Socioeconomic Deprivation Weighs Heavily on Liver Fibrosis and Mortality After Hepatitis C Cure (ANRS CO22 Hepather).

Although Hepatitis C virus (HCV) infection can be cured with direct-acting antivirals (DAA), some cured patients face a serious risk of advanced liver damage and early mortality. In order to avoid these two negative health outcomes, it is important to identify and assess related risk factors. Little is currently known about socioeconomic and behavioural factors in this context. Using data from the ANRS CO22 Hepather cohort, we tested for associations between socioeconomic and behavioural factors and (i) advanced liver fibrosis (defined as an FIB-4 > 3.25) assessed longitudinally using a mixed-effects logistic regression model (both the whole population and stratified on advanced liver fibrosis status at the time of HCV cure) and (ii) all-cause mortality (Cox proportional hazards model), during post-HCV cure follow-up. Among 5833 participants cured of HCV, living in poverty was associated with postcure advanced liver fibrosis in participants without this diagnosis at the time of HCV cure (population attributable fraction-PAF-of 8.6%) and with mortality in the whole study population (PAF of 10.6%). The detrimental effects of unhealthy alcohol use and heavy tobacco smoking, as well as the beneficial effect of living with a stable partner were also highlighted. We highlighted the major role of poverty and behavioural factors in advanced liver fibrosis and all-cause mortality in patients cured of HCV. Encouraging linkage to social support services and healthy behaviours after successful DAA treatment could limit morbidity and increase survival in this population. Clinical Trial Registration: ClinicalTrials.gov: NCT01953458.

A novel community-based therapeutic education program for reducing alcohol-related harms and stigma in people with alcohol use disorders: A quasi-experimental study (ETHER study).

INTRODUCTION: Alcohol use disorder (AUD) is associated with a significant disease burden in France, where alcohol use is deeply rooted in culture. However, the treatment gap is large because of several barriers, including stigmatisation and drinkers' apprehension about total abstinence. However, standardised and evidence-based interventions based on controlled-drinking for people with AUD are lacking. We aimed to assess the effectiveness of a novel community-based French therapeutic patient education (TPE) program for people with AUD named Choizitaconso. METHODS: A before-after non-randomised quasi-experimental study, named ETHER, was designed and implemented with people living with AUD, over a period of 6 months. The primary outcome was percentage change in the number of alcohol-related harms experienced. Secondary outcomes were percentage changes in psycho-social patient-reported and community-validated outcomes. Participants in the intervention group (n = 34) benefited from the 10-week TPE program Choizitaconso, while the comparison group (n = 58) received standard care. The Kruskall-Wallis and chi-squared or Fisher's exact tests were used to compare before-after changes in variables in both groups. Linear regression models were used to test for the effect of study group on each outcome and to test for the effect of alcohol consumption as a confounder. RESULTS: At 6 months, all outcomes but one either remained stable or numerically improved in both groups. Internalised stigma significantly improved in the intervention group (p = 0.026) but not in the comparison group (p = 0.207), with a significant group effect (p = 0.014). DISCUSSION AND CONCLUSIONS: This study demonstrates the effectiveness of the Choizitaconso TPE program on community-validated outcomes, especially internalised stigma.

Adherence to opioid agonist therapy predicts uptake of direct-acting antivirals in people who use drugs: results from the French national healthcare database (the ANRS FANTASIO study).

BACKGROUND: Opioid agonist therapy (OAT) is associated with reduced injection, reduced HCV transmission, and more opportunities to initiate hepatitis C virus (HCV) treatment in people who use drugs (PWUD). We aimed to study the extent to which adherence to OAT was predictive of increased uptake of direct-acting antivirals (DAA) in PWUD with chronic HCV infection. METHODS: Using the French national healthcare system database, we targeted PWUD (i.e. with a history of OAT) who had chronic HCV infection and were eligible for DAA during 2014-2016. Adherence to OAT was computed as a time-varying variable expressing the proportion of days covered by OAT receipt, over any six-month interval before DAA receipt. We used a Cox proportional hazards model to estimate the association between adherence to OAT and the rate of DAA uptake after adjustment for age, sex, alcohol use disorder, socioeconomic status, and liver disease severity. RESULTS: Among the 22,615 persons included in the ANRS FANTASIO study, 3438 (15.2%) initiated DAA during the study period. After multivariable adjustment, adherence to OAT was associated with a higher rate of DAA initiation. However, this association was not linear, and only individuals on OAT for 20% or more of the time in the previous six-month period had a higher rate of DAA initiation (adjusted hazard ratio [95% confidence interval]: 1.28 [1.18-1.38]). Other variables associated with DAA initiation were male sex, older age, cirrhosis or liver cancer, and higher socioeconomic status. CONCLUSIONS: Adherence to OAT is a major predictor of DAA initiation in PWUD living with chronic HCV infection in France. Our results also suggest that even moderate adherence to OAT can facilitate DAA uptake. Adequate HCV training for OAT prescribers together with interventions to ensure adherence to OAT will help improve DAA initiation rates and reach HCV elimination goals.

Severe liver fibrosis in the HCV cure era: Major effects of social vulnerability, diabetes, and unhealthy behaviors.

Background & Aims: After HCV cure, not all patients achieve significant liver fibrosis regression. We explored the effects of clinical and socio-behavioral factors on liver fibrosis, before and after HCV cure with direct-acting antivirals. Methods: We analyzed data from the ongoing ANRS CO22 HEPATHER cohort, which prospectively collects clinical and socio-behavioral data on HCV-infected patients. Mixed-effects logistic regression models helped identify predictors of longitudinal measures of severe liver fibrosis, defined as a fibrosis-4 index >3.25. We also estimated the adjusted population attributable fractions (PAFs) for modifiable risk factors. Results: Among the 9,692 study patients (accounting for 24,687 visits over 4 years of follow-up, 48.5% of which were post-HCV cure), 26% had severe fibrosis at enrolment. After multivariable adjustment, HCV-cured patients had an 87% lower risk of severe fibrosis. An inverse dose-response relationship was found for coffee consumption, with the risk of severe fibrosis diminishing by 58% per additional cup/day (adjusted odds ratio (aOR 0.42; 95% CI 0.38-0.46). Unemployment, low educational level, and diabetes were associated with a higher severe fibrosis risk (aOR 1.69; 95% CI 1.32-2.16, aOR 1.50; 95% CI 1.20-1.86, and aOR 4.27; 95% CI 3.15-5.77, respectively). Severe fibrosis risk was 3.6/4.6-fold higher in individuals with previous/current unhealthy alcohol use than in abstinent patients. All these associations remained valid after HCV cure. The risk factors accounting for the greatest severe fibrosis burden were unemployment, low education level, and diabetes (PAFs: 29%, 21%, and 17%, respectively). Conclusions: Monitoring liver fibrosis after HCV cure is crucial for patients with low socioeconomic status, previous/current unhealthy alcohol use, and diabetes. Innovative HCV care models for the most socially vulnerable individuals and interventions for healthier lifestyles are needed to reinforce the positive effects of HCV cure on liver health. Lay summary: After hepatitis C virus (HCV) cure, not all patients achieve significant liver fibrosis regression. Herein, we studied the effects of clinical and socio-behavioral factors on the risk of severe liver fibrosis. Coffee consumption was strongly inversely associated with severe fibrosis, while diabetes, previous and current unhealthy alcohol use were associated with a 4.3-, 3.6- and 4.6-fold higher risk of severe fibrosis, respectively. Unemployment and low educational level were also associated with a higher risk of severe fibrosis. All these associations remained valid after HCV cure. These results demonstrate the need to continue liver fibrosis monitoring in at-risk groups, and to facilitate healthier lifestyles after HCV cure as a clinical and public health priority.

Incidence of cervical, breast and colorectal cancers between 2010 and 2015 in people living with HIV in France.

BACKGROUND: We aimed to evaluate the incidence rates between 2010 and 2015 for invasive cervical cancer (ICC), breast cancer (BC), and colorectal cancer (CRC) in people living with HIV (PLWH) in France, and to compare them with those in the French general population. These cancers are targeted by the national cancer-screening program. SETTING: This is a retrospective study based on the longitudinal data of the French Dat'AIDS cohort. METHODS: Standardized incidence ratios (SIR) for ICC and BC, and incidence rates for all three cancers were calculated overall and for specific sub-populations according to nadir CD4 cell count, HIV transmission category, HIV diagnosis period, and HCV coinfection. RESULTS: The 2010-2015 CRC incidence rate was 25.0 [95% confidence interval (CI): 18.6-33.4] per 100,000 person-years, in 44,642 PLWH (both men and women). Compared with the general population, the ICC incidence rate was significantly higher in HIV-infected women both overall (SIR = 1.93, 95% CI: 1.18-3.14) and in the following sub-populations: nadir CD4 ≤ 200 cells/mm3 (SIR = 2.62, 95% CI: 1.45-4.74), HIV transmission through intravenous drug use (SIR = 5.14, 95% CI: 1.93-13.70), HCV coinfection (SIR = 3.52, 95% CI: 1.47-8.47) and HIV diagnosis before 2000 (SIR = 2.06, 95% CI: 1.07-3.97). Conversely, the BC incidence rate was significantly lower in the study sample than in the general population (SIR = 0.56, 95% CI: 0.42-0.73). CONCLUSION: The present study showed no significant linear trend between 2010 and 2015 in the incidence rates of the three cancers explored in the PLWH study sample. Specific recommendations for ICC screening are still required for HIV-infected women and should focus on sub-populations at greatest risk.

Metabolic Disorders in Patients with Chronic Hepatitis B Virus Infection: Coffee as a Panacea? (ANRS CO22 Hepather Cohort).

People living with chronic hepatitis B virus (HBV) infection are at high risk of liver disease progression, which is positively associated with metabolic disorders, but inversely associated with dyslipidemia. Diet, including dietary antioxidants, is a lever of metabolic disorder management. In particular, elevated coffee consumption is associated with different metabolic outcomes in the general population. We aimed to test whether such associations occur in HBV-infected people. Based on cross-sectional data from the ANRS CO22 Hepather cohort, we performed logistic regression models with (i) dyslipidemia, (ii) hypertension, and (iii) diabetes as outcomes, and with demographic, clinical, and socio-behavioral (including coffee consumption) data as explanatory variables. Among 4746 HBV-infected patients, drinking ≥3 cups of coffee per day was associated with a higher risk of dyslipidemia (adjusted odds ratio [95% confidence interval] 1.49 [1.10-2.00], p = 0.009) and a lower risk of hypertension (0.64 [0.50-0.82], p = 0.001). It was not associated with diabetes. Elevated coffee consumption was associated with a higher risk of dyslipidemia and a lower risk of hypertension in HBV-infected patients, two effects expected to be associated with favorable clinical outcomes. Further studies should test whether such metabolic benefits translate into reduced mortality risk in this population.

Elevated coffee consumption is associated with a lower risk of elevated liver fibrosis biomarkers in patients treated for chronic hepatitis B (ANRS CO22 Hepather cohort).

BACKGROUND AND AIMS: Patients chronically infected with hepatitis B virus (HBV) are at high risk of liver fibrosis, cirrhosis and liver cancer, despite recent therapeutic advances. It is therefore crucial to find non-pharmaceutical options for liver fibrosis prevention in this population. Using cross-sectional data from the ANRS CO22 Hepather cohort, we aimed to identify socio-demographic and modifiable risk factors for significant fibrosis in chronic HBV patients. METHODS: Logistic regression or Firth's penalized maximum likelihood logistic regression (according to outcome prevalence) multivariable models were used to test for associations between explanatory variables and significant fibrosis, as assessed by three non-invasive markers: aspartate aminotransferase to platelet ratio index (APRI), FIB-4, and gamma glutamyltransferase to platelet ratio (GPR). Analyses were stratified by HBV treatment status. RESULTS: The study population comprised 2065 untreated and 1727 treated chronic HBV patients. Elevated coffee consumption was consistently associated with a lower risk of elevated fibrosis biomarkers in all three treated-participant models, suggesting a dose-response relationship (adjusted odds ratios for ≥3 cups/day versus 0 cups/day: 0.16, 0.35 and 0.62, p ≤ 0.002, according to APRI, FIB-4 and GPR, respectively). Other modifiable risk factors included tobacco and alcohol use. CONCLUSION: Elevated coffee consumption was consistently associated with a lower risk of significant liver fibrosis, as assessed by three non-invasive markers in treated chronic HBV patients. This result can be immediately used in real-world situations, as increasing coffee consumption may be beneficial for patients at risk of advanced liver disease.

Knowledge of liver fibrosis stage among adults with NAFLD/NASH improves adherence to lifestyle changes.

BACKGROUND & AIMS: Though lifestyle interventions can reverse disease progression in people with non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH), unawareness about disease severity might compromise behavioural changes. Data from this first international cross-sectional survey of individuals with NAFLD/NASH were used to identify correlates of both unawareness about fibrosis stage and its association with adherence to lifestyle adjustments. METHODS: Adults with NAFLD/NASH registered on the platform Carenity were invited to participate in an online 20-min, six-section survey in Canada, France, Germany, Italy, Spain and the United Kingdom to describe their experience with NAFLD/NASH and its care (N = 1411). Weighted binary and multinomial logistic regressions were performed to estimate the effect of explanatory variables on unawareness of fibrosis stage and poor adherence to lifestyle changes respectively. RESULTS: In the study group, 15.5% had obesity and 59.2% did not know their fibrosis stage. After multiple adjustments, individuals with a body mass index (BMI) ≥35 were over twice as likely to not know their fibrosis stage. People with a BMI >30 had a threefold higher risk of having poor adherence to lifestyle changes. Unawareness about fibrosis stage was also significantly associated with poor adherence to lifestyle adjustments. CONCLUSIONS: As fibrosis stage is becoming the main predictor of NAFLD progression, improving patient-provider communication-especially for people with obesity-about liver fibrosis stage, its associated risks and how to mitigate them, is needed. Training for healthcare professionals and promoting patient educational programmes to support behaviour changes should also be included in the liver health agenda.

Mindfulness as a Protective Factor Against Increased Tobacco and Alcohol Use in Hospital Workers Following the First COVID-19-Related Lockdown: a Study in Southern France.

COVID-19-related national lockdowns worldwide have had repercussions on people's well-being and have led to increased substance use. Mindfulness has previously been associated with reduced psychological distress and benefits in terms of addictive behaviors. We aimed to assess whether dispositional mindfulness protected against increased tobacco and alcohol use in hospital workers after France's first lockdown started. All workers in two French hospitals were contacted by email to participate in an online survey. Three hundred eighty-five workers answered. We ran two separate logistic regression models to test for associations between the level of dispositional mindfulness and both increased tobacco and alcohol use, after adjusting for affect deterioration. Dispositional mindfulness was associated with a lower likelihood of increased tobacco (adjusted odds ratio (AOR) [95% CI] 0.71 [0.51; 0.99], p = 0.046) and alcohol (0.66 [0.50; 0.87], p = 0.004) use. The effect of mindfulness on tobacco use was partially mediated by affect deterioration. Dispositional mindfulness appeared to be a protective factor against lockdown-related tobacco and alcohol use increases in French hospital workers.

Cannabis Use Is Inversely Associated with Overweight and Obesity in Hepatitis B Virus-Infected Patients (ANRS CO22 Hepather Cohort).

Background: Chronic hepatitis B virus (HBV) infection may evolve into cirrhosis and hepatocellular carcinoma, and this progression may be accelerated by specific risk factors, including overweight and obesity. Although evidence for a protective effect of cannabis use on elevated body weight has been found for other populations, no data are available for HBV-infected patients. Aims: We aimed to identify risk factors (including cannabis use) for overweight and obesity in patients with HBV chronic infection. Methods: Using baseline data from the French ANRS CO22 Hepather cohort, we performed two separate analyses, one using "central obesity" (based on waist circumference) and the other "overweight" and "obesity" (based on body mass index) as outcomes. Logistic and multinomial regressions were used to model central obesity and overweight/obesity, respectively. Results: Among the 3706 patients in the study population, 50.8% had central obesity, 34.7% overweight, and 14.4% obesity. After multivariable adjustment, current cannabis use was associated with a 59% lower risk of central obesity compared with no lifetime use (adjusted odds ratio [95% CI]: 0.41 [0.24 to 0.70]). It was also associated with a 54% and 84% lower risk of overweight (adjusted relative risk ratio [95% CI]: 0.46 [0.27 to 0.76]) and obesity (0.16 [0.04 to 0.67]), respectively. Conclusions: Cannabis use was associated with lower risks of overweight and obesity in patients with HBV chronic infection. Future studies should test whether these potential benefits of cannabis and cannabinoid use translate into reduced liver disease progression in this high-risk population.

Examining the Relationships between Mindfulness and Tobacco Craving Factors.

BACKGROUND: Relationships between mindfulness and general craving have been documented. However, there is still no data regarding relationships between mindfulness and the different craving factors. METHODS: Using data from an online survey among hospital workers smoking tobacco in France (n = 127), we performed linear regression models with the four craving factors as outcomes, and dispositional mindfulness as explanatory variable. RESULTS: After adjusting for nicotine dependence, mindfulness was negatively associated with general craving and three out of four craving factors (emotionality, compulsivity and purposefulness, but not expectancy). CONCLUSIONS: These results support the implementation of mindfulness-based interventions in the context of tobacco cessation attempt.

HCV Cure and Cannabis Abstinence Facilitate Tobacco Smoking Quit Attempts in HIV-HCV Co-Infected Patients (ANRS CO13 HEPAVIH Cohort Study).

In Western countries, tobacco smoking is highly prevalent among patients co-infected with HIV and hepatitis C virus (HCV). In the era of antiretrovirals and HCV cure, smoking-related health damages contribute greatly to morbidity and mortality in HIV-HCV co-infected patients. We used longitudinal data from the ANRS CO13 HEPAVIH cohort to identify the correlates of tobacco smoking quit attempts (TSQA) in HIV-HCV co-infected patients. TSQA were modelled using a multivariable discrete-time Cox proportional hazards model in 695 HIV-HCV co-infected tobacco smokers. HCV cure was associated with a 76% higher chance of TSQA (adjusted hazard ratio [95% confidence interval]: 1.76 [1.06-2.93], p = 0.029), and cannabis use with a 37% lower chance (0.63 [0.40-1.00], p = 0.049), independently of the mode of HIV transmission, other psychoactive substance use, and body mass index. Patients should be screened for tobacco and cannabis use at HCV treatment initiation and during follow-up. They should also be provided with comprehensive counselling and referral to addiction services. Non-smoking routes of cannabis administration should be promoted for cannabis users who wish to quit smoking tobacco.

Cannabis use is associated with a lower risk of diabetes in chronic hepatitis C-infected patients (ANRS CO22 Hepather cohort).

Chronic hepatitis C virus (HCV) infection is a risk factor of insulin resistance, and HCV-infected patients are at a high risk of developing diabetes. In the general population, research has shown the potential benefit of cannabis use for the prevention of diabetes and related metabolic disorders. We aimed to test whether cannabis use is associated with a lower risk of diabetes in chronic HCV-infected patients. Chronic HCV-infected patients (n = 10 445) were selected from the French national, multicenter, observational ANRS CO22 Hepather cohort. Cross-sectional data collected at cohort enrollment were used to assess the association between patients' clinical and behavioural characteristics and the risk of diabetes. Logistic regression model was performed with cannabis use as the main independent variable and a significance level set at 5%. A similar model stratified by the presence of advanced liver fibrosis (FIB-4 > 3.25) was also run. After multivariable adjustment, current (AOR [95%CI]: 0.49 [0.38-0.63]) and former (0.81 [0.67-0.98], P < .001) cannabis use were both associated with a reduced odds of diabetes. Conversely, male gender, tobacco use, elevated BMI, poverty, being a migrant and advanced fibrosis were associated with increased odds of diabetes. The association between cannabis use and diabetes was maintained in the stratified analysis. In this large cross-sectional study of chronic HCV-infected patients, cannabis use was associated with a lower risk of diabetes independently of clinical and socio-behavioural factors. Further studies are needed to elucidate a potential causal link and shed light on cannabis compounds and mechanisms involved in this relationship.

HCV-Related Mortality Among HIV/HCV Co-infected Patients: The Importance of Behaviors in the HCV Cure Era (ANRS CO13 HEPAVIH Cohort).

Mortality among individuals co-infected with HIV and hepatitis C virus (HCV) is relatively high. We evaluated the association between psychoactive substance use and both HCV and non-HCV mortality in HIV/HCV co-infected patients in France, using Fine and Gray's competing-risk model adjusted for socio-demographic, clinical predictors and confounding factors, while accounting for competing causes of death. Over a 5-year median follow-up period, 77 deaths occurred among 1028 patients. Regular/daily cannabis use, elevated coffee intake, and not currently smoking were independently associated with reduced HCV-mortality (adjusted sub-hazard ratio [95% CI] 0.28 [0.10-0.83], 0.38 [0.15-0.95], and 0.28 [0.10-0.79], respectively). Obesity and severe thinness were associated with increased HCV-mortality (2.44 [1.00-5.93] and 7.25 [2.22-23.6] versus normal weight, respectively). Regular binge drinking was associated with increased non-HCV-mortality (2.19 [1.10-4.37]). Further research is needed to understand the causal mechanisms involved. People living with HIV/HCV co-infection should be referred for tobacco, alcohol and weight control interventions and potential benefits of cannabis-based therapies investigated.

Elevated Fatty Liver Index as a Risk Factor for All-Cause Mortality in Human Immunodeficiency Virus-Hepatitis C Virus-Coinfected Patients (ANRS CO13 HEPAVIH Cohort Study).

BACKGROUND AND AIMS: Human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected patients are at high risk of metabolic complications and liver-related events, which are both associated with hepatic steatosis and its progressive form, nonalcoholic steatohepatitis, a known risk factor for mortality. The fatty liver index (FLI), a noninvasive steatosis biomarker, has recently drawn attention for its clinical prognostic value, although its capacity to predict mortality risk in HIV-HCV-coinfected patients has never been investigated. Using a Cox proportional hazards model for mortality from all causes, with data from the French National Agency for Research on Aids and Viral Hepatitis CO13 HEPAVIH cohort (983 patients, 4,432 visits), we tested whether elevated FLI (≥60) was associated with all-cause mortality. APPROACH AND RESULTS: After multiple adjustment, individuals with FLI ≥ 60 had almost double the risk of all-cause mortality (adjusted hazard ratio [95% confidence interval], 1.91 [1.17-3.12], P = 0.009), independently of the following factors: HCV cure (0.21 [0.07-0.61], P = 0.004), advanced fibrosis (1.77 [1.00-3.14], P = 0.05), history of hepatocellular carcinoma and/or liver transplantation (7.74 [3.82-15.69], P < 10-3 ), history of indirect clinical signs of cirrhosis (2.80 [1.22-6.41], P = 0.015), and HIV Centers for Disease Control and Prevention clinical stage C (2.88 [1.74-4.79], P < 10-3 ). CONCLUSIONS: An elevated FLI (≥60) is a risk factor for all-cause mortality in HIV-HCV-coinfected patients independently of liver fibrosis and HCV cure. In the present era of nearly 100% HCV cure rates thanks to direct-acting antivirals, these findings encourage the more systematic use of noninvasive steatosis biomarkers to help identify coinfected patients with higher mortality risk.

Sleep disturbances in HIV-HCV coinfected patients: indications for clinical management in the HCV cure era (ANRS CO13 HEPAVIH cohort).

OBJECTIVES: Although common among patients coinfected with HIV and hepatitis C virus (HCV), sleep disturbances (SD) are still poorly documented in this population in the HCV cure era. This longitudinal study aimed at analysing SD in HIV-HCV coinfected patients and identifying their clinical and sociobehavioural correlates. METHODS: We used 5-year annual follow-up data from 1047 participants in the French National Agency for Research on Aids and Viral Hepatitis Cohort 13 'Hépatite et VIH' (ANRS CO13 HEPAVIH) cohort of HIV-HCV coinfected patients to identify clinical (medical records) and behavioural (self-administered questionnaires) correlates of SD (mixed-effects logistic regression). SD were identified using one item documenting the occurrence of insomnia or difficulty falling asleep (ANRS 'Action Coordonnée 24' self-reported symptoms checklist), and two items documenting perceived sleep quality (Center for Epidemiologic Studies Depression and WHO Quality of Life HIV-specific brief scales). RESULTS: Seven hundred and sixteen (68.4%) patients with completed self-administered questionnaires reported SD at their most recent follow-up visit. In the multivariable model, hazardous alcohol consumption (Alcohol Use Disorders Identification Test-Consumption score ≥ 4 for men, ≥ 3 for women) (adjusted odds ratio = 1.61; 95% confidence interval: 1.09-2.36), depressive symptoms (6.78; 4.36-10.55) and the number of other physical and psychological self-reported symptoms (1.10; 1.07-1.13) were associated independently with SD after adjustment for sex, age and employment status. HCV cure was not associated significantly with SD. CONCLUSION: SD remain frequent in HIV-HCV coinfected patients and are associated with a series of modifiable behavioural risk factors. Independent of HCV cure, improved screening and comprehensive management of alcohol use, physical and psychological self-reported symptoms and depression are essential in this population. Closer investigation of these risk factors of SDs may both increase sleep quality and indirectly improve patients' clinical outcomes.

Clinical Features and Complications of Coxiella burnetii Infections From the French National Reference Center for Q Fever.

Importance: Q fever remains widespread throughout the world; the disease is serious and causes outbreaks and deaths when complications are not detected. The diagnosis of Q fever requires the demonstration of the presence of Coxiella burnetii and the identification of an organic lesion. Objective: To describe the hitherto neglected clinical characteristics of Q fever and identifying risk factors for complications and death. Design, Setting, and Participants: This prospective cohort study conducted from January 1, 1991, through December 31, 2016, included patients treated at the French National Reference Center for Q fever with serologic findings positive for C burnetii and clinical data consistent with C burnetii infection. Clinical data were prospectively collected by telephone. Patients with unavailable clinical data or an unidentified infectious focus were excluded. Main Outcomes and Measures: Q fever complications and mortality. Results: Of the 180 483 patients undergoing testing, 2918 had positive findings for C burnetii and 2434 (68.8% men) presented with clinical data consistent with a C burnetii infection. Mean (SD) age was 51.8 (17.4) years, and the ratio of men to women was 2.2. At the time of inclusion, 1806 patients presented with acute Q fever, including 138 with acute Q fever that progressed to persistent C burnetii infection, and 766 had persistent focalized C burnetii infection. Rare and hitherto neglected foci of infections included lymphadenitis (97 [4.0%]), acute Q fever endocarditis (50 [2.1%]), hemophagocytic syndrome (9 [0.4%]), and alithiasic cholecystitis (11 [0.4%]). Vascular infection (hazard ratio [HR], 3.1; 95% CI, 1.7-5.7; P < .001) and endocarditis (HR, 2.4; 95% CI, 1.1-5.1; P = .02) were associated with an increased risk of death. Independent indicators of lymphoma were lymphadenitis (HR, 77.4; 95% CI, 21.2-281.8; P < .001) and hemophagocytic syndrome (HR, 19.1; 95% CI, 3.4-108.6; P < .001). The presence of anticardiolipin antibodies during acute Q fever has been associated with several complications, including hepatitis, cholecystitis, endocarditis, thrombosis, hemophagocytic syndrome, meningitis, and progression to persistent endocarditis. Conclusions and Relevance: Previously neglected foci of C burnetii infection include the lymphatic system (ie, bone marrow, lymphadenitis) with a risk of lymphoma. Cardiovascular infections were the main fatal complications, highlighting the importance of routine screening for valvular heart disease and vascular anomalies during acute Q fever. Routine screening for anticardiolopin antibodies during acute Q fever can help prevent complications. Positron emission tomographic scanning could be proposed for all patients with suspected persistent focused infection to rapidly diagnose vascular and lymphatic infections associated with death and lymphoma, respectively.