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BACKGROUND: HIV-monoinfected individuals are at high risk of nonalcoholic fatty liver disease. Noninvasive tests of steatosis, nonalcoholic steatohepatitis (NASH), and fibrosis have been poorly assessed in this population. Using liver biopsy (LB) as a reference, we assessed the accuracy of noninvasive methods for their respective diagnosis: magnetic resonance imaging proton-density-fat-fraction (MRI-PDFF), FibroScan/controlled attenuation parameter (CAP), and biochemical tests. METHODS: We enrolled antiretroviral therapy-controlled participants with persistently elevated transaminases and/or metabolic syndrome, and/or lipodystrophy. All had hepatic MRI-PDFF, FibroScan/CAP, FibroTest/NashTest/SteatoTest, APRI, FIB-4, and nonalcoholic fatty liver disease-fibrosis score. A LB was indicated if suspected significant fibrosis (FibroScan ≥7.1 kPa and/or FibroTest ≥0.49). Performance was considered as good if area under a receiver operating characteristic curves (AUROCs) was >0.80. RESULTS: Among the 140 patients with suspected significant fibrosis out of the 402 eligible patients, 49 had had a LB: median age of 54 years (53-65), body mass index: 26 kg/m (24-30), steatosis in 37 (76%), NASH in 23 (47%), and fibrosis in 31 (63%) patients [F2: 7 (14%); F3: 6 (12%); and F4: 2 (4%)]. Regarding steatosis, MRI-PDFF had excellent and CAP good performances with AUROCs at 0.98 (95% confidence interval: 0.96 to 1.00) and 0.88 (0.76 to 0.99), respectively, whereas the AUROCs of SteatoTest was 0.68 (0.51 to 0.85). Regarding fibrosis (≥F2), APRI and FIB-4 had good performance with AUROCs at 0.86 (0.74 to 0.98) and 0.81 (0.67 to 0.95). By contrast, FibroScan and FibroTest had poor AUROCs [0.61 (0.43 to 0.79) and 0.61 (0.44 to 0.78)], with very low specificity. Regarding NASH, alanine aminotransferase ≥36 IU/L had good performance with AUROCs of 0.83 (0.71 to 0.94), whereas the NashTest had an AUROC of 0.60 (0.44 to 0.76). CONCLUSIONS: In HIV-monoinfected patients, MRI-PDFF and FibroScan/CAP are highly accurate for the diagnosis of steatosis. The alanine aminotransferase level and APRI should be considered for the detection of NASH and fibrosis.

Background: Dual therapy combining integrase inhibitors and NNRTIs represents a promising regimen in ageing HIV-infected individuals with long exposure to nucleoside analogues and PIs. Methods: The ANRS 163 ETRAL trial (NCT02212379) was a 96 week, multicentre, single-arm study evaluating the efficacy and safety of raltegravir (400 mg twice daily)/etravirine (200 mg twice daily) in individuals >45 years, on a PI-containing regimen who were integrase inhibitor and etravirine naive. The primary endpoint was the proportion of participants with virological success, defined by the absence of virological failure up to week 48. Main secondary outcomes included evolution of metabolic parameters, CD4/CD8 count, bone mineral density and inflammatory markers. The study was designed to show an efficacy >90%, assuming a success rate >= 95%, with a power of 80% and a 5% type-1 error. Results: One hundred and sixty-five participants (median age 52 years, duration of ART 16.9 years, viral suppression 6.9 years and CD4 count 700 cells/mm3) were enrolled. By ITT analysis, viral suppression was maintained in 99.4% of participants (95% CI = 95.6%-99.9%) at week 48 and 98.7% (95% CI = 95.0%-99.7%) at week 96. Two virological failures occurred (week 24 and week 64) without emergence of integrase inhibitor resistance. Eight participants discontinued raltegravir/etravirine for adverse events, leading to a strategy success rate of 95.1% (95% CI = 90.5%-97.5%) at week 48 and 92.7% (95% CI = 87.5%-95.8%) at week 96. Over 96 weeks, lipid fractions improved (P < 0.001), CD4/CD8 ratio increased, IFN -induced protein 10 (IP-10) decreased (-8.1%), soluble CD14 decreased (-27%, P < 0.001) bone mineral density improved and BMI increased. Conclusions: Raltegravir plus etravirine dual therapy demonstrated durable efficacy in virologically suppressed ageing patients.

Background Silent cerebral small-vessel disease (CSVD) is defined as white matter hyperintensities, silent brain infarction, or microbleeds. CSVD is responsible for future vascular events, cognitive impairment, frailty, and shorter survival. CSVD prevalence among middle-aged people living with well-controlled human immunodeficiency virus (HIV) infection (PLHIV) is unknown. Methods The French National Agency for Research on AIDS and Viral Hepatitis (ANRS) EP51 Microvascular Brain Retina and Kidney Study (MicroBREAK; NCT02082574) is a cross-sectional study with prospective enrollment of treated PLHIV, ≥50 years old with viral load controlled for ≥12 months, and frequency age- and sex-matched HIV-uninfected controls (HUCs). It was designed to estimate CSVD prevalence on 3T magnetic resonance imaging (3D fluid-attenuated inversion recovery, transversal T2-weighted gradient-echo imaging and diffusion-weighted imaging), as diagnosed by 2 blinded neuroradiologists. A logistic regression model was used to assess the impact of HIV on CSVD after adjustment for traditional risk factors. Results Between June 2013 and May 2016, 456 PLHIV and 154 HUCs were recruited. Median age was 56 and 58 years, respectively (P = .001), among whom 84.9% and 77.3%, respectively (P = .030), were men. CSVD was detected in 51.5% of PLHIV and 36.4% of HUCs with an adjusted odds ratio (aOR) of 2.3. The HIV impact differed according to age, with aOR values of 5.3, 3.7, and 1.0 for age groups 60 years, respectively (P = .022). Older age, hypertension, and lower CD4 cell count nadir were independently associated with a higher risk of CSVD among PLHIV. Conclusions HIV is an independent risk factor for CSVD. Despite sustained immunovirological control, the CSVD prevalence was twice as high among middle-aged PLHIV than HUCs. Clinical Trials Registration NCT02082574.

Background. Hepatocyte transplantation could be an alternative to whole organ transplantation to correct enzymatic disorders. To this end, it would be of major importance to use xenogeneic cells without immunosuppression. The aim of this study was to investigate the survival and metabolic activity of encapsulated xenogeneic hepatocytes in the absence of immunosuppression. For this purpose, we used Gunn rats genetically incapable of bilirubin conjugation. Methods. Xenogeneic (from guinea pigs) and allogeneic (from Lewis rats) hepatocytes (2x 10 7 ) were isolated, macroencapsulated in hydrogel hollow fibers made with an acrylonitrile-sodium methallyl-sulfonate copolymer, and transplanted into the peritoneum of Gunn rats without any immunosuppression. Plasma bilirubin levels were evaluated weekly. Bilirubin conjugates in bile and cell morphology were studied after 5 and 12 weeks, respectively. Results. In Gunn rats transplanted with xenogeneic hepatocytes, a significant decrease in the serum bilirubin level was observed between 3 and 9 weeks after transplantation when compared with controls transplanted with empty hollow fibers: it fell to 62% of the initial level at weeks 5-7 (P

Questo è un lavoro del gruppo denominato EUROMEN (European muscle envelope nucleopathies) che è parte del progetto Myo-Cluster finanziato dalla comunità Europea (QLG1-CT-1999-00870) e di cui lo IOR è il centro di coordinamento e il Dr. Luciano MERLINI dello IOR è il responsabile scientifico dell'intero progetto al quale afferiscono complessivamente 16 centri europei. Nella authorship vi sono 3 ricercatori: due dello IOR e 1 del CNR: L. Merlini,B. Talim e S. Squarzoni. Al workshop aveva partecipato anche N. M. Maraldi, che però non figura nella authorship. Il suo nome figura però nella lista dei partecipanti al workshop (pag. 187). Vengono riportati risultati originali che sono stati comunicati e discussi ad un workshop che si è tenuto in Olanda (15-16 Settembre 2000) sotto l'egida dell'European Neuromuscular Centre (ENMC). In particolare è dettagliato lo spettro clinico, molecolare e genetico dei disordini da mutazioni del gene della lamina A/C. Il quadro clinico principale è quello di una distrofia muscolare con cardiomiopatia e retrazioni muscolo- scheletriche precoci, talora scoliosi. Sono poi riportati i criteri per ottimizzare la diagnosi dal punto di vista dell'indagine cardiologia, dell'imaging dei muscolo scheletrici, e dell'esame della biopsia muscolare. Infine vengono riassunti gli aspetti di base delle membrane nucleari con l'obiettivo di identificare filoni di ricerca per una possibile individuazione della fisiopatologia di tali disordini.