Gaining Greater Insight into HCV Emergence in HIV-Infected Men Who Have Sex with Men: The HEPAIG Study

OBJECTIVES: The HEPAIG study was conducted to better understand Hepatitis C virus (HCV) transmission among human immuno-deficiency (HIV)-infected men who have sex with men (MSM) and assess incidence of HCV infection among this population in France. METHODS AND RESULTS: Acute HCV infection defined by anti-HCV or HCV ribonucleic acid (RNA) positivity within one year of documented anti-HCV negativity was notified among HIV-infected MSM followed up in HIV/AIDS clinics from a nationwide sampling frame. HIV and HCV infection characteristics, HCV potential exposures and sexual behaviour were collected by the physicians and via self-administered questionnaires. Phylogenetic analysis of the HCV-NS5B region was conducted. HCV incidence was 48/10 000 [95% Confidence Interval (CI):43-54] and 36/10 000 [95% CI: 30-42] in 2006 and 2007, respectively. Among the 80 men enrolled (median age: 40 years), 55% were HIV-diagnosed before 2000, 56% had at least one sexually transmitted infection in the year before HCV diagnosis; 55% were HCV-infected with genotype 4 (15 men in one 4d-cluster), 32.5% with genotype 1 (three 1a-clusters); five men were HCV re-infected; in the six-month preceding HCV diagnosis, 92% reported having casual sexual partners sought online (75.5%) and at sex venues (79%), unprotected anal sex (90%) and fisting (65%); using recreational drugs (62%) and bleeding during sex (55%). CONCLUSIONS: This study emphasizes the role of multiple unprotected sexual practices and recreational drugs use during sex in the HCV emergence in HIV-infected MSM. It becomes essential to adapt prevention strategies and inform HIV-infected MSM with recent acute HCV infection on risk of re-infection and on risk-reduction strategies

Tumor-Associated Macrophages (TAMs) Form an Interconnected Cellular Supportive Network in Anaplastic Thyroid Carcinoma

BACKGROUND: A relationship between the increased density of tumor-associated macrophages (TAMs) and decreased survival was recently reported in thyroid cancer patients. Among these tumors, anaplastic thyroid cancer (ATC) is one of the most aggressive solid tumors in humans. TAMs (type M2) have been recognized as promoting tumor growth. The purpose of our study was to analyze with immunohistochemistry the presence of TAMs in a series of 27 ATC. METHODOLOGY/PRINCIPAL FINDINGS: Several macrophages markers such as NADPH oxidase complex NOX2-p22phox, CD163 and CD 68 were used. Immunostainings showed that TAMs represent more than 50% of nucleated cells in all ATCs. Moreover, these markers allowed the identification of elongated thin ramified cytoplasmic extensions, bestowing a "microglia-like" appearance on these cells which we termed "Ramified TAMs" (RTAMs). In contrast, cancer cells were totally negative. Cellular stroma was highly simplified since apart from cancer cells and blood vessels, RTAMs were the only other cellular component. RTAMs were evenly distributed and intermingled with cancer cells, and were in direct contact with other RTAMs via their ramifications. Moreover, RTAMs displayed strong immunostaining for connexin Cx43. Long chains of interconnected RTAMs arose from perivascular clusters and were dispersed within the tumor parenchyma. When expressed, the glucose transporter Glut1 was found in RTAMs and blood vessels, but rarely in cancer cells. CONCLUSION: ATCs display a very dense network of interconnected RTAMs in direct contact with intermingled cancer cells. To our knowledge this is the first time that such a network is described in a malignant tumor. This network was found in all our studied cases and appeared specific to ATC, since it was not found in differentiated thyroid cancers specimens. Taken together, these results suggest that RTAMs network is directly related to the aggressiveness of the disease via metabolic and trophic functions which remain to be determined

Syndromic Surveillance of Acute Liver Failure in Emergency Departments (France, 2010-2012)

Our objectives were to explore the relevance of emergency departments' (ED) data, collected daily through the French syndromic surveillance system (414 EDs, 65% attendances), to describe the characteristics of patients with acute liver failure (ALF). Data corresponding to ICD10 codes related to hepatitis diagnosis that include ALF ICD10 code (K720) were extracted and analyzed. During 2010-2012, 246 730 attendances with hepatitis were recorded of which 2 475 (1%) were linked to ALF. Patients with ALF were male (60%), their median age was 55 years. This study shows the relevance of French syndromic surveillance data to assess the burden of ALF

Hepatitis C virus genotype 3 and the risk of severe liver disease in a large population of drug users in France

International audienceAlthough risk factors for cirrhosis in chronic hepatitis C virus (HCV) infection have been identified, the role of HCV-genotype 3 remains controversial, and limited data are available in drug users. The aim of the study was to assess risk factors for severe liver disease (cirrhosis/hepatocellular carcinoma) in HCV-infected drug users between 2001 and 2007 in France. Patients who reported drug use and who had been referred for HCV infection to hepatology centres from a national surveillance system were identified. The severity of liver disease was assessed clinically and histologically (Metavir score). Factors associated with sever liver disease were analysed after estimating missing values by multiple imputation. Of the 4065 drug users naive to anti-HCV treatment who were referred to the 26 participating centres, 8.0% had severe liver disease, 25.7% were infected with HCV-genotype 3. Factors associated independently with an increased risk of severe liver disease were HCV-genotype 3 (adjusted odds ratio, multiple imputation, (aORMI) = 1.6, [95%CI: 1.2-2.1]), HIV infection (aORMI = 1.8, [1.2-2.8]), male sex (aORMI = 2.0, [1.4-2.8]), age over 40 years (aORMI = 2.1, [1.6-2.9]), history of excessive alcohol consumption (aORMI = 2.8, [2.1-3.7]) and duration of infection ≥18years (aORMI = 2.9, [2.0-4.3]). This analysis shows that HCV-genotype 3 is associated with severe liver disease in drug users, independently of age, sex, duration of infection, alcohol consumption and co-infection with HIV. These results are in favour of earlier treatment for drug users infected with HCV-genotype 3 and confirm the need for concomitant care for excessive alcohol consumption

An Automated Surveillance System (SurCeGGID) for the French Sexually Transmitted Infection Clinics: Epidemiological Monitoring Study

BackgroundViral and bacterial sexually transmitted infections (STIs) are public health concerns worldwide, but surveillance systems are not comprehensive enough to design and monitor accurately STI control strategies in most countries. In 2016, 320 STI clinics (CeGIDDs in French) were implemented in France, primarily targeting most exposed populations, although access is free of charge for anybody. ObjectiveThis article describes the mandatory surveillance system (SurCeGIDD) based on CeGIDD’s individual data aiming to better guide STI prevention. MethodsA decree ensured the use of software to manage consultations in CeGIDDs and to transfer surveillance data. A web service was implemented to secure data transfer from CeGIDDs’ software to a centralized database. CeGIDDs can also transfer data in CSV format via a secured data-sharing platform. Then, data are automatically checked before integration. Data on sociodemographic variables, sexual exposure, blood exposure, symptoms, STI tests, STI diagnoses, and sexual health services delivery were collected for the previous year (n–1). Preliminary and descriptive analyses of 2017-2018 data transmitted in 2018 and 2019, respectively, were performed using numbers and proportions for qualitative variables. ResultsIn 2017, 54/320 (16.9%) CeGIDDs transmitted their data. In 2018, this number of participants increased to 143/320 (44.7%) CeGIDDs. The corresponding volume of records increased from 2414 in 2017 to 382,890 in 2018. In 2018, most attendances were hospital based (263,480/382,890, 68.81%). In 2018, attendees were mostly men 227,326/379,921 (59.84%), while 151,963/379,921 (40%) were women 632/379,921 (0.17%) transgenders. The median age was 27 years for men, 23 years for women, and 30 years for transgender. Half of the attendees (81,964/174,932, 46.85%) were heterosexual men, 69,016/174,932 (39.45%) heterosexual women, 20,764/174,932 (11.87%) men who have sex with men, and 3188/174,932 (1.82%) women who have sex with women. A majority of them were born in France (227,698/286,289, 79.53%) and unemployed 115,913/211,707 (54.75%). The positivity rates were 0.37% for 205,348 HIV serologies, 1.31% for 131,551 hepatitis B virus serologies, 7.16% for 161,241 Chlamydia trachomatis PCR, 2.83% for 146,649 gonorrhea PCR, 1.04% for the syphilis combination of treponema and nontreponema serologies, and 5.96% for 13,313 Mycoplasma genitalium PCR. ConclusionsDespite challenges, the effectiveness of the SurCeGIDD surveillance based on routine patients’ records was demonstrated. The wide range of information, including socioeconomic determinants, might help to better guide and evaluate the prevention policies and services delivery. However, the growing volumes of information will require adapted tools and algorithms for the data management and analyses

Clinical and virological features of chronic hepatitis B in the French national surveillance program, 2008–2012: A cross-sectional study

Background & Aims: Among people living with HBV, only a subset of individuals with chronic hepatitis is in need of treatment, and this proportion varies according to the population, region, and setting. No estimates of the proportion of people who are infected with HBV and meet the treatment eligibility criteria in France are available. Methods: 552 treatment-naïve individuals with chronic HBV infection referred for the first time to a hepatology reference centre between 2008 and 2012 were prospectively included. Demographic, clinical, and laboratory data were analysed. Results: In total, 61.1% of patients were males, with a median age of 37.5 years. Moreover, 64% were born in an intermediate- or high-HBV endemicity country, and 90% were HBeAg-negative. At referral, median HBV DNA and HBsAg levels were 3.3 and 3.6 log IU/ml, respectively; 37.8% of patients had alanine aminotransferase >40 U/L, and 29.0% had moderate or severe fibrosis (≥F2), including 9.4% with cirrhosis. The most prevalent genotypes were D (34.7%), E (27.4%), and A (25.7%). Coinfections were rare: 2.4% were HIV-positive, 4.0% were HCV-positive, and 6.0% were HDV-positive. According to the 2017 EASL Clinical Practice Guidelines, using a single time point analysis, 2.7% of patients were classified as HBeAg-positive chronic infection, 6.1% as HBeAg-positive chronic hepatitis B, 26.5% as HBeAg-negative chronic hepatitis B, and 61.1% as HBeAg-negative chronic infection, whereas 3.6% patients could not be classified. The performance of HBsAg level quantification to identify individuals with HBeAg-negative chronic hepatitis B was poor. A total of 29.1% met the criteria for initiation of antiviral treatment, whereas 66.5% remained under routine clinical surveillance. Most eligible patients initiated recommended first-line therapies, including tenofovir (45.3%), entecavir (36.8%), or pegylated interferon alpha (11.6%). Conclusions: Of all cases, 9.4% had cirrhosis at presentation and 29.1% met the 2017 EASL Clinical Practice Guidelines treatment criteria. HBsAg levels failed to accurately identify individuals with HBeAg-negative chronic infection. Lay summary: Among French adults chronically infected with HBV referred for the first time to hepatology reference centres, about one-third had a significant liver disease. Approximately one-third of individuals met criteria for initiation of antiviral treatment based on entecavir or tenofovir or, occasionally, pegylated interferon alpha

French hepatitis C care cascade: substantial impact of direct-acting antivirals, but the road to elimination is still long

International audienceBackground: Hepatitis C virus (HCV) elimination by 2030, as targeted by the World Health Organization (WHO), requires that 90% of people with chronic infection be diagnosed and 80% treated. We estimated the cascade of care (CoC) for chronic HCV infection in mainland France in 2011 and 2016, before and after the introduction of direct-acting antivirals (DAAs). Methods: The numbers of people (1) with chronic HCV infection, (2) aware of their infection, (3) receiving care for HCV and (4) on antiviral treatment, were estimated for 2011 and 2016. Estimates for 1) and 2) were based on modelling studies for 2011 and on a virological sub-study nested in a national cross-sectional survey among the general population for 2016. Estimates for 3) and 4) were made using the National Health Data System. Results: Between 2011 and 2016, the number of people with chronic HCV infection decreased by 31%, from 192,700 (95% Credibility interval: 150,900-246,100) to 133,500 (95% Confidence interval: 56,900-312,600). The proportion of people aware of their infection rose from 57.7 to 80.6%. The number of people receiving care for HCV increased by 22.5% (representing 25.7% of those infected in 2016), while the number of people on treatment increased by 24.6% (representing 12.1% of those infected in 2016). Conclusions: This study suggests that DAAs substantially impact CoC. However, access to care and treatment for infected people remained insufficient in 2016. Updating CoC estimates will help to assess the impact of new measures implemented since 2016 as part of the goal to eliminate HCV

Primary resistance of hepatitis B virus to nucleoside and nucleotide analogues

International audienc

Hépatite B chronique prise en charge dans les pôles de référence depuis 2008 : premiers résultats

www.invs. sante.fr/behweb/2010/01/r-1.htmNational audienceLa surveillance nationale de l'hépatite B chronique a été mise en place en 2008, en collaboration avec les pôles de ré- férence (services hospitalo-universitaires d'hépatologie), pour décrire les caractéristiques épidémiologiques et clinico- biologiques des patients nouvellement pris en charge pour une hépatite B chronique. L'hépatite B chronique est définie par le portage de l'antigène HBs (AgHBs) depuis plus de six mois. Les caractéristiques des patients qui sont recueillies incluent les modalités de découverte de l'AgHBs et leurs expositions à risque vis-à-vis du virus de l'hépatite B (VHB). Nous présentons certaines caractéristiques des patients naïfs de traitement antiviral, selon le niveau de prévalence de l'AgHBs du pays de naissance (endémicité faible vs. moyenne/forte). Entre janvier 2008 et août 2009, 1 016 patients ont été pris en charge, dont 78% sont nés dans une zone de moyenne ou forte endémicité VHB. La découverte de l'AgHBs est fortuite pour 69% des patients. Le délai entre le dépistage et la prise en charge, déterminé pour 837 patients, est supérieur à trois ans pour 41% des patients nés en zone de faible endémicité et pour 22% de ceux nés ailleurs. Ces résultats préliminaires suggèrent des pratiques de dépistage de l'AgHBs imparfaites et un retard à la prise en charge des personnes dépistées, en particulier celles nées dans une zone de faible endémicité VHB