definitive endoderm, hepatic progenitors, and mature hepatocytes, and to restore the missing metabolic function by transgenesis.Karyotype analysis of these cells did not show any gross genomic differences between original and reprogrammed cells.Methylome analysis showed that iPSC exhibited a methylation pattern similar to the cells they were reprogrammed from. Conclusion:We show, for the first time, the reprogramming of diseased human hepatocytes to pluripotency.Differentiation into mature hepatocytes resulted more efficient than that with fibroblast-derived iPS cells.The generation of diseased hepatocytederived human iPSC lines thus provides the basis for the study of liver disease pathogenesis, as well as safety, efficacy and clinical potential assessments of liver-derived human iPSC cells which are intrinsically more prone to hepatocyte differentiation.Thanks to this, such technology provides a potentially unlimited reservoir of cells generating genetically corrected liver cells for the treatment of human liver diseases, via auto-transplantation of genetically modified hepatocytes, avoiding LT and lifelong immunosuppression.

POSTERS3. PR plus BOC for 44 weeks (BOC/PR48).Primary endpoint was SVR 24 wks post-therapy (Roche TaqMan LLD = 9.3 IU/mL).Results: SVR was numerically higher in patients with G1a (66-73%) compared to G1b (59-64%) in the BOC arms of both studies.Similarly, the number of patients with RAVs was higher with G1a infection and the rate of detectable RAVs in all patients for whom RAV testing was performed was higher in G1a infected subjects in both studies (Table ).Conclusions: BOC/PR therapy is associated with a small but consistently higher SVR rate and lower rate of development of RAVs in patients infected with G1b compared to G1a.

Methods Randomized, open-label, prospective study comparing once-daily ATV/r with twice-daily LPV/r, both with fixeddose TDF/FTC in 883 treatment-naive patients. Treatment outcomes of HIV-RNA <50 c/mL at week 48 using confirmed virologic response (CVR) and grade 2–4 treatmentrelated AEs through week 48 are presented by pre-specified baseline HIV-RNA and CD4 cell count strata. Summary of results The proportion of responders (CVR HIV-RNA <50 c/mL, ITT) at week 48 by baseline HIV RNA strata (<100,000, 100,000–<500,000, and ≥500,000) were 83%, 76%, and 64% for ATV/r and 80%, 74%, and 61% for LPV/r (Table 1).

Methods Randomized, open-label prospective study comparing once-daily ATV/r with twice-daily LPV/r, both in combination with once-daily fixed dose combination tenofovir/ emtricitabine in antiretroviral-naive HIV-1 infected subjects. Proportion of subjects with HIV RNA <50 c/mL (confirmed virologic response/CVR), changes in CD4 cell count and lipids from baseline, and adverse events (AEs) through 48 weeks are presented among chronic HBVand/or HCV-infected (Hep+) subjects.

of results Of 1,736 subjects treated with ATV in five randomized controlled trials and one observational study, we identified 11 subjects with N88S. Of the 10 with a matched phenotype available, one subject had N88S at baseline only, and nine had N88S emerge on treatment at virologic failure: five on ATV without ritonavir (RTV), three on ATV/ RTV, and one on ATV/RTV after prior ATV without RTV. Phenotype (Monogram Biosciences) for ATV ranged from 1.26 to 27 FC (fold-change from wild-type) and was below the clinical cutoff (5.2) for ATV/RTV in 6/10 cases. Virus remained susceptible to amprenavir, darunavir, lopinavir, and tipranavir in all cases where susceptibility to the drug was included in the phenotype assay. Clinical response data on ATV were available for two subjects. The subject with N88S at baseline (ATV FC 1.38) proceeded to confirmed virologic suppression (HIV-RNA <50 c/mL) on tenofovir, emtricitabine, and ATV/RTV and remained suppressed through 96 weeks of treatment. Another subject developed N88S on the same regimen at week 16 (ATV FC 3.71) but virologically resuppressed (HIV-RNA <50 copies/mL) through 96 weeks without a change in regimen.

Until now, Belgium has been considered as a low-risk country for alveolar echinococcosis. However it was recently demonstrated by necropsy series that, in some parts of southern Belgium (Wallonia), up to 51% of the red foxes (Vulpes vulpes) may be infected by E. multilocaris. The authors, working in a university hospital in southern Belgium, described in 2002 the first autochthonous Belgian case of hepatic alveolar echinococcosis. More importantly, in 2004, they diagnosed three other patients with alveolar echinococcosis. One underwent surgical resection, but two others had bilateral pulmonary involvement at time of definite diagnosis. Palliative albendazole therapy was initiated. These patients had been diagnosed with hepatic mass from unknown origin for several months. The previous experience with the first case allowed the authors to consider and to confirm alveolar echinococcosis diagnosis, made by pathology and/or serological tests and imaging. These four patients with alveolar echinococcosis were living either in the Liege or the Luxembourg province. Considering the high prevalence of E. multilocaris infection of red foxes and the recent increase of the fox population due to rabies vaccination in southern Belgium, and also the presence of E. multilocaris infection of red foxes in northern Belgium, it is likely that not only Wallonia, but also maybe the whole Belgium, may face endemic alveolar echinococcosis in the next years.

BACKGROUND & AIMS:Entecavir is a nucleoside analogue with potent in vitro activity against lamivudine-resistant hepatitis B virus (HBV). This randomized, dose-ranging, phase 2 study compared the efficacy and safety of entecavir with lamivudine in lamivudine-refractory patients.METHODS:Hepatitis B e antigen (HBeAg)-positive and -negative patients (n = 182), viremic despite lamivudine treatment for > or =24 weeks or having documented lamivudine resistance substitutions, were switched directly to entecavir (1.0, 0.5, or 0.1 mg daily) or continued on lamivudine (100 mg daily) for up to 76 weeks.RESULTS:At week 24, significantly more patients receiving entecavir 1.0 mg (79%) or 0.5 mg (51%) had undetectable HBV DNA levels by branched chain DNA assay compared with lamivudine (13%; P < .0001). Entecavir 1.0 mg was superior to entecavir 0.5 mg for this end point (P < .01). After 48 weeks, mean reductions in HBV DNA levels were 5.06, 4.46, and 2.85 log(10) copies/mL on entecavir 1.0, 0.5, and 0.1 mg, respectively, significantly higher than 1.37 log(10) copies/mL on lamivudine. Significantly higher proportions of patients achieved normalization of alanine aminotransferase levels on entecavir 1.0, 0.5, and 0.1 mg (68%, 59%, and 47%, respectively) than on lamivudine (6%). One virologic rebound due to resistance occurred (in the 0.5-mg group).CONCLUSIONS:In HBeAg-positive and HBeAg-negative lamivudine-refractory patients, treatment with entecavir 1.0 and 0.5 mg daily was well tolerated and resulted in significant reductions in HBV DNA levels and normalization of alanine aminotransferase levels. One milligram of entecavir was more effective than 0.5 mg in this population.

ABSTRACT To evaluate the cross-resistance profile of the human immunodeficiency virus type 1 protease inhibitor (PI) atazanavir (BMS-232632), a panel of 551 clinical isolates exhibiting a wide array of PI resistance profiles and a variety of genotypic patterns were assayed for susceptibility to atazanavir and six other PIs: amprenavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir. In general, reductions in atazanavir susceptibility in vitro required several amino acid changes and were relatively modest in degree, and susceptibility was retained among isolates resistant to one or two of the currently approved PIs. There was a clear trend toward loss of susceptibility to atazanavir, as isolates exhibited increasing levels of cross-resistance to multiple PIs. Atazanavir appeared to have a distinct resistance profile relative to each of the other six PIs tested based on susceptibility comparisons against this panel of resistant isolates. Analysis of the genotypic profiles of 943 PI-susceptible and -resistant clinical isolates identified a strong correlation between the presence of amino acid changes at specific residues (10I/V/F, 20R/M/I, 24I, 33I/F/V, 36I/L/V, 46I/L, 48V, 54V/L, 63P, 71V/T/I, 73C/S/T/A, 82A/F/S/T, 84V, and 90M) and decreased susceptibility to atazanavir. While no single substitution or combination of substitutions was predictive of atazanavir resistance (change, >3.0-fold), the presence of at least five of these substitutions correlated strongly with loss of atazanavir susceptibility. Mutations associated with reduced susceptibility to each of the other six PIs were also determined.

Presenile dementia of genetic origin is often attributed to Alzheimer's disease. This disorder remains by far the commonest cause of early dementia. Pick disease and prion protein disorders are usually discussed in the differential diagnosis. We review here Nasu-Hakola syndrome (OMIM 221770), another unusual cause of presenile intellectual deterioration, in which neurological impairment occurs together with impressive destructive changes of the skeleton.