Elisabeth Delarocque-Astagneau

Prevalence of Hepatitis B and Hepatitis C Virus Infections in France in 2004: Social Factors Are Important Predictors After Adjusting for Known Risk Factors

To monitor the prevalence of hepatitis B and hepatitis C a cross‐sectional survey was conducted in 2004 among French metropolitan residents. A complex sampling design was used to enroll 14,416 adult participants aged 18–80 years. Data collected included demographic and social characteristics and risk factors. Sera were tested for anti‐HCV, HCV‐RNA, anti‐HBc and HBsAg. Data were analyzed with SUDAAN® software to provide weighted estimates for the French metropolitan resident population. The overall anti‐HCV prevalence was 0.84% (95% CI: 0.65–1.10). Among anti‐HCV positive individuals, 57.4% (95% CI: 43.2–70.5) knew their status. Factors associated independently with positive anti‐HCV were drug use (intravenous and nasal), blood transfusion before 1992, a history of tattoos, low socioeconomic status, being born in a country where anti‐HCV prevalence >2.5%, and age >29 years. The overall anti‐HBc prevalence was 7.3% (95%: 6.5–8.2). Independent risk factors for anti‐HBc were intravenous drug use, being a man who has sex with men, low socioeconomic status, a stay in a psychiatric facility or facility for the mentally disabled, <12 years of education, being born in a country where HBsAg prevalence >2%, age >29 and male sex. The HCV RNA and HBsAg prevalence were 0.53% (95% CI: 0.40–0.70) and 0.65% (95% CI: 0.45–0.93), respectively. Among HBsAg positive individuals, 44.8% (95% CI: 22.8–69.1) knew their status. Anti‐HCV prevalence was close to the 1990s estimates whereas HBsAg prevalence estimate was greater than expected. Screening of hepatitis B and C should be strengthened and should account for social vulnerability. J. Med. Virol. 82:546–555, 2010.

Outbreak of hepatitis C virus infection in a hemodialysis unit: potential transmission by the hemodialysis machine?

OBJECTIVE To identify the routes of transmission during an outbreak of infection with hepatitis C virus (HCV) genotype 2a/2c in a hemodialysis unit. DESIGN A matched case-control study was conducted to identify risk factors for HCV seroconversion. Direct observation and staff interviews were conducted to assess infection control practices. Molecular methods were used in a comparison of HCV infecting isolates from the case-patients and from patients infected with the 2a/2c genotype before admission to the unit. SETTING A hemodialysis unit treating an average of 90 patients. PATIENTS A case-patient was defined as a patient receiving hemodialysis with a seroconversion for HCV genotype 2a/2c between January 1994 and July 1997 who had received dialysis in the unit during the 3 months before the onset of disease. For each case-patient, 3 control-patients were randomly selected among all susceptible patients treated in the unit during the presumed contamination period of the case-patient. RESULTS HCV seroconversion was associated with the number of hemodialysis sessions undergone on a machine shared with (odds ratio [OR] per additional session, 1.3; 95% confidence interval [CI95], 0.9 to 1.8) or in the same room as (OR per additional session, 1.1; CI95, 1.0 to 1.2) a patient who was anti-HCV (genotype 2a/2c) positive. We observed several breaches in infection control procedures. Wetting of transducer protectors in the external pressure tubing sets with patient blood reflux was observed, leading to a potential contamination by blood of the pressure-sensing port of the machine, which is not accessible to routine disinfection. The molecular analysis of HCV infecting isolates identified among the case-patients revealed two groups of identical isolates similar to those of two patients infected before admission to the unit. CONCLUSIONS The results suggest patient-to-patient transmission of HCV by breaches in infection control practices and possible contamination of the machine. No additional cases have occurred since the reinforcement of infection control procedures and the use of a second transducer protector.

Risk factors for the occurrence of sporadic Salmonella enterica serotype typhimurium infections in children in France: a national case-control study.

To determine risk factors for the occurrence of sporadic Salmonella typhimurium infections among children in France, we conducted a matched case-control study. Cases were identified between 15 June and 30 September 1996. We interviewed 101 pairs of case patients and control subjects, matched for age and place of residence. The risk of illness was greater for children who ate undercooked ground beef than for those who did not (odds ratio [OR], 5.0; 95% confidence interval [CI], 1.9-13.1). Case patients were more likely than control subjects to have taken antibiotics during the month before onset of disease (OR, 2.2; 95% CI, 1.0-4.9). Case patients <5 years of age were more likely to have been in contact with a household member with diarrhea 3-10 days before onset (P=.05). Consumption of undercooked ground beef is a risk factor for the sporadic occurrence of S. typhimurium infection among children, and antibiotics may facilitate the occurrence of illness. The possibility of person-to-person transmission among young children needs to be considered.

The impact of the prevention programme of hepatitis C over more than a decade: the French experience

Summary.  To assess the impact of the French national hepatitis C prevention programme initiated in 1999, we analysed trends in hepatitis C virus (HCV) prevalence, testing and characteristics of HCV‐infected patient at first referral from 1994 to 2006. We used four data sources: Two national population‐based sero‐prevalence surveys carried out in 1994 and 2004; two surveillance networks, one based on public and private laboratories throughout France and the other on hepatology reference centres, which aim to monitor, respectively, trends of anti‐HCV screening and of epidemiological–clinical characteristics of HCV patients at first referral.Between 1994 and 2004, the anti‐HCV prevalence for adults aged 20–59 years decreased from 1.05 (95% confidence interval 0.75–1.34) to 0.71 (0.52–0.97). During the same period, those anti‐HCV positive with detectable HCV RNA decreased from 81 to 57%, whereas, the proportion of anti‐HCV positive persons aware of their status evolved from 24 to 56%. Anti‐HCV screening activity increased by 45% from 2000 to 2005, but decreased in 2006 (−10%), while HCV positivity among those tested decreased from 4.3 to 2.9%. The proportion of cirrhosis at first referral remains around 10% between 2001 and 2006, with many patients with excessive alcohol consumption (34.7% among males) or viral co‐infections (HIV seropositivity for 5.2% patients). Our analysis indicates that the national programme had a positive impact at the population level through improved prevention, screening and management. There is still a need to identify timely those at risk for earlier interventions, to assess co‐morbidities better and for a multidisciplinary approach to HCV management.

Risk factors for the occurrence of sporadic Salmonella enterica serotype enteritidis infections in children in France: a national case-control study.

To determine risk factors associated with the occurrence of sporadic cases of Salmonella enteritidis infections among children in France, we conducted a matched case-control study. Cases were identified between 1 March and 30 September 1995. One hundred and five pairs of cases and controls matched for age and place of residence were interviewed. In the 1-5 years age group, illness was associated with the consumption of raw eggs or undercooked egg-containing foods (OR 2.4, 95% CI 1.2-4.8). Storing eggs more than 2 weeks after purchase was associated with Salmonella enteritidis infection (OR 3.8, 95% CI 1.4-10.2), particularly during the summer period (OR 6.0, 95% CI 1.3-26.8). Cases were more likely to report a case of diarrhoea in the household 10-3 days before the onset of symptoms, particularly in the age group < or = 1 year (P = 0.01). This study confirms the link between eggs and the occurrence of sporadic cases of Salmonella enteritidis among children, highlights the potential role of prolonged egg storage and underlines the role of person-to-person transmission in infants.

Treatment of acute hepatitis C in human immunodeficiency virus–infected patients: The HEPAIG study

Acute hepatitis C continues to be a concern in men who have sex with men (MSM), and its optimal management has yet to be established. In this study, the clinical, biological, and therapeutic data of 53 human immunodeficiency virus (HIV)‐infected MSM included in a multicenter prospective study on acute hepatitis C in 2006‐2007 were retrospectively collected and analyzed. The mean hepatitis C virus (HCV) viral load at diagnosis was 5.8 ± 1.1 log10 IU/mL (genotype 4, n = 28; genotype 1, n = 14, genotype 3, n = 7). The cumulative rates of spontaneous HCV clearance were 11.0% and 16.5% 3 and 6 months after diagnosis, respectively. Forty patients were treated, 38 of whom received pegylated interferon and ribavirin. The mean duration of HCV therapy was 39 ± 17 weeks (24 ± 4 weeks in 14 cases). On treatment, 18/36 (50.0%; 95% confidence interval 34.3‐65.7) patients had undetectable HCV RNA at week 4 (RVR), and 32/39 (82.1%; 95 confidence interval 70.0‐94.1) achieved sustained virological response (SVR). SVR did not correlate with pretreatment parameters, including HCV genotype, but correlated with RVR (predictive positive value of 94.4%) and with effective duration of HCV therapy (64.3% for 24 ± 4 weeks versus 92.0% for longer treatment; P = 0.03). Conclusion: The low rate of spontaneous clearance and the high SVR rates argue for early HCV therapy following diagnosis of acute hepatitis C in HIV‐infected MSM. Pegylated interferon and ribavirin seem to be the best option. The duration of treatment should be modulated according to RVR, with a 24‐week course for patients presenting RVR and a 48‐week course for those who do not, irrespectively of HCV genotype. (HEPATOLOGY 2010)

A community--wide outbreak of Salmonella enterica serotype Typhimurium infection associated with eating a raw milk soft cheese in France.

In 1997, a community-wide outbreak of Salmonella enterica serotype Typhimurium (S. typhimurium) infection occurred in France. The investigation included case searching and a case-control study. A case was defined as a resident of the Jura district with fever or diarrhoea between 12 May and 8 July 1997, from whom S. typhimurium was isolated in stool or blood. One hundred and thirteen cases were identified. Thirty-three (83 %) of 40 cases but only 23 (55 %) of 42 community controls, matched for age and area of residence, reported eating Morbier cheese (Odds ratio: 6.5; 95 % Confidence Interval: 1.4-28.8). Morbier cheese samples taken from the refrigerators of two case-patients and one symptom-free neighbour cultured positive for S. typhimurium of the same phage type as the human isolates. The analysis of distribution channels incriminated one batch from a single processing plant. These findings show that an unpasteurized soft cheese is an effective vehicle of S. typhimurium transmission.

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

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

Comparison of liver biopsy and noninvasive techniques for liver fibrosis assessment in patients infected with HCV-genotype 4 in Egypt

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 F0F1 vs F2F3F4 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.

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

Although risk factors for cirrhosis in chronic hepatitis C virus (HCV) infection have been identified, the role of HCV‐genotype 3 remains controversial, and limited data are available in drug users. The aim of the study was to assess risk factors for severe liver disease (cirrhosis/hepatocellular carcinoma) in HCV‐infected drug users between 2001 and 2007 in France. Patients who reported drug use and who had been referred for HCV infection to hepatology centers from a national surveillance system were identified. The severity of liver disease was assessed clinically and histologically (Metavir score). Factors associated with severe liver disease were analyzed after estimating missing values by multiple imputation (MI). Of the 4,065 drug users naive to anti‐HCV treatment who were referred to the 26 participating centers, 8.0% had severe liver disease, 25.7% were infected with HCV‐genotype 3. Factors associated independently with an increased risk of severe liver disease were HCV‐genotype 3 (adjusted odds ratio, multiple imputation (aORMI) = 1.6, [95% confidence interval, 95% CI: 1.2–2.1]), HIV infection (aORMI = 1.8, [1.2–2.8]), male sex (aORMI = 2.0, [1.4–2.8]), age over 40 years (aORMI = 2.1, [1.6–2.9]), history of excessive alcohol consumption (aORMI = 2.8, [2.1–3.7]), and duration of infection ≥18 years (aORMI = 2.9, [2.0–4.3]). This analysis shows that HCV‐genotype 3 is associated with severe liver disease in drug users, independently of age, sex, duration of infection, alcohol consumption, and co‐infection with HIV. These results are in favor of earlier treatment for drug users infected with HCV‐ genotype 3 and confirm the need for concomitant care for excessive alcohol consumption. J. Med. Virol. 82:1647–1654, 2010. 2010 Wiley‐Liss, Inc.