New Direct Acting Antivirals (DAA) constituted a breakthrough innovation in chronic hepatitis C (CHC) treatments. Sustain virological response rates (>90% vs 54% à 70% previously) allowed cure in shorter treatment times with a fewer adverse events (AE) compared to treatment available prior to 2014. Studies have assessed and demonstrated cost-effectiveness of new DAAs. With an estimated 72,000 patients treated in France from 2014 to 2018, this study assessed the economic impact of DAA launch. A budget impact (BI) model was constructed to estimate the BI of CHC between 2014 and 2018 and to extrapolate long-term (up to 40y) direct and indirect costs for treated CHC patients. Extrapolation was based on a Markov model that simulated the natural history of CHC. Real-world data was used for treatment patterns and patients' characteristics. Prices included published rebates, taxes. The model compared the real-world scenario (DAA) to a hypothetical scenario (no-DAA) where treatment patterns prior to 2014 were used for 2014-2018. No-DAA included lower number of treated patients and use of pegylated interferon, ribavirin, boceprevir and telaprevir only. Results compared direct costs (treatments, AEs, complications [HCC, decompensation, transplantation]) and indirect costs (loss of productivity) for both scenarios. Only 30,000 patients would have been treated without DAA between 2014 and 2018 compared to 72,000 with DAA with a respective treatment cost of 0.7 billion euros (B€) vs 2.7. Long-term extrapolation shows an estimated 1.8 vs 0.8 B€ spending in other direct costs, and 3.4 vs 1.3 in indirect costs for no-DAA compared to DAA; total cost was estimated to 6.0 vs 4.8 B€, over a billion saving for DAA. These results support that treating patients with DAAs allowed to save over a billion euros from a lifetime of 40 years and was a good investment from a collective perspective and individual benefice.

Given the high disease burden with viral hepatitis, and the advent of highly effective direct-acting antivirals against HCV infection, the WHO is now developing a global strategy to eliminate viral hepatitis by 2030.1 Increasing the uptake of HCV diagnosis and treatment will become a key intervention in achieving this goal.Although antiviral drugs should be considered for all persons with chronic HCV infection, those with significant liver fibrosis, and especially cirrhosis, should be prioritised for treatment, as they are at increased risk of hepatic complications. Current WHO guidelines for HCV recommend aspartate aminotransferase (AST)-to-platelet ratio index (APRI) or Fib-4 for the fibrosis assessment in low/middle-income countries (LMIC), because of their low cost and wide availability.2 Recently, Lemoine et al 3 developed a novel simple index called γ-glutamyl transpeptidase (GGT) to platelet …

Summary In E gypt, 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 E gypt, where circulating virus genotype 4 ( G 4), increased body mass index and co‐infection with schistosomiasis may interfere with liver fibrosis assessment. E gyptian CHC ‐infected patients with G 4 underwent a LB , an elastometry measurement ( F ibroscan © ), and serum markers ( APRI , F ib4 and F ibrotest © ). 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 F 0 F 1 vs F 2 F 3 F 4 was compared. The area under receiver operating characteristic curves was 0.70, 0.76, 0.71 and 0.75 for APRI , F ib‐4, F ibrotest© and F ibroscan©, respectively (no influence of schistosomiasis was noticed). An algorithm using the F ib4 for identifying patients with F 2 stage or more reduced by nearly 90% the number of liver biopsies. Our results demonstrated that noninvasive techniques were feasible in E gypt, for CHC G4‐infected patients. Because of its validity and its easiness to perform, we believe that F ib4 may be used to assess the F 2 threshold, which decides whether treatment should be proposed or delayed.

Although preliminary studies showed that preexposure prophylaxis (PrEP) lowers the HIV transmission in individuals with HIV, confirmative trials are ongoing and PrEP is not routinely recommended. The aim of this study was to assess whether individuals with HIV share antiretroviral (ARV) drugs for PrEP and to describe awareness and discussion on PrEP in this population. A cross-sectional survey was conducted in France in 23 representative departments of infectious diseases and internal medicine. Physicians administered an anonymous standardized questionnaire to all individuals with HIV receiving ARVs and followed between 24 and 31 October 2011. The questionnaire included items regarding PrEP (awareness; discussion with their close circle, physician or patients' association; experience), personal sociodemographic characteristics, risk behaviors and HIV status of the participants. Five hundred and ninety three participants were recruited: male 74.2% (men who have sex with men 52.4%, heterosexuals 21.6%), member of patient's association 9.8%. Half of them (50.6%) lived with a stable partner and 35.2% with an HIV-negative partner. Almost half (41.8%) were aware and 29.5% had had discussion about PrEP. In logistic regression, awareness and discussion on PrEP were more frequent: (1) among males, in patients' association members (p< 0.001 for both) and in nonheterosexuals (p=0.023 and 0.057, respectively); (2) among women, in those not living with a stable partner (p=0.035 and p=0.03, respectively) or living with an HIV-negative partner (p=0.049 and p=0.083, respectively). One percent of the participants declared having shared ARVs with someone and 8.3% reported PrEP in their close circle. Men reporting PrEP in their close circle shared ARVs more frequently than those who did not (10.3% vs. 0.2%, p < 0.001). Today, individuals with HIV do not seem to widely share personal ARVs for PrEP with seronegative people. A significant number of individuals with HIV are aware of and commonly discuss PrEP.

Background. - Hepatitis B reactivation has been observed in HIV-infected patients with isolated anti-HBc. However, the impact of isolated anti-HBc on liver fibrosis is not known in this population.Methods. - We investigated liver stiffness values (LSV) in a population of HIV-infected patients with isolated anti-HBc, and attempted to identify risk factors for high values.Results. - Fifty-one out of 69 patients (74%) had low LSV (<= 7.1 kPa). In univariate analysis, high LSV (>7.1 kPa) were associated with HCV coinfection, the duration of HIV infection, the duration of antiretroviral therapy and lipodystrophy. In age-adjusted multivariate analysis, HCV coinfection (OR 11.5; 95% CI, 3.0-62.9; P = 0.001) and lipodystrophy (OR 4.6; 95% CI, 1.1-20.7; P = 0.031) remained associated with high liver stiffness values.Conclusions. - Lipodystrophy was the only factor associated with high liver stiffness values in our population of HIV-infected patients with isolated anti-Hbc and extensive exposure to antiretroviral drugs active on HBV, apart from HCV coinfection Our study correlates to recent studies the results of which have shown that lipodystrophy, and more generally mitochondrial toxicity, was associated with advanced liver fibrosis in HIV/HCV co-infected patients. (C) 2013 Elsevier Masson SAS. All rights reserved.

706 COMPARISON OF LIVER BIOPSY, ELASTOMETRY AND SERUM MARKERS FOR LIVER FIBROSIS ASSESSMENT IN GENOTYPE 4 HCV-INFECTED PATIENTS IN EGYPT. RESULTS OF THE ANRS12184 STUDY P. Bonnard, M. El-Kassas, M. Gamal, A.B. Hassan, L. Le Fouler, A. Elsharkawy, E. Delarocque-Astagneau, M. El-Sayed, A. Abd El Hay, M. Abdel-Hamid, F. Carrat, P. Bedossa, M. Mohamed, A. Fontanet, G. Esmat, ANRS 12184 Study Group. Maladies Infectieuses et Tropicales, Hopital Tenon (AP-HP), Unite UMR-707, INSERM U707, Paris, France; Tropical Medicine Department, NHTMRI, Cairo, Egypt; Unite d’Epidemiologie des Maladies Emergentes, Institut Pasteur, Paris, France; Endemic Medicine Department, Faculty of Medicine Cairo University, Department of Microbiology, Faculty of Medicine, Minia University, NHTMRI, Cairo, Egypt; Anatomopathologie, Hopital Beaujon, Clichy, France E-mail: philippe.bonnard@tnn.aphp.fr

median total cost was $100,609 ($93,412-$112,772).Total cost was significantly lower for the 13 patients who completed responseguided therapy: $76,488 ($74,627-$90,034), p < 0.01.Total cost was greater for patients with F3-F4 fibrosis than for patients with F0-F3 fibrosis: $93,413 versus $79,390, but the difference was not significant, p = 0.15.Median total cost for the 19 patients who discontinued due to AEs was $52,158 ($27,179-$75,565), and it was $67,465 ($32,600-$75,935) for the 42 patients with on-treatment virologic failure.Conclusions: The median total cost of 48 weeks of telaprevirbased triple therapy was $100,609, including costs of preparing the patient for treatment, AE management, and post-treatment SVR testing.The median total cost per EOT was $147,321.Responseguided therapy reduced costs, while advanced fibrosis did not significantly impact them.Reductions in AEs and viral resistance are needed to optimize the clinical and economic effectiveness of HCV treatment (NIH:DA031095, DK090317; Gilead).

455 APOLIPOPROTEIN H IS STRONGLY ASSOCIATED WITH IL28B SNP GENOTYPE AND PREDICTS VIRAL CLEARANCE IN BOTH ACUTE AND CHRONIC HEPATITIS C VIRUS INFECTION M.E. Laird, A. Mohsen, R. Saleh, D. Duffy, L. Le Fouler, M. El-Daly, M. Rafik, M. Abdel-Hamid, M.K. Mohamed, P. Bonnard, V. Mallet, S. Pol, M. Albert, A. Fontanet, The ANRS HC 20 ETOC Study Group. Immunology, Institut Pasteur, Paris, France; Community Medicine Department, National Research Center, Faculty of Medicine, Ain Shams University, Cairo, Egypt; Emerging Disease Epidemiology, Institut Pasteur, Paris, France; Liver Disease Research, National Hepatology and Tropical Medicine Research Institute, Cairo, Faculty of Medicine, Minia University, Minia, Egypt; Maladies Infectieuses et Tropicales, Hopital Tenon (APHP), INSERM U 707, UPMC, Universite Paris Descartes, Institut Cochin, INSERM (IMR-S 1016), CNRS (UMR 8104), Unite d’Hepatologie, Assistance Publique, Hopitaux de Paris (APHP), Groupe Hospitalier Cochin Saint-Vincent de Paul, INSERM U 818, Conservatoire National des Arts et Metiers, Paris, France E-mail: fontanet@pasteur.fr

degree, which served as the reference; Metavir classification), and 40 were healthy volunteers. All the participants were examined using VTQ system (Siemens ACUSON S 2000 Ultrasound). The mean value of shear wave velocities (SWV) of hepatic segments s5, s6, s7, s8 were measured and compared between these groups. In addition, aspartate transaminase-to-platelet ratio index (APRI) and routine laboratory findings were included in the analysis. Results: Hepatic VTQ SWV demonstrated a significant correlation with histological stage (Spearman’s o =0.847; P < 0.001). The optimal cut-off values for predicting liver fibrosis by ARFI were 1.29m/s for F ≥2 (AUC 0.93), 1.37m/s for F ≥3 (AUC 0.97) and 1.62m/s for F4 (AUC 0.97). The optimal cut-off values for predicting liver fibrosis by APRI were 0.34m/s for F ≥2 (AUC 0.85), 0.49m/s for F ≥3 (AUC 0.87) and 0.45m/s for F4 (AUC 0.89). Conclusions: The hepatic VTQ SWV correlates well with the histological liver fibrosis stages. This novel technology enables simultaneously noninvasive assessment of liver fibrosis in patients suffering from chronic Hepatitis B with high diagnostic accuracy and convenience.

Les migrants représentent actuellement le principal groupe à risque vis-à-vis du paludisme d’importation dans les pays du Nord. La plupart sont des migrants retournant dans leur pays d’origine pour rendre visite à leur famille et amis (VFR, visiting friends and relatives). Nous avons réalisé une étude rétrospective portant sur les aspects cliniques, biologiques et thérapeutiques des accès palustres chez les migrants à l’hôpital Tenon de 2006 à 2010. Durant cette période, 239 cas de paludisme importés ont été diagnostiqués, dont 199 concernaient des migrants, 186 étaient des VFR et 13 des migrants récemment arrivés. La plupart étaient originaires d’Afrique subsaharienne et des Comores. Une chimioprophylaxie n’avait pas été suivie dans 81,2 % des cas. Pour ceux qui en avaient pris, elle était inadaptée dans 43,7 % des cas et prise irrégulièrement dans 84,4 %. Vingt-cinq accès graves à Plasmodium falciparum (13,2 %) ont été observés, deux concernaient des primo-arrivants. Un patient africain VFR est décédé. Dans notre série, deux groupes à risque étaient représentés: les sujets infectés par le VIH et les femmes enceintes. Six des premiers avaient un accès sévère et toutes les dernières présentaient une anémie. Nos résultats sont similaires à ceux observés récemment dans d’autres pays européens. L’âge moyen des VFR est en progression et leur risque de faire un accès sévère est devenu identique à celui observé chez les non-immuns. Les mesures de protection prises par cette catégorie de voyageur restent très insuffisantes.

In recent days immigrants represent the main risk group for imported malaria in northern countries. Most of them are migrants returning to their country of origin to visit friends and relatives (VFR). We retrospectively examined the main clinical, biological, and therapeutic data of all malaria cases in immigrants from 2006 to 2010 in Tenon hospital, Paris. The hospital is situated in a Paris district with an important African community. During the study period 239 imported malaria cases were observed in adults of which 199 were immigrants, 186 VFR, and 13 recently arrived. Most cases were from sub-Saharan Africa and Comoro islands. Chimioprophylaxis was not taken in 81.2% of VFR. It was inadequate in 43.7% and not taken correctly in 84.4%. Plasmodium falciparum was the most frequent species identified: 190/199 (95.5%). Severe P. falciparum malaria was observed in 25 cases (13.2%); two of them were recently arrived. One patient, African VFR, died. In this series two high-risk groups were represented: HIV-infected patients and pregnant women. Six of the HIV patients had severe malaria and all pregnant women had anemia. Our results are similar to those observed recently in other European countries. Mean age of VFR is increasing and the risk for severe P. falciparum malaria became identical to the one observed in non-immune travelers. Protection measures remain still insufficient in this population of travelers.

The HIV epidemic in France is characterized by a very low prevalence in the general population, a higher, heterogeneous and poorly documented prevalence in Sub-Saharan African immigrants, and a high prevalence in homosexual men. The aim of preventive measures in this setting is to reduce the incidence of HIV infection in the population in general and among MSM in particular, and to reduce the risk that a given individual will contract or spread the virus. Eradication of HIV from the entire population is not currently a realistic objective. Male and female condoms, post-exposure prophylaxis, and circumcision are preventive methods currently recognized and promoted worldwide. Other methods are being evaluated, such as vaginal and rectal microbicides, pre-exposure prophylaxis (PreP), and, of course, vaccination with poor results. We discuss, here, the recent results of prevention trials, especially those focusing on PreP, and those focusing on treatment as prevention (TasP) and more recently on circumcision. (C) 2012 Published by Elsevier Masson SAS.

Elastometry has demonstrated good accuracy, but little is known about its reproducibility. The aim of this study was to assess the intra- and inter-operator reproducibility of liver stiffness measurement among hepatitis C virus (HCV)-infected patients in Egypt. The study was conducted among HCV-infected patients referred for treatment evaluation in two hepatitis treatment centres of Cairo. Two operators took liver stiffness measurement two times per patient the same day. Intra- and inter-reproducibility were estimated by different methods: Bland and Altman graphics, variation coefficient, intraclass correlation coefficient and Kappa coefficient; 7.1 kPa was used as the threshold of significant (>= F2) fibrosis whenever needed. Fifty-eight patients were included in the study, and 216 measurements were taken. Failure rate was 7% and associated with overweight. For a value of 7.1 kPa, the inter-operator 95% limits of agreement were estimated at +/- 2.88 kPa. Intra-and inter-operator coefficients of variation ranged between 11% and 15%, intraclass correlation coefficients [95% confidence interval] between 0.94 [0.86-0.97] and 0.97 [0.95-0.99], and Kappa coefficients between 0.65 [0.44-0.88] and 0.92 [0.81-1.00]. The reliability of liver stiffness measurement is questionable when considering the decision to initiate antiviral therapy because of the percentage of discordance between measurements is notable, especially in the intermediate fibrosis stages.

ObjectivesAmino acid insertions in the protease gene have been reported rarely, and mainly in patients receiving protease inhibitors (PIs). The aim of the study was to assess the long-term viro-immunological follow-up of HIV-infected patients harbouring virus with protease insertions.MethodsCases of virus exhibiting protease insertions were identified in routine resistance genotyping tests. Therapeutic, immunological and virological data were retrospectively collected.ResultsEleven patients harbouring virus with a protease gene insertion were detected (prevalence 0.24%), including three PI-naive patients. The insertions were mainly located between codons 33 and 39 and associated with surrounding mutations (M36I/L and R41K). The three PI-naive patients were infected with an HIV-1 non-B subtype. Follow-up of these PI-naive patients showed that the insert-containing virus persisted for several years, was archived in HIV DNA, and displayed a reduced viral replicative capacity with no impact on resistance level. Of the eight PI-experienced patients, 63% were infected with HIV-1 subtype B; one had been antiretroviral-free for 5 years and seven were heavily PI-experienced (median duration of follow-up 24 months; range 10-62 months). The protease insertion was selected under lopinavir in four patients and under darunavir in one, in the context of major PI-resistance mutations, and following long-term exposure to PIs. The insert-containing virus persisted for a median of 32 months (range 12-62 months) and displayed no specific impact on phenotypic resistance level or viral replicative capacity.ConclusionOur data, obtained during long-term follow-up, show that insertions in the protease gene do not seem to have an impact on resistance level. This finding supports the recommendation of PI-based regimens, although further work is required to confirm it.

Background: The METAVIR score, which is the most widely used score in France, was specifically elaborated and evaluated in chronic hepatitis C and has never been validated in HIV–hepatitis virus B (HBV) co-infected patients. Aims: To validate the use of the METAVIR scoring system for activity and fibrosis on liver biopsies in co-infected HIV–HBV patients. Methods: METAVIR scoring for activity and fibrosis was first conducted on both original and virtual slides by one pathologist for comparison. Then 55 biopsies turned into virtual slides were scored by three pathologists independently. Results: The scoring comparison between virtual slides and glass slides showed an almost perfect agreement for fibrosis (weighted κ (κ w ) 0.8) and a substantial agreement for activity (κ w 0.68). The inter-observer agreement on virtual slides was moderate to almost perfect (κ w 0.52 to 0.84) for fibrosis and was dependent on the pair of pathologists considered. The best agreement was obtained in scoring advanced fibrosis and cirrhosis versus significant fibrosis versus no or mild fibrosis (κ w 0.70 to 0.84). The agreement for cirrhosis was rated moderate to substantial (κ w 0.54 to 0.79). Agreement for activity was substantial (κ w 0.66 to 0.8). Conclusions: This study validates the use of virtual slide technology to assess fibrosis and activity on liver biopsies. It also validates the use of the METAVIR score in co-infected HIV–HBV patients and illustrates the challenges in establishing the histological diagnosis of cirrhosis in the HIV–HBV context.