Cécile Brouard

2014 French guidelines for hepatitis B and C screening: a combined targeted and mass testing strategy of chronic viruses namely HBV, HCV and HIV

Worldwide and, to a lesser extent, in France, a minority of individuals infected with hepatitis B (HBV) and C (HCV) is aware of its status. Given the current availability of highly effective anti‐HBV and anti‐HCV agents, the high rate of undiagnosed people, associated with individual and community prejudices (liver disease worsening, persistence of a hidden transmission reservoir and medicoeconomic burden of delayed care), is unacceptable.

Assessing the cost-effectiveness of hepatitis C screening strategies in France

BACKGROUND & AIMS In Europe, hepatitis C virus (HCV) screening still targets people at high risk of infection. We aim to determine the cost-effectiveness of expanded HCV screening in France. METHODS A Markov model simulated chronic hepatitis C (CHC) prevalence, incidence of events, quality-adjusted life years (QALYs), costs and incremental cost-effectiveness ratio (ICER) in the French general population, aged 18 to 80 years, undiagnosed for CHC for different strategies: S1 = current strategy targeting the at risk population; S2 = S1 and all men between 18 and 59 years; S3 = S1 and all individuals between 40 and 59 years; S4 = S1 and all individuals between 40 and 80 years; S5 = all individuals between 18 and 80 years (universal screening). Once CHC was diagnosed, treatment was initiated either to patients with fibrosis stage ≥F2 or regardless of fibrosis. Data were extracted from published literature, a national prevalence survey, and a previously published mathematical model. ICER were interpreted based on one or three times French GDP per capita (€32,800). RESULTS Universal screening led to the lowest prevalence of CHC and incidence of events, regardless of treatment initiation. When considering treatment initiation to patients with fibrosis ≥F2, targeting all people aged 40-80 was the only cost-effective strategy at both thresholds (€26,100/QALY). When we considered treatment for all, although universal screening of all individuals aged 18-80 is associated with the highest costs, it is more effective than targeting all people aged 40-80, and cost-effective at both thresholds (€31,100/QALY). CONCLUSIONS In France, universal screening is the most effective screening strategy for HCV. Universal screening is cost-effective when treatment is initiated regardless of fibrosis stage. From an individual and especially from a societal perspective of HCV eradication, this strategy should be implemented. LAY SUMMARY In the context of highly effective and well tolerated therapies for hepatitis C virus that are now recommended for all patients, a reassessment of hepatitis C screening strategies is needed. An effectiveness and cost-effectiveness study of different strategies targeting either the at-risk population, specific ages or all individuals was performed. In France, universal screening is the most effective strategy and is cost-effective when treatment is initiated regardless of fibrosis stage. From an individual and especially from a societal perspective of hepatitis C virus eradication, this strategy should be implemented.

Primary Resistance of Hepatitis B Virus to Nucleoside and Nucleotide Analogues

Nucleoside and nucleotide analogues (NUCs) targeting hepatitis B virus are capable of selecting resistant viruses upon long‐term administration as monotherapies. The prevalence of resistance‐associated substitutions (RASs) and fitness‐associated substitutions at baseline of NUC therapy and their impact on treatment responses remain unknown. A total of 232 treatment‐naïve patients chronically infected with hepatitis B virus (HBV) consecutively referred for the first time to one of French reference centres were included. The nearly full‐length HBV reverse transcriptase was sequenced by means of deep sequencing, and the sequences were analysed. RASs were detected in 25% of treatment‐naïve patients, generally representing low proportions of the viral quasispecies. All amino acid positions known to be associated with HBV resistance to currently approved NUCs or with increased fitness of resistant variants were affected, except position 80. RASs at positions involved in lamivudine, telbivudine and adefovir resistance were the most frequently detected. All patients with RASs detectable by next‐generation sequencing at baseline who were treatment‐eligible and treated with currently recommended drugs achieved a virological response. The presence of pre‐existing HBV RASs has no impact on the outcome of therapy if potent drugs with a high barrier to resistance are used.

Innovative Approach for Enhancing Testing of HIV, Hepatitis B, and Hepatitis C in the General Population: Protocol for an Acceptability and Feasibility Study (BaroTest 2016)

Background Despite substantial screening for HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) infections in France, a great number of infected persons remain undiagnosed. In this context, Santé publique France experimented with a new screening approach for HBV, HCV, and HIV infection, based on home self-sampling using dried blood spot (DBS) for blood collection. Objective The objectives of the BaroTest study were to assess the acceptability and feasibility of this approach and to update the prevalence estimates of HBV, HCV, and HIV infections in the general population. Methods Participants were enrolled using the 2016 Health Barometer, a national cross-sectional telephone survey based on a large representative sample of the general population aged 15 to 75 years (N=15,000). Upon completion of the questionnaire, any participant in the Health Barometer aged 18 to 75 years, having medical health insurance, and not under guardianship was invited to receive a self-sampling kit delivered by standard postal mail and to return the DBS card to the laboratory. The laboratory was then responsible for reporting the results to the participants. Acceptability of the protocol was based on the percentage of eligible individuals agreeing to receive the self-sampling kit, on the proportion of people returning the DBS card, and on the proportion of participants out of the total eligible population. The feasibility of the approach was based on the number of participants with adequately filled blood spots and the number of participants with blood spots for which at least one virological analysis could be performed. A complex system of reminders was implemented to increase the participation rate. Accordingly, we assumed that 35.00% (4900/14,000) of eligible persons would accept and return their DBS card. As the highest expected prevalence was for HBV infection, estimated at 0.65% in 2004, 5000 persons would make it possible to estimate this prevalence with an accuracy of approximately 0.22%. All indicators can be analyzed according to the characteristics of the participants collected in the Health Barometer questionnaire. BaroTest was approved by the French Ethics Committee (November 11, 2015) and the Commission on Information Technology and Liberties (December 24, 2015). The study has been registered by the French medical authority under number 2015-A01252-47 on November 10, 2015. Results The results on acceptability and feasibility are expected in the last quarter of 2018 and those on the prevalence estimates in the first semester of 2019. Conclusions The BaroTest results will help to inform new strategies for HIV, HBV, and HCV screening, and the Health Barometer provides a reliable updated assessment of the burden of HBV, HCV, and HIV infections in the general population in France while reducing the costs typically associated with this type of research. Registered Report Identifier RR1-10.2196/9797