chronic HBV infection to study the pathogen-crosstalk during the different immune phases of schistosome infection. ResultsAlthough liver pathology caused by schistosome infection was not affected by either acute or chronic HBV infection, S mansoni infection influenced HBV infection outcomes in a phase-dependent manner. Interferon (IFN)-γ secreting, HBV- and schistosome-specific CD8 T cells acted in synergy to reduce HBV-induced pathology during the TH1 phase and chronic phase of schistosomiasis. Consequently, HBV was completely rescued in IFN-γ-deficient or in TH2 phase coinfected mice demonstrating the key role of this cytokine. It is interesting to note that secondary helminth infection on the basis of persistent (chronic) HBV infection increased HBV-specific T-cell frequency and resulted in suppression of virus replication but failed to fully restore T-cell function and eliminate HBV.ConclusionsThus, schistosome-induced IFN-γ had a prominent antiviral effect that outcompeted immunosuppressive effects of TH2 cytokines, whereas HBV coinfection did not alter schistosome pathogenicity.
Lachmann, Gunnar; Knaak, Cornelia; Vorderwülbecke, Gerald; La Rosée, Paul; Balzer, Felix; Schenk, Thomas; Schuster, Friederike S.; Nyvlt, Peter; Janka, Gritta; Brunkhorst, Frank M.; Keh, Didier; Spies, Claudia
Hyperferritinemia is frequently seen in critically ill patients. A rather rare though life-threatening condition related to severely elevated ferritin is hemophagocytic lymphohistiocytosis. We analyze ferritin levels to differentiate hemophagocytic lymphohistiocytosis from other causes of hyperferritinemia in a mixed cohort of critically ill patients.
Retrospective observational study.
Adult surgical, anesthesiologic, and medical ICUs of a university hospital.
Critical care patients (≥ 18 yr old) admitted to any of the adult ICUs at Charité – Universitätsmedizin Berlin between January 2006 and August 2018 with at least one ferritin value and hyperferritinemia (≥ 500 µg/L).
Measurements and Main Results:
Patients were categorized into hemophagocytic lymphohistiocytosis, sepsis, septic shock, and other diagnoses. These were further categorized into 17 subgroups. Hemophagocytic lymphohistiocytosis diagnosis was based on Hemophagocytic Lymphohistiocytosis-2004 criteria and the HScore. Of 2,623 patients with hyperferritinemia, 40 were considered to have hemophagocytic lymphohistiocytosis (1.52%). Maximum ferritin levels were highest in hemophagocytic lymphohistiocytosis patients compared with all other disease groups (each p < 0.001). Sepsis and septic shock patients had higher maximum ferritin levels than patients with other diagnoses (each p < 0.001). A maximum ferritin value of 9,083 µg/L was at 92.5% sensitivity and 91.9% specificity for hemophagocytic lymphohistiocytosis (area under the curve, 0.963; 95% CI, 0.949–0.978). Of all subgroups with other diagnoses, maximum ferritin levels were highest in patients with varicella-zoster virus, hepatitis, or malaria (median, 1,935, 1,928, and 1,587 µg/L, respectively). Maximum ferritin levels were associated with increased in-hospital mortality (odds ratio, 1.518 per log µg/L [95% CI, 1.384–1.665 per log µg/L]; p < 0.001).
This is the largest study of patients with ferritin available in a mixed ICU cohort. Ferritin levels in patients with hemophagocytic lymphohistiocytosis, sepsis, septic shock, and other conditions were distinctly different, with the highest ferritin levels observed in hemophagocytic lymphohistiocytosis patients. Maximum ferritin of 9,083 µg/L showed high sensitivity and specificity and, therefore, may contribute to improved diagnosis of hemophagocytic lymphohistiocytosis in ICU. The inclusion of ferritin into the sepsis laboratory panel is warranted.
Drs. Lachmann and Knaak contributed equally to this work.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).
Dr. Lachmann is a participant of the Berlin Institute of Health (BIH) Charité Clinician Scientist Program funded by the Charité – Universitätsmedizin Berlin and the BIH. Prof. Balzer’s institution received funding from Einstein Foundation and Clearflow, and he received funding from Medtronic. Prof. Spies’ institution received funding from BIH (Clinician Scientist Program). The remaining authors have disclosed that they do not have any potential conflicts of interest.
For information regarding this article, E-mail: email@example.com
Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Jiawen Wang, Panli Zhang, Jinfeng Zeng, Peng Du, Xin Zheng, Xianlin Ye, Weigang Zhu, Yongshui Fu, Daniel Candotti, Jean-Pierre Allain, Chengyao Li, Tingting Li
The story of hepatitis B is as fascinating as it is devastating. Chronic hepatitis B and acute liver failure deaths claim 900 000 people globally each year, and another 237 million people live with chronic hepatitis B virus (HBV) infection, including 2·2 million in the USA. HBV replication in hepatocytes can cause cirrhosis and hepatocellular carcinoma in nearly a third of chronically infected adults. More than 80% of infants who are vertically infected through maternal blood develop chronic hepatitis B and might require life-long treatment.
Fatma Amer, Monkez M. Yousif, Heba Mohtady, Rania A. Khattab, Ergenekon Garagoz, Khan F.M. Ayaz, Noha M. Hammad
Butt A, Yan P, Aslam S, et al.
AbstractFor persons with baseline Fibrosis-4 1.46–3.25, cirrhosis incidence/1000 patient-years was 49.3 among hepatitis B virus (HBV)/hepatitis C virus (HCV) coinfected and 18.2 among HCV monoinfected (P = .03). Cirrhosis risk was numerically higher but statistically nonsignificant among HBV/HCV coinfected (hazards ratio [HR] 1.51; 95% confidence intervals [CI], .37–6.05) but lower among those who attained sustained virologic response (HR, .52; 95% CI, .42–.63).
Mohammed Eslam, Rino Alvani, Gamal Shiha
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease, affecting about a quarter of the global population.c Non-alcoholic steatohepatitis (NASH), the progressive form of NAFLD, is characterised by hepatic inflammation with balloon degeneration, and portends progression to fibrosis and cirrhosis. Some people with NASH can develop hepatocellular carcinoma, even those who do not have cirrhosis. NASH is a multisystem disease; although it is on course to become the main indication for liver transplantation,2 it also increases the risk of type 2 diabetes and cardiovascular disease.
Zobair M Younossi, Vlad Ratziu, Rohit Loomba, Mary Rinella, Quentin M Anstee, Zachary Goodman, Pierre Bedossa, Andreas Geier, Susanne Beckebaum, Philip N Newsome, David Sheridan, Muhammad Y Sheikh, James Trotter, Whitfield Knapple, Eric Lawitz, Manal F Abdelmalek, Kris V Kowdley, Aldo J Montano-Loza, Jerome Boursier, Philippe Mathurin, Elisabetta Bugianesi, Giuseppe Mazzella, Antonio Olveira, Helena Cortez-Pinto, Isabel Graupera, David Orr, Lise Lotte Gluud, Jean-Francois Dufour, David Shapiro, Jason Campag
Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes.
Epstein RL, Wang J, Hagan L, et al.
This study characterizes hepatitis C virus (HCV) testing and the HCV care cascade among 13- to 21-year-olds accessing US federally qualified health centers.
M. Kaddoura et al.
Besson, Caroline; Noel, Nicolas; Lancar, Remi; Prevot, Sophie; Algarte-Genin, Michele; Rosenthal, Eric; Bonnet, Fabrice; Meyohas, Marie-Caroline; Partisani, Marialuisa; Oberic, Lucie; Gabarre, Jean; Goujard, Cécile; Cheret, Antoine; Arvieux, Cedric; Katlama, Christine; Salmon, Dominique; Boué, François; Costello, Regis; Hendel-Chavez, Houria; Taoufik, Yassine; Fontaine, Hélène; Coppo, Paul; Mounier, Nicolas; Delobel, Pierre; Costagliola, Dominique; on behalf of the Lymphovir and FHDH study groups
Chronic hepatitis C virus (HCV) and hepatitis virus (HBV) infections are associated with increased risks of lymphomas in the non-HIV setting. Their impacts on HIV-associated lymphomas deserved further studies in the modern combined antiretroviral therapy (cART) era.
We evaluated the associations between HCV, HBV and HIV-related lymphomas in the Lymphovir-ANRS-CO16 cohort.
Prevalence of HCV-seropositivity and chronic HBV infections were compared to those observed in the French Hospital Database on HIV (FHDH-ANRS-CO4).
Between 2008 and 2015, 179 patients with HIV-related lymphomas from 32 French hospitals were enrolled, 69 had Hodgkin's lymphoma (HL) (39%), and 110 non-Hodgkin's lymphoma (NHL) (61%). The prevalence of HCV infection was higher in patients with NHL than in the FHDH-ANRS-CO4 (26% versus 14%, Odd-Ratio (OR): 2.15; 95% confidence interval [1.35–3.32]) while there was no association between HL and chronic HCV infection. Chronic HBV infection was not associated with NHL in our cohort with a prevalence of 5% versus 7% in FHDH-ANRS-CO4 but tended to be associated with HL (prevalence of 14%, OR: 2.16 [0.98–4.27]). Chronic HCV infection tended to pejoratively impact 2-year overall survival in patients with NHL: 72% [57%, 91%] versus 82% [74%, 91%], Hazard-ratio: 2.14 [0.95–4.84]. In contrast, chronic HBV infection did not correlate with outcome.
In the modern cART era, chronic HCV infection is associated with an increased risk of NHL in PLWHIV and tends to pejoratively impact overall survival. HBV infection is not associated with the risk of NHL but with a borderline increase of HL risk.
Correspondence to Caroline Besson, MD, PhD, Hematology-Oncology Unit, Centre Hospitalier de Versailles, 177 rue de Versailles, 78150 Le Chesnay, France. Tel: +33 139 638 511; fax: +33 139 639 408; e-mail: firstname.lastname@example.org.Alternatecorrespondingauthor:DominiqueCostagliola,UMRS1136,INSERM,56BdVAuriol,CS81393,75646ParisCedex13,France,Tel.:+33142164282;fax:+33142164261;e-mail:email@example.com
Received 26 July, 2019
Revised 5 November, 2019
Accepted 11 November, 2019
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com).
Copyright © 2019 Wolters Kluwer Health, Inc.
Young Kyung Lee,
Dong Jun Oh,
Hyo Geun Choi
Journal of Medical Virology, Volume 0, Issue ja, -Not available-.
Ramirez, S., Fernandez-Antunez, C., Mikkelsen, L. S., Pedersen, J., Li, Y.-P., Bukh, J.
Introduction of highly efficient therapies with direct-acting antivirals (DAA) for patients with chronic hepatitis C virus (HCV) infection offers exceptional opportunities to globally control this deadly disease. For achieving this ambitious goal, it is essential to prevent antiviral resistance against the most optimal first-line and retreatment DAA choices. We performed independent comparisons of the efficacy and barrier to resistance of pangenotypic DAA regimens for HCV genotype 2 infections, using previously, and newly developed efficient cell culture adapted strains of subtypes 2a, 2b and 2c. With applied experimental cell culture conditions, combination treatment with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir DAA-regimens was efficient in eradicating HCV infections, in contrast to single drug treatments frequently leading to viral escape. Sequence analysis of drug targets from recovered viruses revealed known resistance associated substitutions (RAS) emerging in the NS3 protease or NS5A after treatment failure, which were genetically stable after viral passage and exhibited significant phenotypic resistance. After sofosbuvir treatment failure, only a genotype 2a virus harbored NS5B-RAS S282T and thus had decreased susceptibility to nucleotide analogs (nucs). However, in most cases viral escape from sofosbuvir led to other NS5B substitutions with maintained drug susceptibility, and in one case no changes in NS5B were detected. For a genotype 2b virus, after treatment failure with sofosbuvir/velpatasvir, retreatment with glecaprevir/pibrentasvir maintained efficacy due to the high barrier to resistance and low cross-resistance of pibrentasvir. Our findings suggest slight superiority of glecaprevir/pibrentasvir for genotype 2b in culture, which could have potential therapeutic interest meriting more definitive investigations in the clinic.
Singh K, Lewin S.
Leumi S, Bigna J, Amougou M, et al.
AbstractBackgroundThis systematic review and meta-analysis was conducted to estimate the prevalence and burden of HBV infection in PLWH at global, regional, and national levels.MethodsWe searched of PubMed, Excerpta Medica Database, Web of Science, and Global Index Medicus to identify studies published between January 01, 1990 and December 31st, 2017. HBV infection (HBs antigen) had to be diagnosed with serological assays. Random-effect models meta-analysis served to pool data.ResultsWe included 358 studies (834,544 PLWH from 87 countries). The pooled prevalence of HBV infection was 8.4% (95% confidence interval: 7.9-8.8); among which 26.8% (22.0-31.9) were positive to HBe antigen. The HBV prevalence was different according to UNAIDS regions: West & Central Africa: 12.4% (11.0-13.8), Middle East & North Africa: 9.9% (6.0-14.6), Asia & the Pacific: 9.8% (8.7-11.0), Eastern & Southern Africa: 7.4% (6.4-8.4), Western and Central Europe & North America: 6.0% (5.5-6.7), and Latin America & the Caribbean: 5.1% (4.2-6.2); p < 0.0001. The prevalence decreased from 10.4% in low to 6.6% in very high developed countries; p < 0.0001 and increased from 7.3% in countries with HIV prevalence ≤ 1% to 9.7% in countries with HIV prevalence > 1%; p < 0.0001. Globally, we estimated that there were roughly 3,136,500 (95%CI: 2,95,2000-3,284,100) cases of HBV in PLWH; with 73.8% of estimated regional cases from sub-Saharan Africa and 17.1% from Asia & the Pacific.ConclusionsThis study suggests a high burden of HBV infection in PLWH, with disparities according to regions, level of development, and country HIV prevalence.
Journal of Medical Virology, EarlyView.
Grace L.‐H. Wong,
Margo J. H. Campenhout,
Vincent W.‐S. Wong,
Terry C.‐F. Yip,
Henry L.‐Y. Chan
Journal of Medical Virology, Volume 92, Issue 1, Page 62-70, January 2020.
Journal of Medical Virology, Volume 92, Issue 1, Page 124-127, January 2020.
Kamar N, Abravanel F, Behrendt P, et al.
AbstractBackgroundRibavirin is currently recommended for treating chronic hepatitis E virus (HEV) infection. This retrospective European multicenter study aimed to assess the sustained virological response (SVR) in a large cohort of solid organ transplant (SOT) recipients with chronic HEV infection treated with ribavirin monotherapy (N = 255), to identify the predictive factors for SVR, and to evaluate the impact of HEV RNA mutations on virological response.MethodsData from 255 SOT recipients with chronic HEV infection from 30 European centers were analyzed. Ribavirin was given at the median dose of 600 (range, 29–1200) mg/day (mean, 8.6 ± 3.6 mg/kg/day) for a median duration of 3 (range, 0.25–18) months.ResultsAfter a first course of ribavirin, the SVR rate was 81.2%. It increased to 89.8% when some patients were offered a second course of ribavirin. An increased lymphocyte count at the initiation of therapy was a predictive factor for SVR, while poor hematological tolerance of ribavirin requiring its dose reduction (28%) and blood transfusion (15.7%) were associated with more relapse after ribavirin cessation. Pretreatment HEV polymerase mutations and de novo mutations under ribavirin did not have a negative impact on HEV clearance. Anemia was the main adverse event.ConclusionsThis large-scale retrospective study confirms that ribavirin is highly efficient for treating chronic HEV infection in SOT recipients and shows that the predominant HEV RNA polymerase mutations found in this study do not affect the rate of HEV clearance.This large-scale retrospective study that included 255 solid organ transplant recipients confirms that ribavirin is highly efficient for treating chronic hepatitis E virus (HEV) infection and shows that HEV RNA polymerase mutations do not play a role in HEV clearance.
Viral hepatitis is a global public health problem affecting millions of people worldwide, causing thousands of deaths due to acute and persistent infection, cirrhosis, and liver cancer. Providing updated serologic data can improve both surveillance and disease control programs. This study is aimed to determine the seroprevalence of markers for viral hepatitis (A, B, C, D and E) and the epidemiology of such infections in the general population of southern Iran’s Hormozgan province.
Between 2016 and 2017, a total of 562 individuals with ages ranging from 1 to 86 years, who visited governmental public laboratories for routine check-ups, were tested for the presence of serological markers to hepatitis virus types A to E using enzyme-linked immunosorbent assays.
The overall anti-hepatitis A virus (HAV) antibody seroprevalence was 93.2% (524/562). The prevalence of anti-hepatitis E virus (HEV) antibodies was 15.8% (89/562) among which 1.6% (9/562) of the seropositive individuals also had evidence of recent exposure to the virus (IgM positivity). Two and a half percent (14/562) were positive for hepatitis B surface (HBs) antigen, whereas 11.6% (65/562) tested positive for anti-hepatitis B core (HBc) antibodies. Among anti-HBc positive patients, 11% (7/65) had HBs Ag and 5% (3/65) were positive for anti-hepatitis D virus (HDV) antibodies. The prevalence of anti-hepatitis C virus (HCV) antibodies was 0.7% (4/562). The seroprevalence of anti-HAV, HEV IgG, anti-HBc antibodies, and HBs Ag increased with age.
The present study confirms a high seroprevalence of HAV infection among the examined population and reveals high levels of endemicity for HEV in the region. Planned vaccination policies against HAV should be considered in all parts of Iran. In addition, improvements on public sanitation and hygiene management of drinking water sources for the studied area are recommended.
Few countries in sub-Saharan Africa know the magnitude of their HIV epidemic among people who inject drugs (PWID). This was the first study in Mozambique to measure prevalence of HIV, HBV, and HCV, and to assess demographic characteristics and risk behaviors in this key population.
We used respondent-driven sampling (RDS) to conduct a cross-sectional behavioral surveillance survey of PWID in two cities of Mozambique lasting six months. Participants were persons who had ever injected drugs without a prescription. Participants completed a behavioral questionnaire and provided blood specimens for HIV, hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (anti-HCV) testing. We performed RDS-adjusted analysis in R 3.2 using RDSAT 7.1 weights.
We enrolled 353 PWID in Maputo and 139 in Nampula/Nacala; approximately 95% of participants were men. Disease prevalence in Maputo and Nampula/Nacala, respectively, was 50.1 and 19.9% for HIV, 32.1 and 36.4% for HBsAg positivity, and 44.6 and 7.0% for anti-HCV positivity. Additionally, 8% (Maputo) and 28.6% (Nampula/Nacala) of PWID reported having a genital sore or ulcer in the 12 months preceding the survey. Among PWID who injected drugs in the last month, 50.3% (Maputo) and 49.6% (Nampula/Nacala) shared a needle at least once that month. Condomless sex in the last 12 months was reported by 52.4% of PWID in Maputo and 29.1% in Nampula/Nacala. Among PWID, 31.6% (Maputo) and 41.0% (Nampula/Nacala) had never tested for HIV. In multivariable analysis, PWID who used heroin had 4.3 (Maputo; 95% confidence interval [CI]: 1.2, 18.2) and 2.3 (Nampula/Nacala; 95% CI: 1.2, 4.9) greater odds of having HIV.
Unsafe sexual behaviors and injection practices are frequent among PWID in Mozambique, and likely contribute to the disproportionate burden of disease we found. Intensified efforts in prevention, care, and treatment specific for PWID have the potential to limit disease transmission.
Chronic hepatitis C is a major public health burden. With new interferon-free direct-acting agents (showing sustained viral response rates of more than 98%), elimination of HCV seems feasible for the first time. However, as HCV infection often remains undiagnosed, screening is crucial for improving health outcomes of HCV-patients. Our aim was to assess the long-term cost-effectiveness of a nationwide screening strategy in Germany.
We used a Markov cohort model to simulate disease progression and examine long-term population outcomes, HCV associated costs and cost-effectiveness of HCV screening. The model divides the total population into three subpopulations: general population (GEP), people who inject drugs (PWID) and HIV-infected men who have sex with men (MSM), with total infection numbers being highest in GEP, but new infections occurring only in PWIDs and MSM. The model compares four alternative screening strategies (no/basic/advanced/total screening) differing in participation and treatment rates.
Total number of HCV-infected patients declined from 275,000 in 2015 to between 125,000 (no screening) and 14,000 (total screening) in 2040. Similarly, lost quality adjusted life years (QALYs) were 320,000 QALYs lower, while costs were 2.4 billion EUR higher in total screening compared to no screening. While incremental cost-effectiveness ratio (ICER) increased sharply in GEP and MSM with more comprehensive strategies (30,000 EUR per QALY for total vs. advanced screening), ICER decreased in PWIDs (30 EUR per QALY for total vs. advanced screening).
Screening is key to have an efficient decline of the HCV-infected population in Germany. Recommendation for an overall population screening is to screen the total PWID subpopulation, and to apply less comprehensive advanced screening for MSM and GEP.
Stephen A Harrison, Mustafa R Bashir, Cynthia D Guy, Rong Zhou, Cynthia A Moylan, Juan P Frias, Naim Alkhouri, Meena B Bansal, Seth Baum, Brent A Neuschwander-Tetri, Rebecca Taub, Sam E Moussa
Resmetirom treatment resulted in significant reduction in hepatic fat after 12 weeks and 36 weeks of treatment in patients with NASH. Further studies of resmetirom will allow assessment of safety and effectiveness of resmetirom in a larger number of patients with NASH with the possibility of documenting associations between histological effects and changes in non-invasive markers and imaging.
Traditionally, non-alcoholic steatohepatitis (NASH) has been associated with insulin resistance-related clinical conditions, such as overweight and type 2 diabetes. However, a quantitative association between subclinical low thyroid function and hepatic steatosis has been shown in a population-based study1 and in a study of people with type 2 diabetes,2 which is independent of metabolic comorbidities.3 Incident steatosis occurs more often with higher baseline thyrotropin concentrations.4,5 In rodents, mild hypothyroidism increases adipose tissue lipolysis, with subsequent hepatic fat accumulation.
Yurdaydin C, Toy M.
Miao Z, Zhang S, Ou X, et al.
AbstractBackgroundHepatitis delta virus (HDV) co-infects with hepatitis B virus (HBV) causing the most severe form of viral hepatitis. However, its exact global disease burden remains largely obscure. We aim to establish the global epidemiology, infection mode-stratified disease progression and clinical outcome of HDV infection.MethodsWe conducted a meta-analysis with a random-effects model, and performed data synthesis.ResultsThe pooled prevalence of HDV is 0.80% (95% CI 0.63-1.00) among the general population and 13.02% (95% CI 11.96-14.11) among HBV carriers, corresponding to 48-60 million infections globally. Among HBV patients with fulminant hepatitis, cirrhosis or hepatocellular carcinoma, HDV prevalence is 26.75% (95% CI 19.84-34.29), 25.77% (95% CI 20.62-31.27), and 19.80% (95% CI 10.97-30.45), respectively. The odds ratio (OR) of HDV infection among HBV patients with chronic liver disease compared to asymptomatic controls is 4.55 (95% CI 3.65-5.67). HDV co-infected patients are more likely to develop cirrhosis than HBV mono-infected patients with OR of 3.84 (95% CI 1.79-8.24). Overall, HDV infection progresses to cirrhosis within 5 years, and to hepatocellular carcinoma within 10 years in average.ConclusionsFindings suggest that HDV poses a heavy global burden with rapid progression to severe liver diseases, urging effective strategies for screening, prevention and treatment.
Ogawa E, Toyoda H, Iio E, et al.
AbstractBackgroundThe cure rate of hepatitis C virus (HCV) treatment with direct-acting antivirals (DAAs) for patients with active and inactive hepatocellular carcinoma (HCC) may differ, but well-controlled studies are limited. We aimed to evaluate DAA outcomes in a large East Asian HCV/HCC population compared to HCV/non-HCC patients.MethodsUsing data from the REAL-C registry (Hong Kong, Japan, South Korea, and Taiwan), we used propensity score matching (PSM) to match HCC and non-HCC (1:1) groups for age, sex, cirrhosis, prior treatment, HCV genotype, treatment regimen, baseline platelet count, HCV RNA, total bilirubin, alanine aminotransferase, and albumin level to evaluate DAA treatment outcomes in a large population of HCV/HCC compared to HCV/non-HCC patients.ResultsWe included 6,081 patients (HCC, n=465; non-HCC, n=5,616) treated with interferon-free DAAs. PSM of the entire study population yielded 436 matched pairs with similar baseline characteristics. There was no statistically significant difference in the overall SVR rate of the HCC (92.7%) and non-HCC (95.0%) groups. Rates of treatment discontinuation, adverse effects, and death were also similar between the HCC and non-HCC groups. Among patients with HCC, those with active HCC had a lower SVR than inactive HCC cases (85.5% vs. 93.7%, P=0.03). On multivariable analysis, active HCC, but not inactive HCC, was significantly associated with lower SVR (OR 0.28, P=0.01) when compared to non-HCC.ConclusionsActive HCC but not inactive HCC was independently associated with lower SVR compared to non-HCC patients undergoing DAA therapy, though cure rate was still relatively high (85%) in active HCC patients.
Elliott, Tamara; Cooke, Graham S.; Garvey, Lucy
Purpose of review
The WHO has set ambitious targets for hepatitis C virus (HCV) elimination by 2030. In this review, we explore the possibility of HCV micro-elimination in HIV-positive (+) MSM, discussing strategies for reducing acute HCV incidence and the likely interventions required to meet these targets.
With wider availability of directly acting antivirals (DAAs) in recent years, reductions in acute HCV incidence have been reported in some cohorts of HIV+ MSM. Recent evidence demonstrates that treatment in early infection is well tolerated, cost effective and may reduce the risk of onward transmission. Modelling studies suggest that to reduce incidence, a combination approach including behavioural interventions and access to early treatment, targeting both HIV+ and negative high-risk groups, will be required. HCV vaccine trials have not yet demonstrated efficacy in human studies, however phase one and two studies are ongoing.
Some progress towards the WHO HCV elimination targets has been reported. Achieving sustained HCV elimination is likely to require a combination approach including early access to DAAs in acute infection and reinfection, validated and reproducible behavioural interventions and an efficacious HCV vaccine.
Correspondence to Lucy Garvey, Jefferiss Wing, St Mary's Hospital, Imperial College Healthcare NHS Trust, London W2 1NY, UK. E-mail: firstname.lastname@example.org
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Bo Langhoff Hønge,
Jens Steen Olesen,
Mads Mose Jensen,
Zacarias José Silva,
Alex Lund Laursen,
Tropical Medicine &International Health, EarlyView.
The prizes, given annually for achievements in medicine and public health, have gone this year to scientists working on hepatitis C virus and trachoma. Talha Burki reports.
Nativa Helena Alves Del‐Rios,
Lyriane Apolinário Araujo,
Regina Maria Bringel Martins,
Rafael Alves Guimarães,
Márcia Alves Dias Matos,
Karlla Antonieta Amorim Caetano,
Raquel Silva Pinheiro,
Divânia Dias da Silva França,
Leandro Nascimento da Silva,
Sheila Araújo Teles,
Megmar Aparecida dos Santos Carneiro
Specialespecifikt kursus om immundefekt og feber af ukendt årsag
28.01.2020 - 29.01.2020
International Congress on Infectious Diseases (ICID) 2020
Kuala Lumpur, Malaysia
20.02.2020 - 23.02.2020
Dansk Selskab for Intern Medicin (DSIM) årsmøde og overrækkelse af Hagedorn prisen 2020
Novo Nordisk Fonden, Tuborg Havnevej 19, 2900 Hellerup
Conference on Retroviruses and Opportunistic Infections (CROI) 2020
Boston, Massachusetts, USA
8.03.2020 - 11.03.2020
Når CROI går i fisk - med transmissioner fra CROI 2020
10.03.2020 - 11.03.2020
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Sensory nociceptive neurons contribute to host protection during enteric infection with Citrobacter rodentium
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