Objectives Given the complications from cancer treatment affecting children, adolescents and young adults, it is essential to establish individualized and progressive survivorship care plans (SCPs). Implementing current evidence-based guidelines into clinical practice can contribute to a personalised approach. To support this person-centered care, a digital tool was developed through a participatory approach in the GOCE network (Western region Childhood Cancer in France) and distributed to other comprehensive French cancer centers (LOG-after).This INCa-funded THINK-project aimed to compare the SCPs generated by LOG-after with those proposed by oncologists, pediatric oncologists and radiation oncologists. Study design A questionnaire comprising 3 clinical cases (acute lymphoblastic leukemia, Hodgkin's lymphoma, nephroblastoma) was circulated among 3 national networks (SFCE, AYA group, Pediatric radiotherapy). Responses were compared with SCPs generated by LOG-after, and attitudes were discussed in workshops. Results Thirty-six practitioners participated, including 5 radiation oncologists. Thirteen respondents considered themselves experts in survivorship care. SCP varied significantly between practitioners with no complete agreement. However, there was greater alignment between the software and practitioners for high-grade recommendations, particularly among experts (e.g., 100% of experts recommended post-anthracycline cardiac monitoring). Conclusion Given the observed heterogeneity, the LOG-after tool, which integrates the latest recommendations, is expected to improve SCP by enhancing consistency and reducing unnecessary screenings. During the workshops, participants considered the algorithm to be generally aligned with published guidelines, confirming its potential to facilitate their broader dissemination. This digital tool can help standardize evidence-based survivorship care, and potentially increase consistency in monitoring and potentially lead to better long-term health outcomes for cancer survivors

Patients living with HIV infection (PLWH) are at risk of acquiring HBV and HDV. The present study aimed to determine the prevalence and characteristics of HIV-HDV-HBV tri-infection in comparison with HIV-HBV coinfection and to estimate severities and outcomes of associated liver diseases in Mauritanian PLWH. Two-hundred-ninety-two consecutive HBsAg-positive PLWH were included (mean age: 37 years). Clinical data were recorded. Anti-HDV antibodies, HBV and HDV viral loads (VLs) and genotype were determined. APRI, FIB-4 and FibroScan were performed to evaluate the severity of liver disease. The anti-HDV antibodies prevalence was 37% and HDV RNA was positive in 40.7% of patients. Genetic diversities were found with HDV genotype 1 (93%) and HBV genotypes D (42.5%) and E (38%). The HBV VL was detectable in 108 patients at inclusion, and mutations associated with HBV resistance were found in 20. For almost all variables studied, including FIB-4 and APRI scores, no significant differences were found between anti-HDV-Ab positive or negative patients. FibroScan examination, which was performed in 110 patients at end-of-follow-up showed higher, but NS values, in HDV positive patients. After a mean follow-up of 24.55 ± 8.01 months (n = 217 patients), a highly significant worsening of APRI and FIB-4 scores was found. Moreover, patients with HDV showed more severe liver disease progression despite an efficient therapy. In a substantial Mauritanian cohort of relatively young PLWH, we found high HDV prevalence and worsening liver disease. In high-risk countries, screening for HDV and providing appropriate follow-up and treatments are warranted in PLWH.

Background Treatment summaries and a personalized survivorship care plans based on internationally approved, organ-specific follow-up care recommendations are essential in preserving the health and quality of life for cancer survivors. Cohorts made up of survivors of childhood cancer have made significant contributions to the understanding of early mortality, somatic late complications, and psychosocial outcomes among former patients. New treatment protocols are needed to enhance survival and reduce the potential risk and severity of late effects, and working with treatment databases is crucial in doing so. Construction and content In the GOCE (Grand Ouest Cancer de l’Enfant [Western Region Childhood Cancer]) network, in a participative approach, we developed the LOG-after medical tool, on which health data are registered and can be extracted for analysis. Its name emphasizes the tool’s goal, referring to ‘logiciel’ (the French word for software) that focuses on the period “after” the acute phase. This tool is hosted on a certified health data server. Several interfaces have been developed that can be used depending on the user’s profile. Here we present this innovative co-constructed tool that takes national aspects into account, including the results of the feasibility/satisfaction study and its perspective. Utility and discussion The database contains data relating to 2558 patients, with samples from 1702 of these (66.54%) being held in a tumor bank. The average year in which treatment started was 2015 (ranging from December 1967 to November 2022: 118 patients were treated before 2012 and registered retrospectively when seen in long-term follow-up consultations or for another cancer since November 2021). A short questionnaire was distributed to healthcare professionals using the tool (physicians and research associates or technicians, n = 14), of whom 11 answered and were all satisfied. Access to the patient interface is currently open to 124 former patients. This was initially offered to 30 former patients who were over 15 years old, affected by the disease within the last 5 years, and had agreed to test it. Their opinions were collected by their doctor by e-mail, telephone, or during a consultation in an open-ended question and a non-directive interview. All patients were satisfied with the tool, with interest in testing it in the long term. Some former patients found that the tool provided them with some ease of mind; one, for instance, commented: "I feel lighter. I allow myself to forget. I know I will get a notification when the time comes." Conclusions Freely available to all users, LOG-after: (1) provides help with determining personalized survivorship care plans for follow-up; (2) builds links with general practitioners; (3) empowers the patient; and (4) enables health data to be exported for analysis. Database URL for presentation: https://youtu.be/2Ga64iausJE

Abstract Background Treatment summary and a personalized survivorship care plan based on internationally approved, organ-specific follow-up care recommendations are essential to preserve health and quality of life. Cohorts have made significant contributions to the understanding of early mortality, somatic late complications, and psychosocial outcomes among childhood cancer survivors. New treatment protocols have the goal to increase the cure and reduce the potential risk and severity of late effects. Therefore, pursue such databases with modern treatments are necessary. Construction and content In the GOCE network, in a participative approach, we developed the LOG-after medical tool, on which health data are registered and can be extracted for analysis. This tool is hosted on a web server, which is health data host certified and several interfaces have been developed depending on the user’s profile. Here we present the construction of the software, the results of the feasibility/satisfaction study with a descriptive analysis. Utility and discussion The database contains data of 2558 patients of which for 1702, a tumor bank exists (66.54%). The average treatment start period was April 2015 (ranging from December 1967 to November 2022; 118 patients were treated before 2012 and registered retrospectively when seen in long-term foloow-up consultations or for another cancer since November 2021). When questioned about their satisfaction of the tool, all health care professionals were satisfied. Access to the patient interface is currently open to 124 former patients. This was initially offered to 30 former patients, older than 15 years, affected by the disease within the last 5 years, who agreed to test it. All patients were satisfied with the tool, with an interest to test it in the long-term. Some of them testified to a decrease in mental load, as this verbatim : "I feel lighter. I allow myself to forget, I know I will get a notification when the time comes." Conclusions Freely available to all users, LOG-after enables (1) help with suggesting a personalized survivorship care plan for middle or long-term follow-up, (2) link with general practitioner, (3) empowerment of the patient, (5) an export of health data for analysis. Database URL for presentation: https://youtu.be/2Ga64iausJE

Background In sub-Saharan Africa, administration of hepatitis B virus (HBV) birth-dose vaccines remains suboptimal. Evidence is scarce on whether African countries should focus on increasing vaccine coverage or developing strategies incorporating additional measures, such as peripartum antiviral prophylaxis to pregnant women at high risk. To better inform decision makers, we estimated the residual risk of mother-to-child transmission despite HBV birth- dose vaccine in Cameroon. Methods We did a single-centre, longitudinal observational study. Pregnant women were systematically screened for HBV surface antigen (HBsAg) at Tokombere District Hospital (Tokombere district, Cameroon). Children born to HBsAg-positive mothers in 2009-16 who received the HBV birth-dose vaccine and three subsequent doses of pentavalent vaccine at 6, 10, and 14 weeks were followed up prospectively in 2015-17. In children, capillary blood was obtained for HBsAg rapid test and dried blood spots to quantify HBV DNA concentrations. Venous blood was also collected from HBsAg-positive children. Mother-to-child transmission was confirmed by whole-genome sequencing. Findings Between Jan 31, 2009, and Dec 31, 2016, 22 243 (66.8%) of 33 309 pregnant women accepted antenatal HBV screening, of whom 3901 (17.5%) were HBsAg positive. 2004 (51.4%) of 3901 children who were born to HBsAg-positive mothers received the HBV birth-dose vaccine, of whom 1800 (89.8%) also completed the three-dose pentavalent vaccine. In total, the current analysis included 607 children who had a follow-up serosurvey. The prevalence of HBsAg was 5.6% in children who received the birth-dose vaccine in less than 24 h, 7.0% in those who received it 24-47 h after birth, and 16.7% in those who received it 48-96 h after birth (p trend=0.083). 35 (89.7%) of 39 infected children were born to mothers positive for HBV e antigen with high HBV DNA of 5.3 log 10 IU/mL or more. Whole-genome sequencing of HBV in infected mother-child pairs confirmed high identity proportions of 99.97-100%. Interpretation We documented a substantial risk of mother-to-child transmission despite timely administration of the HBV birth-dose vaccine within 24 h after birth. To reach WHO's elimination targets, peripartum antiviral prophylaxis might be required in parts of Africa, in addition to increasing coverage of the HBV birth-dose vaccine. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd.

Objectives: Hepatitis B and D infections are highly endemic in Mauritania, with prevalences ranging from 10 to 20%. With the present prospective transversal pilot study, we aimed to evaluate the prevalences of HBV, HCV, and HDV infections in healthcare workers (HCWs), and offer treatment or vaccination as required. Methods: At inclusion, each HCW was screened for anti-HBc Ab (followed by HBsAg assay when positive). Additional biological analyses were performed for HBsAg + cases. Depending on the results, HBV vaccination or anti-viral treatment was offered. Results: A total of 3,857 HCWs were included, of whom 1,363 tested negative for anti-HBc Ab and received full vaccination. Of the 2,494 HCWs who were positive for anti-HBc Ab, 1,246 were positive for anti-HBs Ab and 418 were positive for HBsAg. Three HCWs were positive for HBeAg; 66 and 18 had HBV DNA levels respectively > 2,000 and > 20,000 IU/mL; and 48 were positive for anti-HDV Ab among whom 10 were positive for HDV RNA. HCV prevalence was 0.5%. Only seven HCWs fulfilled the criteria for treatment and five of them were treated. Conclusion: Few HCWs in Mauritania are immunised against HBV. The prevalences of anti-HBc Ab and HBsAg observed in this work were similar to those observed in our earlier works, whereas prevalence of active HDV infection was less high. HBV and HDV infections are a serious health concern in Mauritania. New recommendations developed in accordance with WHO guidelines should include mandatory HBV screening and immunisation for HCWs. (C) 2021 Elsevier Ltd. All rights reserved.

Objectives: In France, cervical cancer screening is based on human papillomavirus (HPV) testing on cervical samples (women aged 30-65) and cytological examination of Pap smears (25-29), but screening coverage is unsatisfactory. The CapU3 study aimed to propose urinary HPV testing on 13,535 women aged 35 to 65 who had not had a Pap smear since 2010. Methods: High-risk HPV (HR-HPV) detection was performed using a real-time PCR (Anyplex II HPV 28 Detection, Seegene (R)). Women with HR-HPV positive results were encouraged to have a cervical smear as soon as possible to detect the presence of cervical lesions. Results: The participation rate was 15.4%. Out of the 1,915 analyzed specimens, 1,711 and 190 were negative and positive, respectively, for at least 1 HR-HPV genotype. HR-HPV genotypes other than HPV-16 or HPV-18 were mostly detected as HPV-53 (23.7%) and HPV-68 (14.2%). A satisfactory gynecological follow-up was observed for HPV-positive women (92.1%). 23 abnormal smears were observed and eight high-grade cytological lesions after colposcopy and biopsy were diagnosed. Conclusions: As home HPV urinary testing is non-invasive and does not require medical attention, this method may be an alternative for women who are reluctant to have a Pap smear and thus extend screening coverage. (C) 2020 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Background The emergence of new strains in RNA viruses is mainly due to mutations or intra and inter-genotype homologous recombination. Non-homologous recombinations may be deleterious and are rarely detected. In previous studies, we identified HCV-1b strains bearing two tandemly repeated V3 regions in the NS5A gene without ORF disruption. This polymorphism may be associated with an unfavorable course of liver disease and possibly involved in liver carcinogenesis. Here we aimed at characterizing the origin of these mutant strains and identifying the evolutionary mechanism on which the V3 duplication relies. Methods Direct sequencing of the entire NS5A and E1 genes was performed on 27 mutant strains. Quasispecies analyses in consecutive samples were also performed by cloning and sequencing the NS5A gene for all mutant and wild strains. We analyzed the mutant and wild-type sequence polymorphisms using Bayesian methods to infer the evolutionary history of and the molecular mechanism leading to the duplication-like event. Results Quasispecies were entirely composed of exclusively mutant or wild-type strains respectively. Mutant quasispecies were found to have been present since contamination and had persisted for at least 10 years. This V3 duplication-like event appears to have resulted from non-homologous recombination between HCV-1b wild-type strains around 100 years ago. The association between increased liver disease severity and these HCV-1b mutants may explain their persistence in chronically infected patients. Conclusions These results emphasize the possible consequences of non-homologous recombination in the emergence and severity of new viral diseases.

The impact of basal core promoter (BCP) and precore (PC) mutants of the hepatitis B virus (HBV) on liver disease severity remains controversial. The aim of the present study was to screen BCP and PC mutations in 252 HBV surface antigen (HBsAg) positive carriers in France and to assess relationships between these mutations and severe fibrosis.

Background: Hepatitis C virus non-structural protein 5A is known to play a role in development of hepatocellular carcinoma (HCC) via interactions with host cell pathways.Objectives: Hepatitis C virus genotype lb strains presenting a wide insertion of 31 amino acids in the non-structural protein 5A V3 domain (V3 DI) were studied to determine whether this V3-like additional domain (V3 DII) was associated with HCC occurrence.Study design: Seventy-four patients' sera were screened for V3 DII presence regarding clinical status.Results: Three strains with duplicated V3 were detected among patients with progression to HCC (n=28), two strains among patients with liver cirrhosis (Ci, n=27) and none among patients with chronic hepatitis (Chr, n=19). Phylogenetic trees built from V3 DI and V3 DII sequences indicated that the latter clustered separately. In between-group clonal analysis, V3 DII sequences from the HCC group were found to be more distant from HCV-J than V3 DI sequences (p<0.0001). Between-group comparisons showed significant differences in genetic distances from HCV-J, in HCC V3 DI and HCC V3 DII compared to Ci V3 DI and Ci V3 DII sequences (p<0.0001). HCC V3 DII domain and its junction with V3 DI exhibited higher Shannon entropy values and enrichment in disorder-promoting residues.Conclusions: Taken together, our results suggest that V3 DII evolution may differ in strains associated with HCC occurrence. The presence of an intrinsically "disordered" V3 duplicate may alter the NS5A protein network. Further investigations are necessary to elucidate the potential impact of V3 duplication in the context of carcinogenesis. (C) 2015 Elsevier B.V. All rights reserved.

To investigate the impact of epoetin beta (EPO) on sustained virological response (SVR) in hepatitis C virus (HCV)-infected patients treated with peginterferon-ribavirin (RBV). Controlled, randomized, pragmatic multicenter study to assess 2 strategies, ie, the use (EPO group) or nonuse (control group) of EPO in terms of achieving SVR in treatment-naive, genotype non-2/non-3 HCV-infected patients receiving a 48-week treatment regimen of pegylated interferon α-2a (peg-IFN) plus RBV (randomization 2:1). The single-nucleotide polymorphisms of interferon lambda 3 (IFNL3) (rs12979860 and rs8099917), interferon lambda 4 (IFNL4) (ss469415590), and inosine triphosphatase (ITPA) (rs1127354 and rs7270101) were determined retrospectively. Two hundred twenty-seven patients were included in the study. In the global population (n = 227), the overall SVR rate was 52% (118/227). Nonresponse and relapse occurred in respectively 46/227 (20.3%) and 42/227 (18.5%) patients. In the intention-to-treat analysis, 55.5% of patients with anemia (n = 164) had a SVR, specifically 57.4% in the EPO group versus 52.4% in the control group, but the difference was not statistically significant. In the anemic population, independent factors associated with SVR were IFNL3 and IFNL4 polymorphisms, pretreatment HCV RNA level, iron level, and aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio. EPO has little impact on SVR in patients treated with peg-IFN+RBV and should be recommended only for patients with severe anemia.

Objectives: Mauritania is a highly endemic region for hepatitis B (HBV) and delta (HDV) viruses. No data are available on HDV's impact on the severity of liver disease in consecutive HBV-infected patients in Africa. This study evaluated the degree of liver fibrosis in a cohort of chronic HBV carriers.Methods: Three-hundred consecutive HBV-infected Mauritanian patients were checked for HDV infection via the detection of anti-HDV antibodies (Ab) and viral RNA. HBV-vs. HBV/HDV-infected patients were compared by physical examination, biological analyses, and the APRI (aspartate aminotransferase to platelet ratio index) and FibroMeter tests for determination of liver fibrosis.Results: More than 30% of the patients had anti-HDVAb. Among these, 62.2% were HDV-RNA positive. Co-infected patients were older (> 8-years) than HBV-mono-infected patients. They had more liver tests abnormalities and clinical or ultrasound signs of liver fibrosis. APRI and FibroMeter scores were also significantly increased in these patients. In multivariate analysis, beyond HDVAb, male gender and HBV-VL > 3.7 log IU/mL were the only markers linked to significant liver fibrosis.Conclusions: In Mauritania, HDV co-infection worsens liver disease, both clinically and biologically, as confirmed by the APRI and FibroMeter tests. These tests may be useful for the management of delta hepatitis, which is a major health problem in Mauritania. (C) 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

No recent data are available on hepatitis B virus (HBV) and hepatitis Delta virus (HDV) prevalence in Mauritania. One thousand twenty pregnant women and 946 patients visiting for routine checkups were screened for HBV and HDV infection. Demographic, epidemiological, ethnic, clinical, and biological data were recorded. HBV and HDV genotypes were determined by sequencing and phylogenetic analyses. In the pregnant women and patients cohorts, respectively, the prevalence of HBsAg (10.7% and 18.3%) and anti-HBcAb (66.3% and 76.5%) indicated high HBV endemicity. In pregnant women, exposure to HBV was significantly associated in multivariate analysis with education level, ethnicity, blood transfusion, and occupation. HDV antibodies (HDVAb) were found in 14.7% of pregnant women. In patients, HBsAg was found less frequently in females than in males. Again in multivariate analysis, exposure to HBV was significantly correlated with gender (males), and HDVAb positivity with age and gender. The HBV DNA viral load was >3?log?IU/ml in only 10.1% of pregnant women and in 17.3% of patients. HDV-RNA was detectable in 21 (67.7%) of the 31 patients positive for HDVAb, and in 11 of the 16 pregnant women positive for HDVAb (68.8%). The most frequent HBV genotypes were: HBV/D, 53%; HBV/E, 35%; and HBV/A, 12%. Sub-genotyping revealed HBV/D1,/D7, and the recently described/D8. HDV genotypes were: HDV-1, 90.3% and HDV-5, 9.7%. This study confirms the high prevalence of HBV and HDV infections in Mauritania and demonstrates the high genetic diversity of HBV in this country. J. Med. Virol. 84: 11861198, 2012. (C) 2012 Wiley Periodicals, Inc.

Background Osteopontin (OPN) plays an important role in the progression of chronic liver diseases. We aimed to quantify the liver, adipose tissue and serum levels of OPN in heavy alcohol drinkers and to compare them with the histological severity of hepatic inflammation and fibrosis. Methodology/Principal Findings OPN was evaluated in the serum of a retrospective and prospective group of 109 and 95 heavy alcohol drinkers, respectively, in the liver of 34 patients from the retrospective group, and in the liver and adipose tissue from an additional group of 38 heavy alcohol drinkers. Serum levels of OPN increased slightly with hepatic inflammation and progressively with the severity of hepatic fibrosis. Hepatic OPN expression correlated with hepatic inflammation, fibrosis, TGFβ expression, neutrophils accumulation and with the serum OPN level. Interestingly, adipose tissue OPN expression also correlated with hepatic fibrosis even after 7 days of alcohol abstinence. The elevated serum OPN level was an independent risk factor in estimating significant (F≥2) fibrosis in a model combining alkaline phosphatase, albumin, hemoglobin, OPN and FibroMeter® levels. OPN had an area under the receiving operator curve that estimated significant fibrosis of 0.89 and 0.88 in the retrospective and prospective groups, respectively. OPN, Hyaluronate (AUROC: 0.88), total Cytokeratin 18 (AUROC: 0.83) and FibroMeter® (AUROC: 0.90) estimated significance to the same extent in the retrospective group. Finally, the serum OPN levels also correlated with hepatic fibrosis and estimated significant (F≥2) fibrosis in 86 patients with chronic hepatitis C, which suggested that its elevated level could be a general response to chronic liver injury. Conclusion/Significance OPN increased in the liver, adipose tissue and serum with liver fibrosis in alcoholic patients. Further, OPN is a new relevant biomarker for significant liver fibrosis. OPN could thus be an important actor in the pathogenesis of this chronic liver disease.

Background: We compared three hyaluronic acid (HA) assays and analyzed the impact of their variations on FibroMeter scores.Methods: In a test group of 165 patients. HA levels were assessed with the commonly used ELISA assay from Corgenix, a new ELISA assay from Teco and an immunoturbidimetry assay from Wako, this latter tested across three different instruments. Five different FibroMeter scores were calculated.Results: Correlation across the three assays (r(s) between 0.969 and 0.995) was very good. Means of differences (d) were lower when the immunoturbidimetry assay was compared on different instruments: d between -3.4 and 2.0 mu g/L However, a higher value for HA measurement was observed with Corgenix assay, compared to the other two assays (Teco and Wako): d between 27.1 and 36.4 mu g/L. The assessment also demonstrated that HA variations had very little impact on FibroMeter scores: 0.0117 for virus and 0.0416 for alcoholic fibrosis scores, and between 0.58 and 1.71 for the area of fibrosis (expressed in percentage).Conclusions: The two new assays found lower values of HA, as compared to the Corgenix assay. However, these differences had very little impact on FibroMeter scores and had no impact on clinical evaluation of liver fibrosis. (C) 2010 Elsevier B.V. All rights reserved.

BACKGROUND & AIMS:We compared 5 non-specific and 2 specific blood tests for liver fibrosis in HCV/HIV co-infection. METHODS:Four hundred and sixty-seven patients were included into derivation (n=183) or validation (n=284) populations. Within these populations, the diagnostic target, significant fibrosis (Metavir F > or = 2), was found in 66% and 72% of the patients, respectively. Two new fibrosis tests, FibroMeter HICV and HICV test, were constructed in the derivation population. RESULTS:Unadjusted AUROCs in the derivation population were: APRI: 0.716, Fib-4: 0.722, Fibrotest: 0.778, Hepascore: 0.779, FibroMeter: 0.783, HICV test: 0.822, FibroMeter HICV: 0.828. AUROCs adjusted on classification and distribution of fibrosis stages in a reference population showed similar values in both populations. FibroMeter, FibroMeter HICV and HICV test had the highest correct classification rates in F0/1 and F3/4 (which account for high predictive values): 77-79% vs. 70-72% in the other tests (p=0.002). Reliable individual diagnosis based on predictive values > or = 90% distinguished three test categories: poorly reliable: Fib-4 (2.4% of patients), APRI (8.9%); moderately reliable: Fibrotest (25.4%), FibroMeter (26.6%), Hepascore (30.2%); acceptably reliable: HICV test (40.2%), FibroMeter HICV (45.6%) (p<10(-3) between tests). FibroMeter HICV classified all patients into four reliable diagnosis intervals (< or =F1, F1+/-1, > or =F1, > or =F2) with an overall accuracy of 93% vs. 79% (p<10(-3)) for a binary diagnosis of significant fibrosis. CONCLUSIONS:Tests designed for HCV infections are less effective in HIV/HCV infections. A specific test, like FibroMeter HICV, was the most interesting test for diagnostic accuracy, correct classification profile, and a reliable diagnosis. With reliable diagnosis intervals, liver biopsy can therefore be avoided in all patients.