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.

The 1-year Renal Biopsy Index: a scoring system to drive biopsy indication at 1-year post-kidney transplantation.

Surveillance biopsies after renal transplantation remain debatable. To drive the decision of such intervention, we propose a predictive score of abnormal histology at 1-year post-transplantation, named 1-year Renal Biopsy Index (1-RBI). We studied 466 kidney recipients from the DIVAT cohort alive with a functioning graft and a surveillance biopsy at 1-year post-transplantation. Patients displaying abnormal histology (49%) (borderline, acute rejection, interstitial fibrosis and tubular atrophy [IFTA] grade 2 or 3, glomerulonephritis) were compared to the normal or subnormal (IFTA grade 1) histology group. Obtained from a lasso penalized logistic regression, the 1-RBI was composed of recipient gender, serum creatinine at 3, 6, and 12 month post-transplantation and anticlass II immunization at transplantation (internal validation: AUC = 0.71, 95% CI [0.53-0.83]; external validation: AUC = 0.62, 95% CI [0.58-0.66]). While we could not determinate a threshold able to identify patients at high chance of normal or subnormal histology, we estimated and validated a discriminating threshold capable of identifying a subgroup of 15% of the patients with a risk of abnormal histology higher than 80%. The 1-RBI is computable online at www.divat.fr. The 1-RBI could be a useful tool to standardize 1-year biopsy proposal and may for instance help to indicate one in case of high risk of abnormal histology.

Pharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders: a systematic review with direct and network meta-analyses on nalmefene, naltrexone, acamprosate, baclofen and topiramate.

BACKGROUND AND AIMS: Pharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders (AUDs) is an emerging concept. Our objective was to explore the comparative effectiveness of drugs used in this indication. DESIGN: Systematic review with direct and network meta-analysis of double-blind randomized controlled trials (RCTs) assessing the efficacy of nalmefene, naltrexone, acamprosate, baclofen or topiramate in non-abstinent adults diagnosed with alcohol dependence or AUDs. Two independent reviewers selected published and unpublished studies on Medline, the Cochrane Library, Embase, ClinicalTrials.gov, contacted pharmaceutical companies, the European Medicines Agency and the Food and Drug Administration, and extracted data. SETTING: Thirty-two RCTs. PARTICIPANTS: A total of 6036 patients. MEASUREMENTS: The primary outcome was total alcohol consumption (TAC). Other consumption outcomes and health outcomes were considered as secondary outcomes. FINDINGS: No study provided direct comparisons between drugs. A risk of incomplete outcome data was identified in 26 studies (81%) and risk of selective outcome reporting in 17 (53%). Nalmefene [standardized mean difference (SMD) = -0.19, 95% confidence interval (CI) = -0.29, -0.10; I2  = 0%], baclofen (SMD = -1.00, 95% CI = -1.80, -0.19; one study) and topiramate (SMD = -0.77, 95% CI = -1.12, -0.42; I2  = 0%) showed superiority over placebo on TAC. No efficacy was observed for naltrexone or acamprosate. Similar results were observed for other consumption outcomes, except for baclofen (the favourable outcome on TAC was not reproduced). The number of withdrawals for safety reasons increased under nalmefene and naltrexone. No treatment demonstrated any harm reduction (no study was powered to explore health outcomes). Indirect comparisons suggested that topiramate was superior to nalmefene, naltrexone and acamprosate on consumption outcomes, but its safety profile is known to be poor. CONCLUSIONS: There is currently no high-grade evidence for pharmacological treatment to control drinking using nalmefene, naltrexone, acamprosate, baclofen or topiramate in patients with alcohol dependence or alcohol use disorder. Some treatments show low to medium efficacy in reducing drinking across a range of studies with a high risk of bias. None demonstrates any benefit on health outcomes.