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Background Whether aminosalicylates or thiopurines reduce the risk of colorectal cancer ( CRC) in inflammatory bowel ( IBD) disease is controversial. Aim To assess simultaneously the chemopreventive effect of aminosalicylates or thiopurines in a case-control study nested in the CESAME observational cohort that enrolled consecutive patients with IBD between May 2004 and June 2005. Patients were followed up to December 2007. Methods Study population comprised 144 case patients who developed CRC from the diagnosis of IBD (65 and 79 cases diagnosed, respectively, before and from 2004, starting year of the prospective observational period of CESAME) and 286 controls matched for gender, age, IBD subtype and year of diagnosis, and cumulative extent of colitis. Exposure to aminosalicylates or thiopurines was defined by an exposure to the treatment during the year of the diagnosis of cancer. The propensity of receiving 5- ASA and thiopurines was quantified by a composite score taking into account patient and IBD characteristics. The role of aminosalicylates or thiopurines was assessed by multivariate analysis. Propensity scores and the history of primary sclerosing cholangitis were entered into the multivariate model for adjustment. Results By multivariate analysis adjusted for propensity, a significant protective effect of exposure to drugs during the year of cancer was found for aminosalicylates ( OR = 0.587, 95% CI: 0.367-0.937, P = 0.0257), but not for thiopurines ( OR = 0.762, 95% CI: 0.432-1.343, P = 0.3468). Conclusion In a case-control study nested in the CESAME cohort, a significant decrease in the risk of colorectal cancer in IBD was associated with exposure to aminosalicylates, not to thiopurines. [ABSTRACT FROM AUTHOR]

In hepatitis B 'e' antigen ( HBeAg) positive patients with hepatitis B virus ( HBV) mono-infection, intensification of nucleos(t)ide analogue treatment with pegylated interferon (Peg IFN) could help induce higher HBeAg seroclearance rates. Our aim was to determine the long-term effect of adding Peg IFN to tenofovir ( TDF)-containing antiretroviral therapy on seroclearance in HBeAg-positive patients co-infected with the human immunodeficiency virus ( HIV) and HBV. In this prospective matched cohort study, 46 patients with 1-year Peg IFN intensification during TDF-containing antiretroviral therapy ( TDF+Peg IFN) were matched 1:1 to controls undergoing TDF without Peg IFN ( TDF) using a time-dependent propensity score based on age, CD4+ count and liver cirrhosis status. Kinetics of HBeAg quantification ( qHBeAg) and hepatitis B surface antigen quantification ( qHBsAg) were estimated using mixed-effect linear regression and time to HBeAg seroclearance or HBsAg seroclearance was modelled using proportional hazards regression. At baseline, previous TDF exposure was a median 39.8 months ( IQR=21.4-59.4) and median qHBeAg and qHBsAg levels were 6.9 PEIU/ mL and 3.72 log10 IU/ mL, respectively ( P>.5 between groups). Median follow-up was 33.4 months ( IQR=19.0-36.3). During intensification, faster average declines of qHBeAg (−0.066 vs −0.027 PEIU/ mL/month, P=.001) and qHBsAg (−0.049 vs −0.026 log10 IU/ mL/month, P=.09) were observed in patients undergoing TDF+Peg IFN vs TDF, respectively. After intensification, qHBeAg and qHBsAg decline was no different between groups ( P=.7 and P=.9, respectively). Overall, no differences were observed in HBeAg seroclearance ( TDF+Peg IFN=13.2 vs TDF=12.6/100 person·years, P=.5) or HBsAg seroclearance rates ( TDF+Peg IFN=1.8 vs TDF=1.3/100 person·years, P=.7). In conclusion, Peg IFN intensification in HBeAg-positive co-infected patients did not lead to increased rates of HBeAg or HBsAg clearance, despite faster declines of antigen levels while on PegIFN. [ABSTRACT FROM AUTHOR]

Background The risk of urinary tract cancers, including kidney and bladder cancers, was increased in transplant recipients receiving thiopurines. Aim To assess the risk of urinary tract cancers in patients with inflammatory bowel disease (IBD) receiving thiopurines in the CESAME observational cohort. Methods Between May 2004 and June 2005, 19 486 patients with IBD, 30.1% of whom were receiving thiopurines, were enrolled. Median follow-up was 35 months (IQR: 29-40). Results Ten and six patients developed respectively kidney and bladder cancer. The incidence rates of urinary tract cancer were 0.48/1000 patient-years in patients receiving thiopurines (95% CI: 0.21-0.95), 0.10/1000 patient-years in patients who discontinued thiopurines (95% CI: 0.00-0.56) and 0.30/1000 patient-years in patients never treated with thiopurines (95% CI: 0.12-0.62) at entry. The standardised incidence ratio of urinary tract cancer was 3.40 (95% CI: 1.47-6.71, P = 0.006) in patients receiving thiopurines, 0.64 (95% CI: 0.01-3.56, P = 0.92) in patients previously exposed to thiopurines and 1.17 (95% CI: 0.47-12.42, P = 0.78) in patients never treated with thiopurines. The multivariate-adjusted hazard ratio (HR) of urinary tract cancer between patients receiving thiopurines and those not receiving thiopurines was 2.82 (95% CI: 1.04-7.68, P = 0.04). Other significant risk factors were male gender (HR: 3.98, 95% CI: 1.12-14.10, P = 0.03) and increasing age (HR after 65 years (ref <50): 13.26, 95% CI: 3.52-50.03, P = 0.0001). Conclusion Patients with IBD receiving thiopurines have an increased risk of urinary tract cancers. Clinically relevant excess risk is observed in older men. [ABSTRACT FROM AUTHOR]

In Egypt, as elsewhere, liver biopsy ( LB) remains the gold standard to assess liver fibrosis in chronic hepatitis C ( CHC) and is required to decide whether a treatment should be proposed. Many of its disadvantages have led to develop noninvasive methods to replace LB. These new methods should be evaluated in Egypt, where circulating virus genotype 4 ( G4), increased body mass index and co-infection with schistosomiasis may interfere with liver fibrosis assessment. Egyptian CHC-infected patients with G4 underwent a LB, an elastometry measurement ( Fibroscan©), and serum markers ( APRI, Fib4 and Fibrotest©). Patients had to have a LB ≥15 mm length or ≥10 portal tracts with two pathologists blinded readings to be included in the analysis. Patients with hepatitis B virus co-infection were excluded. Three hundred and twelve patients are reported. The performance of each technique for distinguishing F0 F1 vs F2 F3 F4 was compared. The area under receiver operating characteristic curves was 0.70, 0.76, 0.71 and 0.75 for APRI, Fib-4, Fibrotest© and Fibroscan©, respectively (no influence of schistosomiasis was noticed). An algorithm using the Fib4 for identifying patients with F2 stage or more reduced by nearly 90% the number of liver biopsies. Our results demonstrated that noninvasive techniques were feasible in Egypt, for CHC G4-infected patients. Because of its validity and its easiness to perform, we believe that Fib4 may be used to assess the F2 threshold, which decides whether treatment should be proposed or delayed. [ABSTRACT FROM AUTHOR]

Background Consequences of latent cytomegalovirus ( CMV) infection reactivation on inflammatory bowel disease ( IBD) flare, as a flare-worsening factor or simple bystander, are debated. Impact of anti-viral treatment on IBD course is poorly known. Aim To assess the impact of CMV reactivation on patients hospitalised for IBD flare and the effect of anti-viral treatment on IBD flare in patients with CMV reactivation. Methods First, a population of UC patients from Saint-Antoine hospital, in flare with positive blood CMV PCR without anti-viral treatment ( n = 26), were compared to matched patients with negative blood CMV PCR in a case-control study. Secondly, a total of 110 hospitalisations between October 2003 and May 2012 for IBD flare-up with CMV reactivation (80 diagnosed on blood PCR, 33 on tissue PCR) were identified in three French referral centres. Evolution following CMV reactivation diagnosis was compared between patients receiving anti-viral treatment and those who did not. Results In the case-control study, no differences were observed between the two groups regarding length of hospital stay and colectomy rate. Comparing treated and untreated patients, no differences were observed at inclusion regarding age, gender, IBD type, immunosuppressant, CRP and haemoglobin level. No differences were observed regarding CRP level decrease at 10 days and colectomy rate at 3 months. Anti-viral treatment was associated with lower serum albumin level at inclusion and longer hospitalisation. Conclusions CMV reactivation does not appear to alter the course of IBD flare. CMV treatment does not seem to impact the course of IBD. These results should be confirmed prospectively. [ABSTRACT FROM AUTHOR]

. Chronic hepatitis C is an independent risk factor for severe drug hepatotoxicity. Successful treatment of chronic hepatitis C may modulate drug hepatotoxicity, as it is associated with a decline in hepatic enzyme release and halts fibrosis progression in HIV/HCV-coinfected patients. The aim of this study was to determine biological and/or clinical determinants of alanine aminotransferase and/or aspartate aminotransferase elevation (>five-fold above the upper limit of normal in patients with normal baseline levels or >3.5-fold increase from baseline in those with increased baseline levels) in a large prospective cohort of HIV/HCV-coinfected patients on HAART who had previously been treated for HCV infection. Median follow-up exceeded five years. Cox proportional hazards models were used. At baseline, 248 patients had been receiving antiretroviral therapy for a mean of 6.3 (± 3.2) years. Seventy-one patients (29%) had a sustained HCV viral response (SVR). During follow-up, 66 patients (26.6%) received a second course of HCV therapy and 29 (44%) of them had an SVR. Severe transaminitis occurred in 64 patients (26%). In multivariate analysis, no SVR (HR 33.33, 95% CI 4.54-222, P = 0.001) and stavudine-based therapy (HR 2.11, 95% CI 1.12-3.99, P = 0.018) remained significantly associated with severe transaminitis. A SVR to anti-HCV therapy is thus associated with a markedly reduced risk of severe transaminitis during antiretroviral therapy. Treatment of HCV infection should therefore be a priority in HIV-coinfected patients. Stavudine is associated with an increased risk of severe transaminitis. [ABSTRACT FROM AUTHOR]

Background Surveillance colonoscopy is recommended for inflammatory bowel disease (IBD) patients with longstanding extensive colitis (LEC). Aims To assess modalities and results of colonoscopic surveillance in a subset of CESAME cohort patients at high risk of colorectal cancer (CRC) and followed in university French hospitals. Methods Among 910 eligible patients with more than a 7-year history of extensive colitis at CESAME enrolment, 685 patients completed a questionnaire on surveillance colonoscopy and 102 were excluded because of prior proctocolectomy. Finally, 583 patients provided information spanning a median period of 41 months (IQR 38-43) between cohort enrolment and the end of follow-up. Details of the colonoscopic procedures and histological findings were obtained for 440 colonoscopies in 270 patients. Results Only 54% (n = 312) of the patients with LEC had at least one surveillance colonoscopy during the study period, with marked variations across the nine participating centres (27% to 70%, P ⩽ 0.0001). Surveillance rate was significantly lower in Crohn's colitis than in ulcerative colitis (UC) (48% vs. 69%, P ⩽ 0.0001). Independent predictors of colonoscopic surveillance were male gender, UC IBD subtype, longer disease duration, previous history of CRC and disease management in a centre with large IBD population. Random biopsies, targeted biopsies and chromoendoscopy were performed during respectively 71%, 27 and 30% of surveillance colonoscopies. Two cases of high-grade dysplasia were detected in patients undergoing colonoscopic surveillance. Two advanced-stage CRC were diagnosed in patients who did not have colonosocopic surveillance. Conclusions Colonoscopic surveillance rate is low in IBD patients with longstanding extensive colitis. [ABSTRACT FROM AUTHOR]

Objective The frequency and significance of, and liver biopsy findings associated with, a persistently normal alanine aminotransferase (ALT) level in HIV/hepatitis C virus (HCV)-coinfected patients are poorly characterized. We analysed factors associated with persistently normal ALT levels, defined as at least three consecutive normal ALT values over a 6-month period, in a group of 381 HIV/HCV-coinfected patients. Methods Patients were categorized into two groups according to ALT values: group 1, patients with persistently normal ALT levels; and group 2, patients with elevated ALT values. Possible interactions with host factors, HIV and HCV viral factors, antiretroviral treatment and histological features were examined. Results Thirty-six patients (9.4%) had persistently normal ALT levels. None of the 36 patients had cirrhosis. Seven patients (19.4%) had a METAVIR fibrosis score of F3. In multivariate analysis, a lower mean METAVIR inflammation score [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.28–0.89; P=0.017], the absence of steatosis (OR 0.43, 95% CI 0.20–0.90; P=0.026) and HCV genotype 4 infection (OR 2.81, 95% CI 1.15–6.68; P=0.023) were associated with persistently normal ALT levels. Conclusion The slower progression of chronic hepatitis in patients with persistently normal ALT levels could be related, in part, to a lower frequency of steatosis [ABSTRACT FROM AUTHOR]

Background Insulin resistance (IR), the major feature of the metabolic syndrome, is also common in patients with chronic HCV infection. Liver fibrosis and steatosis are known potential outcome of chronic hepatitis B or C infection. Studies have shown that HIV positive individuals co-infected with HCV have more rapid live disease progression than those with HIV alone. Few data have reported the influence of IR on steatosis and fibrosis in the context of HIV-HCV coinfection. Aim To test the association among insulin resistance (IR), liver fibrosis and liver steatosis in HIV–HCV and HCV-infected patients. Patients and methods A total of 170 HIV–HCV-infected patients matched by age, gender and genotype with 170 HCV mono-infected patients were included. Patients were considered to be IR when the homeostasis model assessment of IR >2. Significant fibrosis was considered if METAVIR ≥F2 and significant steatosis if ≥10%. Results Insulin resistance was independently associated in HCV patients with fibrosis [odds ratio (OR) = 2.04 (95% CI 1.02–4)], a body mass index (BMI) >25 kg/m² [OR = 3.33 (1.47–7.69)] and steatosis [OR = 3.33 (1.67–6.67)]. Fibrosis ≥F2 was associated in HCV patients with high liver activity grade (≥A2) [OR = 8.33 (3.85–16.67)], male gender [OR = 3.03 (1.33–7.14)] and IR [OR = 2.44 (1.15–5)]. In HIV–HCV patients, ≥A2 [OR = 5.56 (1.64–20)] was associated with fibrosis. Steatosis ≥10% was associated in HCV patients with IR [OR = 3.13 (1.59–6.25) and ≥F2 (OR = 2.22 (1.15–4.17)]. In HIV–HCV, a BMI >25 kg/m² [OR = 3.85 (1.64–9.10)], ≥A2 [OR = 2.16 (1.02–4.55); P = 0.044] and nucleoside reverse transcriptase inhibitor [OR = 3.61 (1.19–10.96); P = 0.023] were independently associated with significant liver steatosis. Conclusions Insulin resistance is associated with liver fibrosis and steatosis in HCV mono-infected, but not in HIV–HCV co-infected patients. Significant liver fibrosis is associated with IR independent of liver steatosis only in HCV mono-infected patients. [ABSTRACT FROM AUTHOR]

Weight loss is reported by more than 20% of hepatitis C virus (HCV)-monoinfected patients treated with the peg-interferon (peg-IFN) and ribavirin combination. The aim of this study was to determine the incidence and risk factors of severe weight loss (≥10%) in human immunodeficiency virus (HIV) / HCV-coinfected patients participating in a randomized, controlled 48-week trial comparing peg-IFN alpha 2b plus ribavirin with IFN alpha-2b plus ribavirin. Univariate and multivariate analyses were used to identify links with antiretroviral treatments, anti-HCV therapy and clinical and laboratory findings. One hundred eleven (28.9%) of 383 patients who received at least one dose of anti-HCV treatment subsequently had severe weight loss. Among patients who took at least 80% of the planned total dose, severe weight loss occurred in 74 patients (32.7%). In multivariate analysis, age >40 years [hazard ratio (HR), 1.59; 95% CI 1.09 to 2.31; P = 0.016], body mass index (BMI) >22 (HR, 1.72; 95% CI, 1.16 to 2.55; P = 0.0069), peg-IFN alpha-2b (HR, 1.82; 95% CI, 1.24 to 2.69; P = 0.0022) and female sex (HR, 1.60; 95% CI, 1.05 to 2.43; P = 0.027) were associated with severe weight loss. In contrast, patients taking non-nucleoside reverse transcriptase inhibitors (NNRTI)-containing antiretroviral regimens were less likely to lose weight (HR, 0.62; 95% CI, 0.39 to 0.96; P = 0.034). Lipodystrophy tended to occur more frequently in patients who had severe weight loss than in the other patients (26.1% vs 17.6%; P = 0.0682) and patients whose weight loss >5% persisted 24 weeks after the completion of anti-HCV therapy ( n = 58 / 111) were more likely to be receiving stavudine-based antiretroviral therapy, suggesting that mitochondrial toxicity plays some role in weight loss. These findings show that severe weight loss is a frequent side effect of anti-HCV therapy in HIV / HCV-coinfected patients. The underlying mechanisms remain to be identified. [ABSTRACT FROM AUTHOR]

Background Since 1998, prestorage leucoreduction of all cellular blood components has been made mandatory in France. The French blood service needed to follow the data on the quality of the blood components prepared by blood centres. Material and Methods Quality control (QC) data were submitted to a central data bank by each blood centre. The data were stratified by preparation method for analysis of key performance criteria – residual white blood cell (WBC) and total haemoglobin content. The red blood cell (RBC) preparation processes and the methods for measuring haemoglobin content and residual WBC count were those routinely employed by blood centres. Each year, more than 15 500 RBCs were tested. Results Red blood cells had a mean haemoglobin content between 53·6 and 54·9 g/unit depending on the year (2001 to 2005). The requirement of 40 g/unit was reached for about 99% of units. The haemoglobin content was influenced by the preparation process: 56·8 ± 6·9 vs. 50·6 ± 5·6 g/unit in average for whole blood filtration or RBC filtration, respectively. Apheresis RBCs exhibited a reduced variability (51·8 ± 3·1 g/unit). The median residual WBC count remained low (0·046 to 0·057 × 106 WBCs/unit), and the percentage of RBC units exceeding the 1 × 106 WBCs/unit cut-off ranged from 1·5 to 0·6% depending on the year. A seasonal pattern was observed, with a significant increase ( P < 0·001) of the median residual WBC count and of the percent of non-conforming units during the summer months. Conclusion Our QC data suggest an overall compliance with the standard. Our data bank is useful to inform on the performance of leucoreduced RBC preparation processes carried out with market available devices. [ABSTRACT FROM AUTHOR]

The most frequent and the most troublesome adverse effect of interferon plus ribavirin-based therapy is anaemia. The aim of this analysis was to determine the incidence and risk factors of anaemia (Hb < 10 g/dL) in human immunodeficiency virus/hepatitis C virus (HCV)-coinfected patients receiving anti-HCV therapy. We reviewed all cases of anaemia occurring among 416 patients participating in a randomized, controlled 48-week trial comparing peginterferon (peg-IFN) alpha 2b plus ribavirin with interferon alpha-2b plus ribavirin. Univariate and multivariate analyses were used to identify links with antiretroviral treatments, HCV therapy and clinical and laboratory findings. Sixty-one (15.9%) of the 383 patients who received at least one dose of anti-HCV treatment developed anaemia. In multivariate analysis the risk of anaemia was significantly associated with zidovudine (OR, 3.27 95% CI, 1.64–6.54, P = 0.0008) and peg-IFN (OR, 2.35; 95% CI, 1.16–4.57, P = 0.0179). The risk of anaemia was lower in patients with higher baseline haemoglobin levels (OR, 0.35 95% CI, 0.26–0.49, P < 0.0001) and in patients receiving protease inhibitor-based antiretroviral therapy (OR, 0.51 95% CI, 0.30–0.86, P = 0.0114). Zidovudine discontinuation could help to avoid anaemia associated with anti-HCV therapy. [ABSTRACT FROM AUTHOR]

Twenty to 40% of hepatitis C virus (HCV)-infected patients do not have a recognized parenteral risk factor suggesting that still-unidentified modes of transmission exist. In order to investigate potential routes of HCV transmission for patients with no recognized parenteral risk factor, we conducted a multicentre case–control study. A total of 450 HCV-seropositive patients with no history of transfusion or intravenous drug use and 757 controls were recruited from the general population and matched for sex, age, geographical residence and number of chronic diseases. All subjects answered an interviewer-administered questionnaire on potential risk factors for HCV. Eighty per cent of cases had chronic hepatitis or cirrhosis. Respective percentages of genotypes 1, 2, 3, 4 and 5 were 65, 14, 11, 5 and 4. Among the 66 items considered, multivariate analysis identified 15 independent risk factors for HCV infection: nosocomial [admission to medical (odds ratio, OR = 2.1) or surgical ward (OR = 1.7), digestive endoscopy (OR = 1.9), abortion (OR = 1.7)], outpatient treatments [cutaneous ulcer and wound care (OR = 10.1), diathermy (OR = 3.0), gamma globulin (OR = 1.7), intravenous (OR = 1.7) or intramuscular (OR = 1.4) injections, varicose vein sclerotherapy (OR = 1.6), acupuncture (OR = 1.5)] and lifestyle-associated [intranasal cocaine use (OR = 4.5), practice of contact sports (OR = 2.3), beauty treatments (OR = 2.0), professional pedicure/manicure (OR = 1.7)]. These factors could explain 73% of community-acquired hepatitis C. In conclusion, for patients with unexplained routes of HCV infection, our data incriminate previously unidentified risk factors (abortions, some dermatological procedures, outpatient injections, contact sports, beauty treatments, professional pedicure/manicure) and confirm those already recognized (hospitalization, digestive endoscopy, acupuncture and intranasal cocaine use). [ABSTRACT FROM AUTHOR]

We propose a transmission model to estimate the main characteristics of influenza transmission in households. The model details the risks of infection in the household and in the community at the individual scale. Heterogeneity among subjects is investigated considering both individual susceptibility and infectiousness. The model was applied to a data set consisting of the follow-up of influenza symptoms in 334 households during 15 days after an index case visited a general practitioner with virologically confirmed influenza. Estimating the parameters of the transmission model was challenging because a large part of the infectious process was not observed: only the dates when new cases were detected were observed. For each case, the data were augmented with the unobserved dates of the start and the end of the infectious period. The transmission model was included in a 3-levels hierarchical structure: (i) the observation level ensured that the augmented data were consistent with the observed data, (ii) the transmission level described the underlying epidemic process, (iii) the prior level specified the distribution of the parameters. From a Bayesian perspective, the joint posterior distribution of model parameters and augmented data was explored by Markov chain Monte Carlo (MCMC) sampling. The mean duration of influenza infectious period was estimated at 3.8 days (95 per cent credible interval, 95 per cent CI [3.1,4.6]) with a standard deviation of 2.0 days (95 per cent CI [1.1,2.8]). The instantaneous risk of influenza transmission between an infective and a susceptible within a household was found to decrease with the size of the household, and established at 0.32 person day−1 (95 per cent CI [0.26,0.39]); the instantaneous risk of infection from the community was 0.0056day−1 (95 per cent CI [0.0029,0.0087]). Focusing on the differences in transmission between children (less than 15 years old) and adults, we estimated that the former were more likely to transmit than adults ( posterior probability larger than 99 per cent), but that the mean duration of the infectious period was similar in children (3.6 days, 95 per cent CI [2.3,5.2]) and adults (3.9 days, 95 per cent CI [3.2,4.9]). The posterior probability that children had a larger community risk was 76 per cent and the posterior probability that they were more susceptible than adults was 79 per cent. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background and Objectives Since 1 April 1998, all cellular blood components in France have been leucoreduced. The current French standard is < 1 × 10[sup 6] white blood cells (WBC) per unit with a 95% confidence that at least 97% of units will meet this standard. Materials and methods Quality control (QC) data for leucoreduced cellular blood components were collected from the 41 French blood centres over a 5-month period. Conformance to the standard was determined using a non-parametric approach. Results More than 98% of the 15 286 red cell concentrates and of the 2895 platelet concentrates tested had < 1 × 10[sup 6] WBC per unit. One filtration device gave unsatisfactory results and its use was discontinued. Conclusion This QC survey shows an overall compliance with the standard. The data illustrate the practical value of identifying devices or centres with consistent QC problems. [ABSTRACT FROM AUTHOR]

Background and Aims: The economic impact of managing patients with hepatitis C virus (HCV) infection remains unknown. This study aimed to assess the economic burden of chronic HCV infection from a national health insurance perspective and the impact of direct-acting antivirals (DAAs) using nationwide real-world data., Methods: Patients with chronic HCV infection were identified from the French Health Insurance Claims Databases (SNDS) and matched for age and sex to the general population. Health resource utilization and reimbursements were summarized according to healthcare expenditure items from 2012 to 2021. The economic burden attributable to chronic HCV infection was evaluated over a 10-year period. Finally, the impact of DAAs was estimated using economic data derived from the SNDS., Results: A total of 145 187 patients with chronic HCV infection were identified. Among the patients eligible for DAA therapy, 81.5% had received DAA by the end of 2021. Over a 10-year period, managing patients with chronic HCV infection resulted in an additional cost of €9.71 billion (95% confidence interval [CI]: €9.66-€9.78 billion) or €9191 (95% CI: €9134-€9252) per patient per year compared to the general population. After DAA therapy, patients with chronic HCV infection had a higher economic burden than the general population, with an additional cost of €5781 (95% CI: €5540-€6028) per patient at the fifth-year post-DAA therapy., Conclusions: A significant economic burden persists among patients with HCV infection after DAA treatment. The high proportion of patients not treated with DAA therapy supports reinforcing policies for universal access., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: The risk of mortality in people with a history of injection drug use (PHID) is high, as is the prevalence of hepatitis C virus (HCV) infection. Although direct-acting antivirals (DAA) are effective in this population in terms of sustained virological response, it is not known whether PHID benefit as much as people with no history of injection drug use from DAA-related HCV cure in terms of reduced all-cause mortality., Methods: Using Cox proportional hazards models based on the ANRS CO22 Hepather cohort data (n = 9735), we identified factors associated with all-cause mortality among HCV-infected people. We tested for interaction effects between drug injection status, HCV cure and other explanatory variables., Results: DAA-related HCV cure was associated with a 66% (adjusted hazard ratio [95% confidence interval]: 0.34 [0.29-0.39]) lower risk of all-cause mortality, irrespective of drug injection status. Detrimental effects of unhealthy alcohol use on mortality were identified in PHID only., Discussion and Conclusions: DAA-related HCV cure led to comparable benefits in terms of reduced mortality in PHID and people with no history of injection drug use. Policies and strategies to enhance DAA uptake among PHID are needed to lower mortality in this population. Clinical trial registration details: ClinicalTrials.gov: NCT01953458., (© 2023 The Authors. Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

Background and Aims: Late presentation for care of hepatitis C virus (HCV) infection - defined as having severe liver fibrosis when first consulting a specialist for HCV care - increases morbidity and mortality. Identifying the socio-behavioural correlates of late presentation is essential to improve HCV strategies to optimize HCV cascade of care. We investigated clinical and socio-behavioural correlates of late presentation for care in HCV mono-infected individuals., Methods: This study included chronic HCV mono-infected patients participating in the French national cohort ANRS CO22 HEPATHER, starting in 2012. The correlates of late presentation were estimated using a Heckman probit selection model, which takes into account the possible selection bias because of missing data in the outcome., Results: Among the 9174 study patients, 1236 had available data on liver fibrosis stage at first presentation for HCV care. Of these, 591 (47.8%) were late presenters. In a multivariable analysis adjusted for age, sex and HCV genotype, having diabetes (adjusted coefficient [95% confidence interval]: 0.55 [0.30; 0.80]), current hazardous alcohol use (0.36 [0.03; 0.69]) and current abstinence but past hazardous alcohol use (0.42 [0.19; 0.64]) (vs. current abstinence and no past hazardous use) were all independently associated with late presentation for HCV care., Conclusions: As late presentation severely affects HCV cascade of care, our findings bring important new evidence about the need to promptly identify and target people with diabetes and/or past or current hazardous alcohol use for HCV screening and treatment within the wider context of the WHO goal to eliminate HCV by 2030., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Despite universal health coverage in France, migrants face specific socioeconomic barriers that increase the likelihood of a suboptimal cascade of care for chronic hepatitis C virus (HCV) infection and impaired treatment effectiveness in this sub-population. We selected data collected from 2012 to 2018 from the ANRS CO22 HEPATHER prospective cohort study for chronic HCV participants with available data on treatment failure (defined as the presence of a detectable HCV-RNA load 12 weeks after their first DAA treatment ended). We performed multivariable Poisson regression models to test whether treatment failure rates differed significantly between HCV-infected migrants and non-migrants receiving DAA in France (cross-sectional analysis), while taking into account the former's world region of birth and other potential social vulnerability factors. Among the study population's 7,879 patients, 5,829 (74%) were non-migrants and 2,050 (26%) migrants. Median [interquartile range] age was 57 [51-65] years, 4433 (56%) were men and 369 (5%) of the entire study population had treatment failure. After multivariable adjustment, only migrants from Central Asia were at higher risk of treatment failure than non-migrants (aIRR = 2.83; 95% CI [1.72, 4.65]). Results from this large-scale study performed in France suggest a higher risk of DAA treatment failure in migrants from Central Asia than in non-migrants and confirm the overall low treatment failure rate in chronic HCV patients treated with DAA (whether migrants or not). Simplified models of care taking into account language and cultural barriers are needed to improve DAA effectiveness in migrants from Central Asia., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Obeticholic acid (OCA) and fibrates are second-line therapies for patients with primary biliary cholangitis (PBC) with an inadequate response to ursodeoxycholic acid (UDCA)., Aim: To know whether OCA and fibrates, administered together in combination with UDCA, have additive beneficial effects in patients with difficult-to-treat PBC., Methods: PBC patients treated for ≥3 months with UDCA, OCA and fibrates (bezafibrate or fenofibrate) due to failure of either second-line therapy were included in a multicentre, uncontrolled retrospective cohort study. Changes in biochemical liver tests and pruritus were analysed using a generalised linear mixed-effect model., Results: Among 58 patients included, half received OCA as second-line and fibrates as third-line therapy (Group OCA-Fibrate), while the other half had the inverse therapeutic sequence (Group Fibrate-OCA). The mean duration of triple therapy was 11 months (range 3-26). Compared to dual therapy, triple therapy was associated with a significant gain in alkaline phosphatase (ALP) reduction: 22% per first year (95% CI 12%-31%), an effect that was stronger in OCA-Fibrate than in Fibrate-OCA group. Triple therapy was associated with a 3.4 (95% CI 1.4-8.2) odds ratio (OR) of reaching normal ALP and with a significant decrease in gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin. The ORs of achieving the Paris-2 and Toronto criteria of adequate biochemical response were 6.8 (95% CI 2.8-16.7) and 9.2 (95% CI 3.4-25.1) respectively. Finally, triple therapy significantly improved pruritus in OCA-Fibrate but not in Fibrate-OCA group., Conclusions: Triple therapy with UDCA, OCA and fibrates is able to normalise biochemical liver tests and improve pruritus in patients with difficult-to-treat PBC., (© 2021 John Wiley & Sons Ltd.)

Background and Aims: Achieving sustained virological response (SVR; cure) in hepatitis C patients using a simple regimen is key to making elimination by 2030 possible. In the largest real-world analysis to date, the effectiveness of pangenotypic, panfibrotic, single-tablet, sofosbuvir/velpatasvir (SOF/VEL) once-daily for 12 weeks was assessed in 12 clinical real-world cohorts from various geographical areas, settings and treatment practices. Factors affecting risk of not achieving SVR were assessed., Methods: Adults treated with SOF/VEL 400/100 mg, without ribavirin, were included. All HCV patients reaching Week 12 or 24 post-treatment were assessed for SVR12/24. Factors associated with not achieving SVR12/24 for virological reasons were evaluated using logistic regression analysis., Results: Overall, 5552 patients were included: 13.3% treatment-experienced; 20.7% compensated cirrhotic; 30.2% genotype 1; 29.5% genotype 2; 32.9% genotype 3; 4.7% genotype 4; 3.7% HIV coinfection; 13.4% current/former intravenous drug use. Of the 5196 patients evaluated for effectiveness, 98.9% achieved SVR12/24. High SVR12/24 rates occurred in all genotypes including genotype 3 (98.3%; 1649/1677) and in those with compensated cirrhosis (97.9; 1055/1078). Only 55 patients did not achieve SVR12/24 due to a virological reason; the only factor statistically significantly associated with an increased risk of not achieving SVR12/24 was compensated cirrhosis (P = .002). Overall, 6% (332/5552) of patients did not achieve SVR12/24 for non-virological reasons (67% lost to follow-up; 26.5% early treatment discontinuation)., Conclusions: In this large cohort, representative of clinical practice, a simple 12-week regimen of SOF/VEL without ribavirin resulted in high SVR12/24 rates in diverse patient populations, even among those with compensated cirrhosis., (© 2020 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: Hepatitis B virus (HBV)/hepatitis C virus (HCV) confection has been rarely studied in nonasian series., Aim: To compare the characteristics of HBV/HCV coinfected patients to those of HBV- or HCV-monoinfected patients in the ANRS CO22 HEPATHER cohort study., Patients and Methods: Of the 20 936 included patients, 95 had HBV/HCV coinfection (hepatitis B surface antigen, anti-HCV antibody and HCV RNA positive) and were matched with 375 HBV- and 380 HCV-monoinfected patients on age, gender and time since HBV or HCV diagnosis., Results: F3-F4 fibrosis was more frequent in coinfected patients (58%) than in HBV- (32%, P < .0001), but similar in HCV-monoinfected patients (52%, P = .3142). Decompensated cirrhosis was more frequent in coinfected patients (11%) than in HBV- (2%, P = .0002) or HCV- (4%, P = .0275) monoinfected patients. Past excessive alcohol use was more frequent in coinfected patients (26%) than in HBV (12%, P = .0011), but similar in HCV monoinfected patients (32%, P = .2868). Coinfected patients had a higher proportion with arterial hypertension (42%) than HBV- (26%) or HCV-monoinfected patients (25%) (P < .003). Multivariable analysis confirmed the association between F3-F4 fibrosis and HCV infection in HBV-infected patients (OR = 3.84, 95% CI 1.99-7.43) and the association between decompensated cirrhosis and coinfection in HBV infected (OR = 5.58, 95% CI 1.42-22.0) or HCV infected patients (OR = 3.02, 95% CI 1.22-7.44)., Conclusions: HCV coinfection harmfully affects liver fibrosis in HBV patients, while decompensated cirrhosis is increased in coinfected patients compared with HBV- or HCV-monoinfected patients. HCV treatment is as safe and effective in coinfected as monoinfected patients and should be considered following the same rules as HCV monoinfected patients., (© 2017 John Wiley & Sons Ltd.)

Background & Aims: To compare the management of chronic hepatitis B (CHB) and its evolution over time in currently followed HIV-positive and HIV-negative patients., Methods: A total of 709 consecutive patients with past or present positive HBs antigenemia seen in October 2012 in 19 French participating centres were included. The data were retrospectively collected from the first visit onwards through standardized questionnaires., Results: Chronic hepatitis B was less often assessed in the 299 HIV-positive patients, who were older, more likely to be male, excessive alcohol drinkers and HBe antigen-, HCV- and HDV-positive. They were also followed up for a longer time (11.3 +/-8.8 vs. 8.6 +/-6.9 years, P < 10(-3) ) and were more frequently treated for HBV (95.3% vs. 56.8%, P < 10(-3) ). HBV was undetectable at the last visit in 80.8% of HIV-positive vs. 55.1% of HIV-negative patients (P < 10(-3) ). In multivariate analyses, undetectable HBV was significantly associated with older age, lower baseline HBV DNA, longer HBV therapy and no previous lamivudine monotherapy, but not with HIV. Cirrhosis was associated with age, male gender, Asian origin, alcoholism, HCV, HDV, but not with HIV infection. Hepatocellular carcinoma, less frequently observed in HIV-positive patients (0.7% vs. 4.7%, P = 0.002), was positively associated with age, male gender, cirrhosis and negatively associated with HIV infection (OR 0.15, 95%CI 0.03-0.67, P = 0.01)., Conclusions: Although the assessment of CHB still has to be improved in HIV-positive patients, the negative impact of HIV on the virological, histological and clinical evolution of CHB seems to be disappearing, probably because of the immunovirological impact of HAART and the more frequent and longer use of HBV therapy., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: Chronic infection with HCV remains a public health problem with approximately 150 million people infected worldwide. HCV intersects with lipid metabolism for replication and entry; and plasma concentrations of apolipoproteins have been identified as predictors for response to therapy. Herein, we conducted a screen of plasma proteins, including all apolipoproteins, to identify correlates of response to pegylated-interferon/ribavirin (PR) and HCV non-structural protein 3 (NS3) inhibitors (i.e., telaprevir/boceprevir) therapy in treatment-experienced cirrhotic patients from the ANRS CUPIC cohort., Methods: We analysed 220 baseline plasma protein concentrations in 189 patients using Luminex technology and analyzed results., Results: We identified baseline levels of apolipoprotein H (apoH) as a surrogate marker for sustained virological response (SVR). Notably, increased plasma concentration of apoH, used in combination with known clinical parameters, established a robust model with improved classification of patients as likely to achieve SVR (AUC = 0.77, Se = 66%, Sp = 72%, NRI = 39%). Moreover, we provide mechanistic information that indicates a previously unidentified role for apoH during viral entry. Using a human liver slices HCV infection model, we demonstrate that apoH limits replication., Conclusion: These data support testing of new biomarker strategies for the management of cirrhotic HCV patients and expand our understanding of how apoH may intersect with HCV infection., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Hepatitis C virus (HCV) infection increases the risk of B-cell non-Hodgkin lymphomas (B-NHL). Antiviral treatment (AT) can induce hematological responses in patients with marginal zone lymphomas (MZL). The ANRS HC-13 Lympho-C study aimed at a better understanding of the impact of AT on HCV associated B-NHL. This multicentric study enrolled 116 HCV-positive patients with B-NHL between 2006 and 2012. Cytological and histological samples were collected for centralized review. At lymphoma diagnosis, median age was 61 years and gender ratio M/F was 1. Cytohistological distribution was marginal zone lymphoma (MZL) n = 45 (39%), diffuse large B-cell lymphoma (DLBCL) n = 45 (39%), and other types n = 26 (22%). MZL patients had more frequent detection of rheumatoid factor (68% vs. 35%; P = 0.001) and more frequently mixed cryoglobulinemia (74% vs. 44%; P = 0.021) than patients with DLBCL. Among patients receiving AT, a sustained virologic response was achieved in 23 of 38 (61%) patients with MZL and in 9 of 17 (53%) with DLBCL (P = 0.42). Three-year overall survival (OS) and progression-free survival were 78% 95%CI [63-88] and 64% [48-76], respectively, without difference between cytohistological groups. Outcome analysis showed a favorable association between OS and AT in all patients (P = 0.05) and in the subgroup of MZL patients only (P = 0.04). Our data support that AT improves the outcomes of HCV-associated NHLs. The impact of new AT regimen with protease inhibitor needs to be investigated in this setting. [clinicalTrials.gov Identification number NCT01545544], (© 2014 Wiley Periodicals, Inc.)

Background: Cigarette smoking is associated with a more severe course of Crohn's disease, but individual factors determining this effect are poorly known and it is not clear whether smoking cessation is associated with an improvement in the disease activity., Aim: To assess the factors determining the harmful effect of smoking in individuals with Crohn's disease., Methods: A total of 622 consecutive patients with Crohn's disease and Crohn's disease activity index <200 were enrolled in a prospective 12-18 month cohort study. Patients were classified as current smokers, former smokers, or non-smokers. Alcohol consumption, oral contraceptive use, body mass index, and blood lipid levels were also recorded. The main outcome measure was the rate of flare-up., Results: A total of 139 current smokers (46%) developed a flare-up, vs. 79 non-smokers (30%) and 13 former smokers (23%). The relative risk of flare-up adjusted for confounding factors was 1.35 (1.03-1.76) in current smokers. This risk was increased in patients with previously inactive disease and in those who had no colonic lesions. It became significant above a threshold of 15 cigarettes per day. Former smokers behaved like non-smokers. Obesity, dyslipidaemia, and alcohol consumption had no significant effect., Conclusions: Current smoking, particularly heavy smoking, markedly increases the risk of flare-up in Crohn's disease. Former smokers have a risk similar to that of non-smokers.