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Background: Drug consumption rooms (DCRs) have been developed in cities with open drug scenes, with the aim to reduce drug-related harm. In Lyon, France's second-largest city, there is no distinct drug use area, which raised doubts regarding the need for a DCR., Methods: We conducted a face-to-face survey of 264 people who use drugs (PWUDs), recruited in harm reduction or addiction treatment centers, in the streets or in squats. We assess their willingness to use a DCR, and we collected sociodemographic and medical features. Bivariable comparisons and analyses adjusted for sociodemographic parameters explored the association between willing to use a DCR and other variables, thus providing crude (ORs) and adjusted odds ratios (aORs) and 95% confidence intervals (95% CI)., Results: In total, 193 (73.1%) PWUDs accepted to participate (mean age 38.5 ± 9.3 years; 80.3% men). Among them, 64.2% declared willing to use a DCR. Being treatment-seeker (aOR 0.20, 95% CI [0.08-0.51]; p < 0.001) and not living alone (aOR 0.29; 95% CI [0.10-0.86], p = 0.025) were negatively associated with willing to use a DCR. By contrast, receiving precarity social insurance (aOR 4.12; 95% CI [1.86-9.14], p < 0.001), being seropositive for hepatitis C (aOR 3.60; 95% CI [1.20-10.84], p = 0.022), being cannabis user (aOR 2.45; 95% CI [1.01-5.99], p = 0.049), and reporting previous problems with residents (aOR 5.99; 95% CI [2.16-16.58], p < 0.001) or with the police (aOR = 4.85; 95% CI [1.43-16.39], p = 0.011) were positively associated., Conclusions: PWUDs, especially the most precarious ones, largely supported the opening of a DCR in Lyon, a city with no open drug scene., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Hepatitis C virus (HCV) is highly prevalent in people with mental disorders (PWMDs). However, in the international context of HCV elimination, no previous study has explored the features of seropositive PWMDs with vs. without a positive viral load (VL). We retrospectively retrieved all HCV serology results of patients hospitalized in 2019, 2020 and 2021 in the second-largest psychiatric hospital of France. Using the medical records of all patients found seropositive for HCV, the following data were collected: sex (male, female), age (in years), previous history of illicit drug use except cannabis (yes or no) and previous history of incarceration (yes or no). We conducted a case-control comparison of these variables between the PWMDs who had and did not have a positive VL, thus providing odds ratios and 95% confidence intervals (ORs [95% CI]). In a total of 13,276 inpatients, 2540 (19.1%) underwent at least one HCV serology; 55 of them (2.16%) were found positive. A VL count was performed for 48 of them, finding 15 (31.3%) individuals with active HCV. Compared with those with a negative VL, these 15 individuals were less likely to have previous documented illicit drug use (OR = 0.18; 95% CI [0.05-0.68]) and to have been previously incarcerated (OR = 0.23; 95% CI [0.06-0.99]); age and sex did not statistically differ. In the context of HCV elimination, PWMDs yet to be treated for HCV are more likely to be those with no identified risk factor for HCV, which supports a strategy of systematic screening for HCV among PWMDs., (© 2023 John Wiley & Sons Ltd.)

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., (© 2022. The Author(s).)

Hepatitis C is a transmissible hepatic and extra-hepatic disease caused by the hepatitis C virus (HCV). HCV develops into a chronic infection among approximately 70% of the contaminated subjects. Chronic HCV infection is estimated to affect between 0.5% and 1 % of the general population in France, which causes an important burden of disease, in particular due to the occurrence of cirrhosis and liver cancer. New antiviral drugs now allow to cure more than 95% of patients in just a few weeks of treatment with very limited safety issues. This therapeutic revolution has led the World Health Organization and many national governments to aim for an elimination of HCV, which has been defined as a 90%-reduction of the incidence rate, and a 65%-reduction in the number of HCV-related deaths on the basis of the 2015 figures. In this respect, the French Ministry of Health has recently decided to extend the ability to prescribe the new antiviral drugs to any physician. However, the elimination campaign of HCV will also need to correctly identify, screen, and treat the main target populations. If people who inject drugs (PWIDs) certainly constitute the most important population concerned by the challenge of HCV elimination, more hidden reservoirs in which HCV transmission can insidiously evolve should be identified and specifically targeted as well. Inpatient psychiatric populations might constitute one of these hidden reservoirs. International data suggest that chronic HCV infection affects approximately 5% of psychiatric inpatients in Europe. This very high prevalence estimate can in part be due to the very frequent psychiatric disorders found among the current or former PWIDs. However, a part of the seropositive patients does not report a history of drug use, and other factors could contribute to the increased risk of contamination in this population including atypical routes of transmission related to institutional promiscuity. Exploring the general profile and risk-behaviors of the psychiatric inpatients found infected by the HCV is thus warranted for future studies. Screening and treating HCV in the specific population of psychiatric patients is part of the general public health objective of eliminating HCV at a national level. Moreover, it also directly fits into the individualized psychiatric care. Many recent data suggest that HCV also has a neural tropism, in particular within glial cells, such as astrocytes or oligodendrocytes. As such, HCV foments inflammatory processes in the brain and contributes to cognitive impairments and psychiatric symptoms such as anxiety or depression. At the individual level, treating HCV infection can improve the psychiatric state and increase patients' outcomes in terms of well-being and quality of life. For all these reasons, the field of psychiatry needs local and national actions for informing and training professionals about HCV screening and treating modalities. Patient and family associations also need to be involved in this general effort of micro-elimination. A key role should be assigned to the general practitioners embedded within inpatient psychiatric units. They are the best fitted professionals to screen, treat, and empower patients, to inform and train other caregivers of the psychiatric field, and to act as a relay with hepatology teams if required. Hospital pharmacists are other important stakeholders. In a national context in which the funding of psychiatric care, including medications, is based on predefined funding envelops, innovative initiatives will have to be set up by local or national health authorities, in partnership with pharmacists, to allow for the treatment of psychiatric inpatients. In conclusion, the world of psychiatry is a possible hidden reservoir of HCV and, as such, a part of the challenge for eliminating the virus. Patients, families, and caregivers will have to be correctly sensitized and trained to play their role in the process. Specific investigations will be required to better understand why such an increased prevalence of HCV is observed in this population. Specific adaptations of the cascade of care within psychiatric settings, including access to treatment, will need to be designed, implemented, and evaluated for reaching micro-elimination of HCV in psychiatry., (Copyright © 2020 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Background: Genotype 1b is the most common HCV genotype worldwide, accounting for the largest proportion of infections in Europe, Russia, Latin America and Asia. Reducing treatment duration can improve adherence, reduce drug exposure and cost. Accordingly, we evaluated the efficacy of 8 weeks fixed-dose combination of grazoprevir-elbasvir in treatment-naïve patients, with non-severe fibrosis., Methods: HCV mono-infected and treatment naïve patients with non-severe fibrosis (Fibroscan ® <9.5 kPa and Fibrotest ®  < 0.59) were enrolled in a study which included 117 patients. Genotyping by sequencing identified five patients with non-1b genotype (two GT1a, one GT1h, one GT1e and one GT1l). Thus, we included in the final analysis 112 GT1b patients. The primary end point was the proportion of patients with HCVRNA below the lower limit of quantification 12 weeks after treatment (SVR12)., Findings: Mean age was 54 ± 13 years, 31% were men and viral load was higher than 800.000 IU/mL in 70 of 112 patients (63%). Using Fibroscan ® , 100 had F0-1 fibrosis score. FIB-4 lower than 1.45 and APRI less than 1 was found in 74/112 (66%) and 107/112 (95%) patients respectively. Relapse occurred in three patients by week 12. These three patients had a viral load higher than 6 million IU/mL and NS5A Y93H RAS (resistance-associated substitution). Then, modified intention-to-treat SVR12 for patients with genotype 1b was 109/112 (97%). By week 24; five relapses were observed and all had the Y93H RAS at relapse. SVR12 was achieved in 100% of patients with a baseline viral load below 6 million and decreased to 98% (98/100) by follow-up week 24., Interpretation: Naïve patients with genotype 1b and non-severe fibrosis can achieve an SVR12 of 97% and an SVR24 of 95%. Then, these patients can be treated with grazoprevir-elbasvir for 8 weeks., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.

Competing Interests: K. Hartig-Lavie, F. Bailly, F. Lebossé et M. Pagès-Ecochard n'ont pas fourni de déclaration de liens d'intérêts. F. Zoulim déclare avoir participé à des interventions ponctuelles pour l’entreprise Gilead, Abbvie

Background: Sexually transmitted acute hepatitis C virus (HCV) infections (AHIs) have been mainly described in human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). Cases in HIV-negative MSM are scarce. We describe the epidemic of AHI in HIV-infected and HIV-negative MSM in Lyon, France., Methods: All cases of AHI diagnosed in MSM in Lyon University Hospital from 2014 to 2017 were included. AHI incidence was determined in HIV-infected and in preexposure prophylaxis (PrEP)-using MSM. Transmission clusters were identified by construction of phylogenetic trees based on HCV NS5B (genotype 1a/4d) or NS5A (genotype 3a) Sanger sequencing., Results: From 2014 to 2017, 108 AHIs (80 first infections, 28 reinfections) were reported in 96 MSM (HIV-infected, 72; HIV-negative, 24). AHI incidence rose from 1.1/100 person-years (95 confidence interval [CI], 0.7-1.7) in 2014 to 2.4/100 person-years (95 CI, 1.1-2.6) in 2017 in HIV-infected MSM (P = .05) and from 0.3/100 person-years (95 CI, 0.06-1.0) in 2016 to 3.4/100 person-years (95 CI, 2.0-5.5) in 2017 in PrEP users (P < .001). Eleven clusters were identified. All clusters included HIV-infected MSM; 6 also included HIV-negative MSM. All clusters started with ≥1 HIV-infected MSM. Risk factor distribution varied among clusters., Conclusions: AHI incidence increased in both HIV-infected and HIV-negative MSM. Cluster analysis suggests initial transmission from HIV-infected to HIV-negative MSM through chemsex and traumatic sexual practices, leading to mixed patterns of transmission regardless of HIV status and no overlap with the general population., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Since the beginning of 2014, hepatitis C virus (HCV) recombinant forms RF2k/1b have been detected in the Rhône-Alpes French region in 10 patients originating from the Caucasus area. Circulation of this particular HCV strain is very likely to be underestimated. It is also prone to be misgenotyped when using genotyping methods based on the 5' region of the viral genome, which may lead to suboptimal treatment.

Background: We compared the efficacy of two viral hepatitis B and C (VHBC) screening strategies, relative to no intervention, among underprivileged people (UP) living in shelters in the Lyon area., Methods: Eighteen of 37 shelters were randomly sampled after stratification based on the accommodation capacity and the screening centres/shelters distance. Through randomization, the S0 strategy (no intervention), the S1 strategy [group information (GI) and referral for screening] and the S2 strategy (GI and in situ screening) were each applied in six shelters. A standardized questionnaire was offered to each participant. Follow-up of positive cases was organized via the reference centre of VHBC of Lyon., Results: The screening completion rate (SCR) among 1276 included subjects in S0, S1 and S2 was 1.5, 42.8 and 59.7%, respectively (P < 10(-6)). This rate was higher in S2 regardless of the sociodemographic variable considered. Odds ratios (OR) of screening completion (SC) was significantly higher in S1 versus S0, OR = 49.8 [95% confidence interval (CI): 26.1-102.1], in S2 versus S0, OR = 98.5 (95% CI: 51.9-200.8) and in S2 versus S1, OR = 2.0 (95% CI: 1.3-2.9). Age, country of birth and professional inactivity were independently associated with SC., Conclusions: Health authorities must ensure widespread screening of UP, which is more effective when conducted in shelters than in screening centres.

Background & Aims: To analyze the care of HCV infection in HIV-HCV coinfected patients and its progression between 2004 and 2009., Methods: Three hundred eighty HIV-HCV coinfected patients were prospectively included from November 22 to 29, 2004 (2004 survey), 416 patients from April 3 to 10, 2006 (2006 survey), and 419 patients from June 15 to 22, 2009 (2009 survey)., Results: The rate of liver biopsy decreased (14% vs. 38% vs. 56%), while the use of non-invasive liver damage tests increased (47% vs. 24% vs. ND) in the 2009, 2006, and 2004 surveys, respectively. The rate of patients that had never been treated for HCV infection progressively decreased in the 2009, 2006, and 2004 surveys (37%, 42%, and 54%). The main reasons for HCV non-treatment changed as HCV treatment was deemed less questionable and the lack of liver biopsy became a very rare reason (6%, 18%, and 34%). Among patients treated for HCV infection, the rate of sustained virological response increased (49%, 29%, and 29%). The main factors independently associated with HCV treatment were a liver fibrosis score > or =F2 (odds ratio=3.5; 95% CI 2.1-5.7), a liver biopsy activity grade > or =A2 (2.7; 1.4-5.3), a CD4 cell count > or =350 ml (2.7; 1.6-4.4), European origin (2.1; 1.3-3.4), daily alcohol consumption<30 g (2.1; 1.2-3.8), and male gender (2.0; 1.2-3.3)., Conclusion: Compared to the 2004 and 2006 surveys, the 2009 coinfected patients had liver damage assessment more frequently, more patients had received HCV treatment and more patients had achieved a sustained virological response., (Copyright 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: A screening campaign for hepatitis C virus (HCV) infection was carried out in eight health centres of Lyon from June 2003 until March 2004. The population targeted for screening was underprivileged individuals without any social insurance, protected by Couverture Mutuelle Universelle or Aide Médicale Etat (AME), to estimate the prevalence of anti-HCV antibodies in this population and to identify associated risk factors., Methods: After training in HCV infection and screening, 43 general practitioners participated in the campaign. Information about patient socio-demographics and risk factors was collected prior to proposing screening serology. Blood samples were often taken in health centres. Follow-up of positive cases was organised via the Reference Centre of HCV Infection in Lyon with possible specialised consultations in health centres., Results: The average age of the 988 individuals in the campaign was 37 years; 51% were women; 54% had a foreign nationality; 21% lived in sheltered accommodation; 19% were lodged in third-party accommodation; 9% were homeless; and 57% possessed less than euro562 (Revenu Minimum d'Insertion level). Screening was not proposed to nine patients because of medico-psychological problems. The acceptance rate for screening was 98.8% (967/979), and testing was carried out on 97.6% of these subjects (944/967). The prevalence of anti-HCV antibodies in the sample was 4.7% (44/944) (95% CI = 3.4-6.2). Nearly 80% of positive cases were unknown prior to the campaign. Multivariate logistic regression modelling identified lifetime injection drug use [odds ratios (OR) = 15.99; P < 0.0001], lifetime medical care in a foreign country (OR = 4.46; P = 0.001), and wearing tattoos (OR = 2.75; P = 0.048) as significant risk factors for carrying anti-HCV antibodies. Characteristics independently associated with HCV seropositivity were age between 40 and 49 years, AME benefits, and no social insurance., Conclusion: Wide acceptance of screening, high prevalence of anti-HCV antibodies (much higher than in the French population in general), a high proportion of positive cases unknown beforehand, and satisfactory follow-up of seropositive patients are all factors which support the need for a screening campaign targeting HCV infection in underprivileged persons living in France.

Background/aims: To determine whether addition of amantadine to pegylated interferon/ribavirin improved response rates among chronic hepatitis C patients, non-responders to interferon/ribavirin and study the dynamic of response., Methods: In a double blind, multicenter, randomized trial, 200 non-responder patients received pegylated interferon 1.5 microg/kg per week and ribavirin 800-1200 mg/day, plus either amantadine 200 mg/day or placebo for 48 weeks. Endpoints were virological responses, ALT normalization, and histological benefit overtime., Results: Twenty percent of all patients achieved a sustained virological response (SVR). This rate was 8% higher in the triple therapy group (24%) compared with the double therapy group (16%) (P = 0.22). A better virological response rate at week 24 was observed in the triple regimen group (43 vs 29%; P = 0.06), which was lost at week 48 suggesting viral escape. The biochemical response rate was also significantly higher with triple therapy at week 12 (63 vs 49%; P = 0.05) and week 24 (64 vs 49%; P = 0.03). Fibrosis stabilized or improved in 77% of all patients., Conclusions: Re-treatment of interferon/ribavirin non-responder patients should be encouraged since a substantial proportion benefits from re-treatment with pegylated interferon/ribavirin +/- amantadine. In triple therapy involving amantadine, a time wise response and an increased SVR rate in subgroups less prone to viral breakthrough suggest clues for existing controversies.

Objectives: A campaign designed to enhance screening for hepatitis C virus infection (HCV) by private practitioners was conducted in the Lyon area from April 2000 to March 2001. The target population for screening was composed of individuals with active/previous intravenous drug abuse habits or had received blood products before 1991 or who presented elevated serum transaminase levels. The objectives of the present study were to validate the campaign's organization and its impact on screening practices., Methods: The impact of the campaign was estimated from the number of prescribed and performed HCV screening and confirmation tests, the number of physicians who prescribed HCV screening tests, and the number of HCV screening tests prescribed by each physician. Indicators/practices observed during the 12-month campaign were compared with the same indicators/practices observed during the 12-month period preceding the campaign., Results: During the campaign, 15952 HCV serology tests were prescribed by 1798 of the 3052 physicians (58.9%) practising in the Lyon area. Among physicians who prescribed serology, 11.4% of the general practitioners and 10.9% of the specialists prescribed HCV serology tests for the first time during the campaign. Prescriptions for HCV serology increased significantly between the two calendar periods (+15.6%, epsilon = 17.7), similarly for general practitioners and specialists. The number of general practitioners who prescribed more than five serology tests per year increased 15.3% while the number of general practitioners who did not prescribe serology tests decreased 9.7% (P = 0.02). More HCV-positive patients were detected during the campaign (276 patients) than during the previous period (231 patients) [epsilon = 2.8]., Conclusion: When provided with pertinent information and training adapted to their medical practice, private practitioners become actively involved in screening for HCV infection.

Aim of the Study: To assess the mode of transmission and the efficacy of antiviral therapy in the outcome of treated and untreated patients with acute hepatitis C., Patients and Methods: From December 1995 to January 2001, 16 consecutive patients and their response to therapy were studied, including clinical, biochemical, virological and histological data., Results: Hepatitis C virus (HCV) exposure was IVDU (38%), needle-stick injury (19%), medical procedure (6%), piercing (6%), suspected sexual contact (19%), and unknown in 2. Among 13 patients treated for acute hepatitis C, all 12 patients who completed therapy had a biochemical and virological sustained response for more than 15 months (range: 4-36 months) after stopping therapy. Therapy was tolerated in all but one patient, who stopped after 10 weeks because of side effects. Duration of treatment, type of interferon and combination with ribavirin did not modify the response to treatment., Conclusion: These results suggest that early intervention with interferon alpha is effective in preventing the progression of acute HCV infection to chronic hepatitis in most patients regardless of duration, type of interferon, or combination with ribavirin.

Objective: A screening campaign requested by the French Health Insurance Fund was performed in the Lyon area to access the prevalence of anti-hepatitis C virus in patients from 271 general practitioners and to observe the follow-up of the patients with had positive serology. A total of 101 patients had already had hepatitis C virus antibodies and 30 patients had newly detected antibodies against hepatitis C virus. All subject received appropriate medical care. The aim of this study was to analyse medical follow-up., Methods: Follow-up was performed for one year by the patient's general practitioner or a specialist of liver disease. Clinical, biological, histological and virological data were collected and treatment was proposed when appropriate. Information was gathered anonymously by phone., Results: Follow-up was regular for 28 patients (93%). During this follow-up, ALAT levels remained within the normal limit for 13 patients (43%) and 6 of them had undetectable viral RNA by PCR. In the other patients (50%), a liver biopsy was affered to 11 patients (40%), and performed in 9 (30%). Treatment was started in 8 patients., Conclusion: The results of this study on medical follow-up are satisfying. The general practitioner plays a key role in the follow-up of patients infected by hepatitis C virus.

This study assessed the sensitivity and specificity of third-generation serological hepatitis C diagnostic tests from an analysis of the literature. The literature analysis was run using criteria from McMaster University for the assessment of diagnostic tests. The selected studies were grouped according to the type of population at high and low risk for hepatitis C virus (HCV) infection and to the type of reference test. The homogeneity of the sensitivity and the specificity was tested in each group using a Fisher's exact test. Of 132 studies, 10 were selected. When the estimates were homogeneous, summary point estimates and confidence intervals were computed; when the estimates were heterogeneous, subgroup analysis was performed. The sensitivity of third-generation enzyme-linked immunosorbent assay (ELISA3) was estimated at 98.9% (95% CI: 94-100%) in patients with chronic liver disease and at 97.2% (95% CI: 92-99%) in panels of sera. ELISA3 specificity was found at 100% in patients with chronic liver disease. The sensitivity of the third generation recombinant immunoblot assay (RIBA3) was assessed at 78.8% (95% CI: 65-89%) in haemodialysed patients. This analysis provides evidence for the good sensitivity and specificity of ELISA3 assays particularly in high risk patient groups and confirms their use for screening in these populations. Further studies are needed to assess properly RIBA3 in general population and in risk patients.

Study Objective: To estimate the prevalence of hepatitis C virus (HCV) infection among patients in general practices., Design and Participants: A screening campaign requested by the French Health Insurance Fund and involving 271 general practitioners (GPs) and 96% of the 95 medical laboratories was conducted in the Lyon area. Each GP participated for one week and offered an HCV screening to all patients aged 18-69 years during this period. Risk factors were estimated by a medical questionnaire (MQ) filled in by the physician., Main Results: From May to October 1997, 11,805 subjects were recruited into the study. Among them, 101 were known HCV positive. The MQ was filled up in 86% of the 11,704 remaining patients. Only 59% of those (6876/11,704) went to a laboratory to be tested. Fifty-one were ELISA positive of whom 30 were confirmed by RIBA or PCR. If we add 101 patients that were known HCV positive and estimate the prevalence among patients who did not go to the laboratory, this study gives a total estimated prevalence of 1.3%., Conclusions: The prevalence of HCV infection among patients of GPs is about 1.3%, very close to the estimate in the French general population. The substantial number of patients known HCV positive is probably related to the participation of GPs sensitised to HCV issues and who already have screened most of their HCV patients.

Hepatitis C is now recognized as the most common infection causing chronic liver disease in the European population. Our aim was to assess the prevalence of the antibody to hepatitis C virus (HCV), and the incidence of HCV seroconversion in the general population and the main risk groups, namely intravenous drug users, haemodialysis and transfused patients, in seven countries of the European Union, by carrying out a critical analysis of the literature. Data sources used were the Medline database and a manual search using the key words: hepatitis C, prevalence, incidence, transmission, risk factors and epidemiology. Articles published between January 1990 and March 1997 were reviewed. Articles were reviewed according to a critical analysis method regarding title, type of article, study design, period and population, tests, results and their consistency with data. The tests performed were mainly second- or third-generation serological tests. The average prevalence rate in blood donors was 1%, with a north-south gradient ranging from 0.04% to 2%. Prevalence varied from 20% to 30% in haemodialysis patients. The incidence in transfused patients was less than 1% after 1991. The prevalence in intravenous drug users was about 80%. Multicentre studies conducted in larger samples are needed to obtain more accurate and reliable results, in particular. However, the epidemiological studies available allowed us to assess the magnitude of HCV infection in Europe.

A study on the screening practices for hepatitis C was carried out among a sample of 786 general practitioners in the Lyon region. The sample comprised three groups: 272 doctors who had participated in a study of this screening, 242 doctors who had not responded to the request for participation, and 272 doctors who had refused to participate. Overall, 88.5% of the doctors surveyed had prescribed at least one HCV serology in the last 12 months, 82% had at least one HCV positive patient and of them, 59.3% had partly or completely screened these patients. The only differences between the three groups are related either to their belonging to an HIV or drug addict care network, or to a particular medical practice (study of allergies, sexology, nutrition, etc.). In fact, the first prescribe more among groups at risk and the second prescribe less and have fewer HCV positive patients.

Introduction: The combination of hepatitis C virus (HCV) infection and thyroid diseases raises several issues that are the prevalence of thyroid autoimmunity in patients with chronic hepatitis C, the prevalence of HCV infection in patients with autoimmune thyroid diseases, and the effects of interferon alpha treatment on thyroid function in chronic HCV hepatitis., Current Knowledge and Key Points: The prevalence of anti-thyroid auto-antibodies ranges from 4.6 to 15% in HCV infection, which is considered as significant by various authors. Results have to be interpreted according to the following: the type of auto-antibodies detected, the age, sex, ethnic origin of the population studied, and characteristics of the control population. Recent data are suggestive of a high prevalence of anti-thyroid auto-antibodies in females with HCV infection. An increased prevalence of HCV infection in patients with Hashimoto's thyroiditis is not confirmed. During treatment of chronic hepatitis C, interferon alpha induces thyroid dysfunctions (3 to 15% of the cases) with various clinical presentations. Hypothyroidism is more common (two out of three cases) than hyperthyroidism (one out of three cases). Hyperthyroidism followed by hypothyroidism has also been described. Clinical symptoms vary, ranging from subclinical to severe manifestations. Thyroid dysfunction may be delayed after discontinuation of the interferon treatment. Hypothyroidism is easily cured by L-thyroxine replacement therapy when necessary, and regression may be observed following discontinuation of interferon treatment. Each case of hyperthyroidism has to be precisely evaluated. Development of anti-thyroid antibodies or an increase in anti-thyroid antibodies titers is often observed during interferon alpha treatment, thus suggesting the existence of immunological mechanisms at the origin of thyroid dysfunction. Furthermore, interferon would directly act on iodine., Future Prospects and Projects: Clinical studies are still necessary to better clarify the links between HCV infection and thyroid autoimmunity, and to determine risk factors for the development of thyroid dysfunction during interferon alpha therapy. The effects of HCV and interferon alpha on thyroid autoimmunity and function have to be investigated in basic research.

French and American consensus conferences on hepatitis C confirmed the burden of that disease, especially in high risk populations. In France, the seroprevalence of HCV is about 20% among haemodialysed patients. This study aimed at describing the French screening practices in haemodialysed patients. In 1995, 1213 self-administered questionnaires were sent to nephrologists working in 715 dialysis units. The response rate was 48% (585/1213) and 485 questionnaires were analysed. In 98% of questionnaires nephrologists answered that they prescribed screening test. Routine screening with alanine amino-transferase (ALT) was reported in 98% of questionnaires, usually once a month (57%) or four times a year (23%). Routine anti-HCV serology was reported by 96%, usually once (28%) or twice (46%) a year. The two main annual strategies combining ALT and anti-HCV serology were 12 ALT and 2 serologies (21%), or 12 ALT and 1 serology (14%) per year. HCV RNA detection was reported mainly in the case of positive anti-HCV serology (70%). The study suggested heterogeneity in screening practices and revealed the need to determine the cost-effectiveness ratios of the various strategies.

Detection and quantification of hepatitis C virus (HCV) RNA levels by using the standardized qualitative Amplicor HCV and quantitative Amplicor HCV Monitor assays (Roche Molecular Systems) were evaluated in 48 patients with chronic hepatitis C treated with interferon. Results were compared with an in-house reverse transcription and polymerase chain reaction (RT-PCR) assay and the branched DNA (bDNA) assay (Quantiplex, version 1.0, Chiron Diagnostics). Concordance of the qualitative results with the Amplicor HCV and in-house RT-PCR assays occurred in 82% of the samples. All but one of the discrepant specimens were found positive by the Amplicor HCV assay and negative by the in-house RT-PCR. Among the samples with HCV RNA levels measurable with the Amplicor HCV Monitor assay, 22% had HCV RNA titers below the detection limit of the Quantiplex assay. A statistically significant correlation was found between the 2 quantitative assays, although lower titers were obtained with the Amplicor HCV Monitor assay. More important, a good correlation was observed in the evolution of viremia as measured by the 2 assays during interferon therapy. During follow-up of interferon treatments, with the Amplicor HCV Monitor assay, persisting viremia was still detected in 27% of the patients who normalised alanine aminotransferase (ALT), emphasizing the bioclinical relevance of the assay. Pre-treatment serum HCV RNA levels above 10(5) copies/ml were found more frequently in nonresponders than in responders (76% vs. 44%; P < 0.05). Given their great sensitivity and the significant correlations, the Amplicor HCV qualitative and quantitative assays appear useful for the diagnosis and management of hepatitis C infection, and especially for monitoring of therapy.

Beside the clinical manifestations usually observed during the treatment of chronic viral hepatitis with interferon, a small number of side-effects, less frequent and sometimes unexpected, have been described. These neurological, pulmonary, metabolic, cardio-vascular or psychiatric manifestations are uncommon but potentially severe. We here describe three cases of stroke that occurred during treatment with interferon in which the role played by the molecule could be questioned.

The prevalence of hepatitis C virus infection in the general population in France averages 1%. The majority of these patients are viremic with detectable HCV-RNA. Further, 75% of these individuals did not suspect they were at risk for being HCV carriers. Less than 10% of HCV carriers in France have been identified and even fewer have been treated with interferon. In addition to infection following intravenous drug use, preliminary studies suggest that most newly infected patients have become infected following surgery or endoscopy without transfusion. A large serological study of patients scheduled for surgery identified 4% HCV carriers. Other studies have determined that more than 8% of patients who received prior transfusions are now anti-HCV positive. These findings prompted the French government to initiate a screening program in France to identify patients at risk for HCV infection. This national program also involves the establishment of regional HCV reference centers to coordinate efforts among hospitals, gastroenterology/hepatology specialists, and general practitioners. The mission of the program is to promote screening and disseminate appropriate clinical practice guidelines for the management of HCV infection. The goal is to identify infected patients and initiate optimal interferon therapy as early as possible in the course of HCV infection to prevent the long-term complications secondary to infection.

Recovery of hepatitis C virus (HCV) RNA, after variable time intervals from collection, was assessed using a closed-tube system for collection, separation and transport (SST tubes). Blood from four hepatitis C-infected patients was collected in 12 SST tubes and centrifuged within 1 to 3 h of collection. Tubes were then left 0, 8, 12, 24, 48 and 72 h at room temperature and at 4 degrees C before removing serum. Hepatitis C virus RNA levels were measured by quantitative polymerase chain reaction (PCR) using the AMPLICOR HVC MONITOR assay. Hepatitis C virus RNA levels in these samples were stable for at least three days at both temperatures. Polymerase chain reaction signals never decreased by more than 0.5 log. The reproducibility of the assays showed that the quantitative PCR method can be used with the storage conditions tested here. Our data suggests that processing blood in SST tubes may be very useful in following hepatitis C virus RNA titres in infected patients, especially those receiving treatment.

Ribavirin is a nucleoside analogue with anti-viral activity against a number of DNA and RNA viruses. That molecule is administered per os and its most frequent adverse effect is haemolysis, moderate in most cases. Used alone, ribavirin normalized liver enzyme concentrations in 45% of patients while viraemia is not significantly modified. Histological improvement is observed in responder patients. The most interesting results have been obtained by associating ribavirin with interferon. In patients who have never been treated, a six-month course of ribavirin-interferon association produced a lasting and total response in 47% of patients versus 25% in patients treated with interferon alone. In relapsers, this bi-therapy produced total and prolonged response in more than 40% of cases and in 20% of non-responder patients. Lastly, that association appears promising in treating hepatitis C reinfection after liver transplantation.

Interferon alpha has confirmed its efficacy for the therapy of chronic hepatitis C. Half of the patients treated will normalize their plasma ALT at the end of a 6-month course of 3 MU thrice a week. This biochemical response is associated with a reduction of HCV RNA (viraemia) from serum and with significant improvement of liver histology. Despite those beneficial effects, 50% of treatment responders generally relapse after treatment arrest. Increasing doses to 6 MU and/or the duration of interferon therapy increases the proportion of long-term sustained responders. Combining therapy with ribavirin, a nucleoside analogue, also appears to have a similar effect.

The treatment of hepatitis C virus (HCV) infections is essentially known for chronic hepatitis C and is mainly restricted to interferon alpha. Initial trials have indicated that around 50% of the patients with chronic hepatitis C respond to alpha interferon (administered at 3 MU, thrice weekly, during 6 months) by normalizing alanine aminotransferase at the end of therapy, although 25% were found to relapse after therapy. Normalization of biochemical tests is associated with an improvement in liver histological features and with decrease or loss of HCV from serum and liver. Response to therapy is influenced by both duration and dose levels of the treatment. Following studies which showed that higher doses and longer duration were more effective than the current recommendations of 3MU thrice weekly for 6 months have recently conducted to the recent recommendation of a 12 month course of therapy using 3 MU. The outcome of therapy was also shown to be negatively influenced by longer duration of disease and presence of cirrhosis. More recently, the critical role of virological markers has been emphasized with a lower rate of response in patients infected with the genotype 1 b and a high viral load. However, these factors do not certainly predict for an individual patient the quality of the response. Therapeutical goals are: to precisely define pre-treatment scores of response able to give each individual patient the optimal treatment regimen, non responders to interferon alpha and patients with a transient benefit of therapy. Thus, development of new treatments appears critical among which those with other interferons and above all the bitherapy using ribavirin and interferon alpha which may have a marked increase in efficacy in comparison with interferon alpha used as monotherapy.

Two major hepatitis C virus genotypes, F1 and F2, corresponding to hepatitis C virus type I and type II respectively, were found in France. To investigate the correlation between infection with these genotypes (F1 and F2) and clinical features of patients, serum samples proven to be hepatitis C virus positive by polymerase chain reaction amplification on 5' non-coding region were further amplified in the NS3 region with nested polymerase chain reaction. The NS3-polymerase chain reaction products were Southern blotted and hybridized with specific probes to identify the genotype of hepatitis C virus. Of 70 samples 64 were NS3-polymerase chain reaction positive. Twenty-eight (40%) samples were hepatitis C virus type I (F1) and 34 (49%) were hepatitis C virus type II (F2), while one sample (HB) hybridized with both probes and another (HN) hybridized with neither. Some samples were sequenced, with results consistent with those of hybridization. The HB sample was related more to hepatitis C virus type II than to type I and the HN sample was divergent from both type I and type II genotypes. Clinical profiles of patients infected with hepatitis C virus type I and type II were compared. Type I infected patients were younger (p < 0.01) and more often male (p < 0.05) than those of the type II group. Nine of 28 patients in the type I infected group had a history of drug abuse, whereas none did in the type II group. Five of 22 (23%) type I infected patients and 19 of 32 (59%) type II infected patients had cirrhosis (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Initial trials indicated that around 50% of patients respond to recombinant alpha interferon by normalizing alanine aminotransferase (ALT) at the end of therapy and that half of these relapsed within 6 months following cessation of treatment. Both dose and duration of treatment are critical in the response to therapy. Higher doses and longer duration have been suggested to be more effective than the current recommendations of 3 MUI thrice weekly for 6 months based on results of these initial studies which used ALT and histological scores to evaluate the efficacy of interferon therapy. Following studies using virological markers have shown that improvements in clinical features of disease are associated with decrease or loss of hepatitis C virus (HCV) from serum and liver. The heterogeneity of the response rates between clinical centers using identical protocol emphasizes that the selection of the patients treated was as important for the outcome that the therapy regimen itself with better responses in cases without cirrhosis and with low levels of HCV RNA. Furthermore, the genotype of HCV seems to be also critical for the response rate. Virological evaluations appears therefore crucial to assess not only HCV infection but also for the indication and monitoring of therapy.

. Hepatitis C virus (HCV) infection is common in patients with Haemophilia. As in other patients, its natural history is characterized by disease progression towards cirrhosis and hepatocellular carcinoma. Many patients with hereditary bleeding disorders infected with HCV are also infected with HIV which is a factor of faster liver disease progression. In the past years, major progress has been made in the management of hepatitis C with the development of non invasive tools to assess liver fibrosis stage, i.e. fibroscan and biomarkers. With these tools, it is now possible to predict with good accuracy the liver disease stage and to take treatment decision. The landscape of antiviral therapy has evolved rapidly, especially for patients infected with HCV genotype 1. Triple therapy with interferon, ribavirin and protease inhibitors has been approved recently, the results of clinical trials showing a clear added benefit in terms of sustained virologic response in naive patients compared to interferon - ribavirin combination therapy. However, results are less promising in cirrhotic patients who failed a previous line of therapy, with a higher rate of side effects and a lower rate of virologic response in patients who qualified as null responders to IFN based therapy. Clinical trials with triple therapy are ongoing in HCV-HIV coinfected patients. Furthermore, new IFN free regimen relying on the combination of direct acting antivirals are currently being evaluated in HCV genotype 1 and non-1 infected patients. These advances provide new hope in the management of chronic hepatitis C, including patients with hereditary bleeding disorders. [ABSTRACT FROM AUTHOR]

Summary. Low pretreatment viral load has consistently been shown to be an independent predictor of sustained response (SR) in patients with chronic hepatitis C infection. We assessed the efficacy of interferon (IFN) plus ribavirin vs IFN alone in low viraemic patients (<2 millions copies/mL) who had relapsed to a previous course of IFN and the efficacy of 24 vs 48 week combination therapy in high viraemic patients. Two hundred and ninety-seven patients were randomly assigned to one of the four regimens after stratification on pretreatment viral load. All patients received IFN-α 2b (6 million units thrice weekly for 24 weeks and 3 million units thrice weekly for 24 weeks). Patients with low viraemia received either IFN-α 2b alone for 48 weeks (R1: 42 patients) or IFN-α 2b plus ribavirin (600 mg/day) for 24 weeks and IFN-α 2b alone for the next 24 weeks (R2: 48 patients). Patients with high viral load received either IFN-α 2b plus ribavirin for 24 weeks and then IFN-α 2b alone for the next 24 weeks (R3: 104 patients) or IFN-α 2b plus ribavirin for 48 weeks (R4: 103 patients). In low viraemic patients the rate of SR was 37.7% in group R1 and 59.6% in group R2 (P < 0.05). In high viraemic patients, the rate of SR was 44.7% in group R3 and 51.4% in group R4 (P: NS). Thirty-one patients discontinued treatment (10.4%) without difference regarding treatment regimen. In the regimen using ribavirin we found no difference in terms of SR between patients receiving a dose of ribavirin below 10.6 mg/kg/day (55%) or over 10.6 mg/kg/day (58%). Histological improvement occurred in 70.2% of patients regardless of the regimen. Logistic regression showed that genotype 2 and 3, Knodell score <6 and alanine aminotransferase pretreatment level >3 × upper limit of normal were significantly and independently correlated with SR. In low viraemic patients who relapsed to a previous IFN treatment, combination therapy using high-dose IFN and low-dose ribavirin is better than high-dose IFN alone. In high viraemic patients there was no benefit in increasing the duration of combination therapy from 24 to 48 weeks. In this study, it was found that low dose of ribavirin can be used safely and there is no effect of ribavirin dose on SR. [ABSTRACT FROM AUTHOR]