Impact of hepatitis B and delta virus co-infection on liver disease in Mauritania: a cross sectional study.

OBJECTIVES: Mauritania is a highly endemic region for hepatitis B (HBV) and delta (HDV) viruses. No data are available on HDV\u27s 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

Prevalence, risk factors, and molecular epidemiology of hepatitis B and hepatitis delta virus in pregnant women and in patients in Mauritania

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

DNA replication stress response involving PLK1, CDC6, POLQ, RAD51 and CLASPIN upregulation prognoses the outcome of early/mid-stage non-small cell lung cancer patients

International audienceLung cancer is the leading cause of cancer deaths worldwide. Clinical staging classification is generally insufficient to providea reliable prognosis, particularly for early stages. In addition, prognostic factors are therefore needed to better forecast lifeexpectancy and optimize adjuvant therapeutic strategy. Recent evidence indicates that alterations of the DNA replication programcontribute to neoplasia from its early stages and that cancer cells are frequently exposed to endogenous replication stress.We therefore hypothesized that genes involved in the replication stress response may represent an under-explored source ofbiomarkers. Expressions of 77 DNA replication-associated genes implicated in different aspects of chromosomal DNA replication,including licensing, firing of origins, elongation, replication fork maintenance and recovery, lesion bypass and post-replicative repairwere determined in primary tumors and adjacent normal tissues from 93 patients suffering from early- or mid-stage non-small celllung cancer (NSCLC). We then investigated a statistically significant interaction between gene expressions and survival of early-stage NSCLC patients.The expression of five genes, that is,POLQ, PLK1, RAD51, CLASPINandCDC6was associated with overall,disease-free and relapse-free survival. The expression levels are independent of treatment and stage classification. ExceptRAD51,their prognostic role on survival persists after adjustment on age, sex, treatment, stage classification and conventional proliferationmarkers, with a hazard ratio of 36.3 forPOLQ(95%CI 2.6–517.4,P¼0.008), 23.5 forPLK1(95%CI 1.9–288.4,P¼0.01), 20.7 forCLASPIN(95%CI 1.5–275.9,P¼0.02) and 18.5 forCDC6(95%CI 1.3–267.4,P¼0.03). We also show that a five-gene signature includingPOLQ,PLK1, RAD51, CLASPINandCDC6separates patients into low- and high-risk groups, with a hazard ratio of 14.3 (95% CI 5.1–40.3,Po0.001). This ‘replication stress’ metamarker may be a reliable predictor of survival for NSCLC, and may also help understand themolecular mechanisms underlying tumor progression

Bridge The Distance Between Breast Pathologists: When The Senopath Network Opens Up To The Telepathology

Introduction/ Background In clinical practice, pathologists commonly face breast lesions, which are difficult to diagnose and which re- quire discussion. In Midi-Pyrénées, the largest region ofFrance, this problem has led us to develop in 2011 a peer group for breast diseases entitled SENOPATH. Aims In order to reduce second opinion delay, erase geographical barrier and provide continuing education, we aimed to introduce an effective online and outline telepathology system in the SENOPATH network. Methods A case review by SENOPATH can be requested by any pathologist in the Midi-Pyrénées region, by filling a form through the ONCOMIP network (organization dedicated to oncology in the Midi- Pyrénées region). The slides are sent for digitalization at The University Cancer Institute - Oncopole, using a Hamamatsu 2.0-RS scanner (until 2014) and a 3DHISTECH Pannoramic 250 scanner, then anonymized and transferred to a shared storage space at Toulouse Paul Sabatier University. Virtual slides can be seen before and/or after the meeting by members of the group by login in the online 3DHISTECHCaseCentervia the Imag’IN platform website. The group, who meets on a monthly basis, has recently developed a synchronized webinar  (using 3DHISTECH Case Center and Pannoramic Viewer) coupled with a conference call in order to ease the attendance of pathologists from remote pathology laboratories. A consensual diagnosis and final pathology report are issued for each case and sent to the referent clinician via the patient medical file securely hosted by ONCOMIP. Results From January 2012 to December 2015, 211 cases (39 in 2012, 50 in 2013, 75 in 2014 and 47 in 2015) have been reviewed during 43 meetings. Ten out of 43 meetings (23%) used telepathology. Sixty-one cases out of 211 (29%) were actually digitalized, mainly using theHamamatsu2.0-RS scanner. In average, the number of attending pathologists was9 to 10from 2012 to 2015. The average number of cases reviewed per meeting was 3 in 2012 and 5 between 2013 and 2015. Two main motives for review were identified: diagnostic ‘routine difficulty’ (equivocal or discordant cases, invasive vs in situ lesion, atypical vs malignant lesions, immunohistochemistry scoring pitfalls) or rare tumours. The rare tumour category included among others syringomatous tumour of the nipple, low-grade adenosquamous, myoepithelial, mucoepidermoid or secretory carcinomas, adenomyoepithelioma, atypical microglandular adenosis, sclerosing papillary hyperplasia without myoepithelium and periductal stromal tumour. Molecular analyses requested by the group and implemented in the diagnosis process mainly included immunohistochemistry and fluorescence in situ hybridization (HER2, ETV6, MAML2, MYB). The SENOPATH network committee review for difficult or rare lesions of the breast has considerably improved the pathologist’s network in our region. This working group is regularly requested by oncologists to solve difficult cases. Our aims for the next few years are 1/ to digitalize all of the cases reviewed by the SENOPATH network, 2/ to use telepathology facilities provided by the Imag’IN platform in order to widen the group to a national level, and 3/ to construct a growing online library of virtual slides for breast challenging lesions.