Facial emotion expressivity in patients with Parkinson's and Alzheimer's disease.

Parkinson's disease (PD) and Alzheimer's disease (AD) are neurodegenerative disorders with some overlapping clinical features. Hypomimia (reduced facial expressivity) is a prominent sign of PD and it is also present in AD. However, no study has experimentally assessed hypomimia in AD and compared facial expressivity between PD and AD patients. We compared facial emotion expressivity in patients with PD, AD, and healthy controls (HCs). Twenty-four PD patients, 24 AD patients and 24 HCs were videotaped during neutral facial expressions and while posing six facial emotions (anger, surprise, disgust, fear, happiness, and sadness). Fifteen raters were asked to evaluate the videos using MDS-UPDRS-III (item 3.2) and to identify the corresponding emotion from a seven-forced-choice response format. We measured the percentage of accuracy, the reaction time (RT), and the confidence level (CL) in the perceived accuracy of the raters' responses. We found the highest MDS-UPDRS 3.2 scores in PD, and higher in AD than HCs. When evaluating the posed expression captures, raters identified a lower percentage of correct answers in the PD and AD groups than HCs. There was no difference in raters' response accuracy between the PD and AD. No difference was observed in RT and CL data between groups. Hypomimia in patients correlated positively with the global MDS-UPDRS-III and negatively with Mini Mental State Examination scores. PD and AD patients have a similar pattern of reduced facial emotion expressivity compared to controls. These findings hold potential pathophysiological and clinical implications.

Frailty is associated with the clinical expression of neuropsychological deficits in older adults.

BACKGROUND AND PURPOSE: The aim was to determine whether frailty is associated with the relationship between neuropsychological markers and global cognition in older adults. METHODS: Cross-sectional analyzes were conducted of baseline data from three large cohort studies: National Alzheimer's Coordinating Center (NACC), Rush Memory and Aging Project (MAP) and Alzheimer's Disease Neuroimaging Initiative (ADNI). Studies recruited North American participants along the spectrum of cognitive functioning (44% no cognitive impairment at baseline). A frailty index was computed in each dataset. Frailty indices, neuropsychological tests (including measures of processing speed, episodic, semantic and working memory) and Mini-Mental State Examination (MMSE) scores were the variables of interest, with age, sex, education and apolipoprotein E ε4 evaluated as confounders. RESULTS: Across all studies, 23,819 participants aged 55-104 (57% female) were included in analyzes. Frailty index scores were significantly and inversely associated with MMSE scores and significantly moderated relationships between neuropsychological test scores and MMSE scores. In participants with higher frailty index scores, lower neuropsychological test scores were more strongly associated with lower MMSE scores (standardized interaction coefficients ranged from -0.19 to -1.17 in NACC, -0.03 to -2.27 in MAP and -0.04 to -0.38 in ADNI, depending on the neuropsychological test). These associations were consistent across the different databases and were mostly independent of the composition of frailty indices (i.e., after excluding possible symptoms of dementia). CONCLUSIONS: Amongst older Americans, frailty is associated with the cognitive expression of neuropsychological deficits. Implementation of frailty assessment in routine neurological and neuropsychological practice should be considered to optimize care outcomes for older adults.

Relationship between default mode network and resting-state electroencephalographic alpha rhythms in cognitively unimpaired seniors and patients with dementia due to Alzheimer's disease.

Here we tested the hypothesis of a relationship between the cortical default mode network (DMN) structural integrity and the resting-state electroencephalographic (rsEEG) rhythms in patients with Alzheimer's disease with dementia (ADD). Clinical and instrumental datasets in 45 ADD patients and 40 normal elderly (Nold) persons originated from the PDWAVES Consortium (www.pdwaves.eu). Individual rsEEG delta, theta, alpha, and fixed beta and gamma bands were considered. Freeware platforms served to derive (1) the (gray matter) volume of the DMN, dorsal attention (DAN), and sensorimotor (SMN) cortical networks and (2) the rsEEG cortical eLORETA source activities. We found a significant positive association between the DMN gray matter volume, the rsEEG alpha source activity estimated in the posterior DMN nodes (parietal and posterior cingulate cortex), and the global cognitive status in the Nold and ADD participants. Compared with the Nold, the ADD group showed lower DMN gray matter, lower rsEEG alpha source activity in those nodes, and lower global cognitive status. This effect was not observed in the DAN and SMN. These results suggest that the DMN structural integrity and the rsEEG alpha source activities in the DMN posterior hubs may be related and predict the global cognitive status in ADD and Nold persons.

Normative data beyond the total scores: a process score analysis of the Rey's 15 word test in healthy aging and Alzheimer's Disease.

BACKGROUND: The Rey's 15 words test is currently the most frequently used task in Italy to detect memory deficits in AD. The current standardised version is however quite outdated and lacks some cognitive indexes which may highlight problems in recall or encoding processes. The aim of the study was to update the normative data of the test and to consider some variables which were not accounted for in the original study, that is, recognition, learning rate and forgetfulness. We also adopted the process scores approach to ascertain the effects of serial position (primacy and recency). METHODS: Three hundred ninety-six healthy participants were recruited. To detect any variables useful for intercepting the early stages of dementia, a group of 208 patients in the very early stage of AD was also recruited. Linear models were used to calculate the corrections scores for age, education, and gender, and ROCs were used to calculate cut-offs based on the maximum sum of sensitivity and specificity and the positive and negative predictive values. RESULTS: All main indexes showed excellent Area Under the Curve (0.90-1), strong sensitivity and PPVs for distinguishing between the HCs and AD participants. However, the Intrusions index performed poorly in all parameters. CONCLUSION: The study provides updated, normative data which may be reliably used as a cognitive marker to detect early AD. The strength of the study is the large sample size and the number of indexes which make it possible to explore the utility of memory test process scores.

Smelling TNT: Trends of the Terminal Nerve.

There is very little knowledge regarding the terminal nerve, from its implications in the involvement and pathogenesis of certain conditions, to its embryological origin. With this review, we try to summarize the most important evidence on the terminal nerve, aiming to clarify its anatomy and the various functions attributed to it, to better interpret its potential involvement in pathological processes. Recent studies have also suggested its potential role in the control of human reproductive functions and behaviors. It has been hypothesized that it plays a role in the unconscious perception of specific odors that influence autonomic and reproductive hormonal systems through the hypothalamic-pituitary-gonadal axis. We used the PubMed database and found different articles which were then selected independently by three authors. We found 166 articles, of which, after careful selection, only 21 were analyzed. The terminal nerve was always thought to be unimportant in our body. It was well studied in different types of animals, but few studies have been completed in humans. For this reason, its function remains unknown. Studies suggest a possible implication in olfaction due to the anatomical proximity with the olfactive nerve. Others suggest a more important role in reproduction and sexual behaviors. New emerging information suggests a possible role in Kallmann syndrome and COVID-19.

Multimorbidity patterns and 18-year transitions from normal cognition to dementia and death: A population-based study.

BACKGROUND: Several chronic diseases accelerate cognitive decline; however, it is still unknown how different patterns of multimorbidity influence individuals' trajectories across the cognitive continuum. OBJECTIVES: We aimed to investigate the impact of multimorbidity and of specific multimorbidity patterns on the transitions across cognitive stages (normal cognition, cognitive impairment, no dementia [CIND], dementia) and death. METHODS: We included 3122 dementia-free individuals from the Swedish National study on Aging and Care in Kungsholmen. Using fuzzy c-means cluster analysis, multimorbid participants were classified into mutually exclusive groups characterized by commonly coexisting chronic diseases. Participants were followed up to 18 years to detect incident CIND, dementia, or death. Transition hazard ratios (HRs), life expectancies, and time spent in different cognitive stages were estimated using multistate Markov models. RESULTS: At baseline, five multimorbidity patterns were identified: neuropsychiatric, cardiovascular, sensory impairment/cancer, respiratory/metabolic/musculoskeletal, and unspecific. Compared to the unspecific pattern, the neuropsychiatric and sensory impairment/cancer ones showed reduced hazards of reverting from CIND to normal cognition (HR 0.53, 95% CI 0.33-0.85 and HR 0.60, 95% CI 0.39-0.91). Participants in the cardiovascular pattern exhibited an increased hazard of progression from CIND to dementia (HR 1.70, 95% CI 1.15-2.52) and for all transitions to death. Subjects with the neuropsychiatric and cardiovascular patterns showed reduced life expectancy at age 75, with an anticipation of CIND (up to 1.6 and 2.2 years, respectively) and dementia onset (up to 1.8 and 3.3 years, respectively). CONCLUSIONS: Multimorbidity patterns differentially steer individual trajectories across the cognitive continuum of older adults and may be used as a risk stratification tool.

Cidofovir for treating complicated monkeypox in a man with acquired immune deficiency syndrome.

In July 23, the World Health Organization (WHO) declared monkeypox (MPX) a global health emergency of international concern given its rapid spread. So far, most current MPX outbreaks have involved young men who have sex with men (MSM), although with overall mild, self-limiting clinical manifestations. We aim to describe the case of an HIV positive young MSM whose status of immune compromission probably contributed to a more severe clinical course of MPX disease, thus requiring hospitalization and antiviral treatment. He was effectively treated with Cidofovir that may be considered as a valuable component of a multi-faceted management of severe MPX.

An updated overview of recent and ongoing deep brain stimulation (DBS) trials in patients with dementia: a systematic review.

BACKGROUND: Dementia affects more than 55 million people worldwide. Several technologies have been developed to slow cognitive decline: deep brain stimulation (DBS) of network targets in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) have been recently investigated. OBJECTIVE: This study aimed to review the characteristics of the populations, protocols, and outcomes of patients with dementia enrolled in clinical trials investigating the feasibility and efficacy of DBS. MATERIALS AND METHODS: A systematic search of all registered RCTs was performed on Clinicaltrials.gov and EudraCT, while a systematic literature review was conducted on PubMed, Scopus, Cochrane, and APA PsycInfo to identify published trials. RESULTS: The literature search yielded 2122 records, and the clinical trial search 15 records. Overall, 17 studies were included. Two of 17 studies were open-label studies reporting no NCT/EUCT code and were analysed separately. Of 12 studies investigating the role of DBS in AD, we included 5 published RCTs, 2 unregistered open-label (OL) studies, 3 recruiting studies, and 2 unpublished trials with no evidence of completion. The overall risk of bias was assessed as moderate-high. Our review showed significant heterogeneity in the recruited populations regarding age, disease severity, informed consent availability, inclusion, and exclusion criteria. Notably, the standard mean of overall severe adverse events was moderately high (SAEs: 9.10 ± 7.10%). CONCLUSION: The population investigated is small and heterogeneous, published results from clinical trials are under-represented, severe adverse events not negligible, and cognitive outcomes uncertain. Overall, the validity of these studies requires confirmation based on forthcoming higher-quality clinical trials.

An ontology-based approach for modelling and querying Alzheimer's disease data.

BACKGROUND: The recent advances in biotechnology and computer science have led to an ever-increasing availability of public biomedical data distributed in large databases worldwide. However, these data collections are far from being "standardized" so to be harmonized or even integrated, making it impossible to fully exploit the latest machine learning technologies for the analysis of data themselves. Hence, facing this huge flow of biomedical data is a challenging task for researchers and clinicians due to their complexity and high heterogeneity. This is the case of neurodegenerative diseases and the Alzheimer's Disease (AD) in whose context specialized data collections such as the one by the Alzheimer's Disease Neuroimaging Initiative (ADNI) are maintained. METHODS: Ontologies are controlled vocabularies that allow the semantics of data and their relationships in a given domain to be represented. They are often exploited to aid knowledge and data management in healthcare research. Computational Ontologies are the result of the combination of data management systems and traditional ontologies. Our approach is i) to define a computational ontology representing a logic-based formal conceptual model of the ADNI data collection and ii) to provide a means for populating the ontology with the actual data in the Alzheimer Disease Neuroimaging Initiative (ADNI). These two components make it possible to semantically query the ADNI database in order to support data extraction in a more intuitive manner. RESULTS: We developed: i) a detailed computational ontology for clinical multimodal datasets from the ADNI repository in order to simplify the access to these data; ii) a means for populating this ontology with the actual ADNI data. Such computational ontology immediately makes it possible to facilitate complex queries to the ADNI files, obtaining new diagnostic knowledge about Alzheimer's disease. CONCLUSIONS: The proposed ontology will improve the access to the ADNI dataset, allowing queries to extract multivariate datasets to perform multidimensional and longitudinal statistical analyses. Moreover, the proposed ontology can be a candidate for supporting the design and implementation of new information systems for the collection and management of AD data and metadata, and for being a reference point for harmonizing or integrating data residing in different sources.

Mononuclear or Coordination Polymer Complexes? Both Are Possible for 3,6,9-Trioxaundecanedioic Acid.

Investigating the driving forces leading to the formation of a specific supramolecular architecture among a wide spectrum of all the possibly obtainable structures is not an easy task. The contemporary literature provides several models for correctly predicting the thermodynamically accessible structures that can originate from a library of building blocks. Definitions are rigid by their very nature, so their application may sometimes require a shift in perspective. In the study presented herein, we describe the crystal structures of three metallo-supramolecular architectures assembled from deprotonated derivatives of 3,6,9-trioxaundecanedioic acid and Mn(II), Co(II) and Zn(II). In the Mn(II) case, the complexation resulted in a complex of a discrete/heptacoordinated nature, whereas the other two structures appeared as helical polymers. To explain such an anomaly, in this work, we describe how the interplay between the flexibility of the ligand spacer and the number of coordinating atoms involved determines the divergent or convergent organisation of the final coordination architecture.

What we know and still ignore on COVID-19 immune pathogenesis and a proposal based on the experience of allergic disorders.

The coronavirus disease 2019 (COVID-19) pandemic started in March 2020 and caused over 5 million confirmed deaths worldwide as far August 2021. We have been recently overwhelmed by a wide literature on how the immune system recognizes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and contributes to COVID-19 pathogenesis. Although originally considered a respiratory viral disease, COVID-19 is now recognized as a far more complex, multi-organ-, immuno-mediated-, and mostly heterogeneous disorder. Though efficient innate and adaptive immunity may control infection, when the patient fails to mount an adequate immune response at the start, or in advanced disease, a high innate-induced inflammation can lead to different clinical outcomes through heterogeneous compensatory mechanisms. The variability of viral load and persistence, the genetic alterations of virus-driven receptors/signaling pathways and the plasticity of innate and adaptive responses may all account for the extreme heterogeneity of pathogenesis and clinical patterns. As recently applied to some inflammatory disorders as asthma, rhinosinusitis with polyposis, and atopic dermatitis, herein we suggest defining different endo-types and the related phenotypes along COVID-19. Patients should be stratified for evolving symptoms and tightly monitored for surrogate biomarkers of innate and adaptive immunity. This would allow to preventively identify each endo-type (and its related phenotype) and to treat patients precisely with agents targeting pathogenic mechanisms.

A pathogenic integrated view explaining the different endotypes of asthma and allergic disorders.

The inflammation of allergic diseases is characterized by a complex interaction between type 2 and type 3 immune responses, explaining clinical symptoms and histopathological patterns. Airborne stimuli activate the mucosal epithelium to release a number of molecules impacting the activity of resident immune and environmental cells. Signals from the mucosal barrier, regulatory cells, and the inflamed tissue are crucial conditions able to modify innate and adaptive effector cells providing the selective homing of eosinophils or neutrophils. The high plasticity of resident T- and innate lymphoid cells responding to external signals is the prerequisite to explain the multiplicity of endotypes of allergic diseases. This notion paved the way for the huge use of specific biologic drugs interfering with pathogenic mechanisms of inflammation. Based on the response of the epithelial barrier, the activity of resident regulatory cells, and functions of structural non-lymphoid environmental cells, this review proposes some immunopathogenic scenarios characterizing the principal endotypes which can be associated with a precise phenotype of asthma. Recent literature indicates that similar concepts can also be applied to the inflammation of other non-respiratory allergic disorders. The next challenges will consist in defining specific biomarker(s) of each endotype allowing for a quick diagnosis and the most effective personalized therapy.

Which DFT factors influence the accuracy of 1H, 13C and 195Pt NMR chemical shift predictions in organopolymetallic square-planar complexes? New scaling parameters for homo- and hetero-multimetallic compounds and their direct applications.

Because of their chemical heterogeneity, stereochemical complexity and the presence of heavy atoms involving orbitals with high quantum number L, organopolymetallic complexes require considerable focus during their NMR spectral interpretation. Until now, computational NMR studies have mainly focused on mono-nuclear species; at the same time, recent literature displays that new synthetic procedures are being developed to efficiently insert two or more metals into organic scaffolds, and hence an ad hoc theoretical NMR protocol is urgently required. This study, exploiting a solid calibration set, provides a comprehensive overview of the 1H, 13C and 195Pt NMR prediction trends when DFT parameters are scanned. The best performing levels for 1H (GIAO/TPSSTPSS/x2c-TZVPPallS/SUPERFINE/SMD), 13C (GIAO/CAM-B3LYP/Jorge-TZP/SUPERFINE/CPMC) and 195Pt (GIAO/TPSSTPSS/LANL2DZ/SUPERFINE/SMD) were employed as guidance for important NMR elucidations including both regio- and stereo-chemical features. Finally, the presented fitted scaling factors were proved to have a considerable transferibility between different solvents without re-parameterization.

A Plasma Circular RNA Profile Differentiates Subjects with Alzheimer's Disease and Mild Cognitive Impairment from Healthy Controls.

The most frequently used biomarkers to support the diagnosis of Alzheimer's Disease (AD) are Aß42, total-Tau, and phospho-tau protein levels in CSF. Moreover, magnetic resonance imaging is used to assess hippocampal atrophy, 18F-FDG PET to identify abnormal brain metabolism, and PET imaging for amyloid deposition. These tests are rather complex and invasive and not easily applicable to clinical practice. Circulating non-coding RNAs, which are inherently stable and easy to manage, have been reported as promising biomarkers for central nervous system conditions. Recently, circular RNAs (circRNAs) as a novel class of ncRNAs have gained attention. We carried out a pilot study on five participants with AD and five healthy controls (HC) investigating circRNAs by Arraystar Human Circular RNA Microarray V2.0. Among them, 26 circRNAs were differentially expressed (FC ≥ 1.5, p < 0.05) in participants with AD compared to HC. From a top 10 of differentially expressed circRNAs, a validation study was carried out on four up-regulated (hsa_circRNA_050263, hsa_circRNA_403959, hsa_circRNA_003022, hsa_circRNA_100837) and two down-regulated (hsa_circRNA_102049, hsa_circRNA_102619) circRNAs in a larger population. Moreover, five subjects with mild cognitive impairment (MCI) were investigated. The analysis confirmed the upregulation of hsa_circRNA_050263, hsa_circRNA_403959, and hsa_circRNA_003022 both in subjects with AD and in MCI compared to HCs. We also investigated all microRNAs potentially interacting with the studied circRNAs. The GO enrichment analysis shows they are involved in the development of the nervous system, and in the cellular response to nerve growth factor stimuli, protein phosphorylation, apoptotic processes, and inflammation pathways, all of which are processes related to the pathology of AD.

Operationalization of a frailty index in patients with multiple sclerosis: A cross-sectional investigation.

BACKGROUND: Frailty is an age-related status of increased vulnerability to stressors caused by the accumulation of multiple health deficits. This construct may allow to capture the clinical complexity of patients with multiple sclerosis (MS). OBJECTIVE: To investigate the relationship between frailty and the clinical manifestations of MS. METHODS: Patients with MS were consecutively enrolled at five tertiary dedicated services. Disability and fatigue were assessed. The phenotypes of MS were also identified. Frailty was measured using a frailty index (FI), computed by cumulatively considering 42 age-related multidimensional health deficits. RESULTS: Overall, 745 MS patients (mean age = 48.2 years, standard deviation = 11.7 years; women 68%) were considered. The median FI value was 0.12 (interquartile range = 0.05-0.19) and the 99th percentile was 0.40. FI scores were associated with MS disease duration, disability, fatigue, as well as with the number of previous disease-modifying treatments and current symptomatic therapies. A logistic regression analysis model showed that FI score was independently associated with the secondary progressive phenotype. CONCLUSION: Frailty is significantly associated with major characteristics of MS. The findings of the present cross-sectional investigation should be explored in future longitudinal studies.

Do Secondary Electrostatic Interactions Influence Multiple Dihydrogen Bonds? AA-DD Array on an Amine-Borane Aza-Coronand: Theoretical Studies and Synthesis.

Hydrogen bond plays a key role in a wide range of inorganic, organic, as well as biological systems. The understanding on how the chemical environment can affect this kind of interaction is crucial to predict its binding strength and consequently the robustness and the dynamic properties of many supramolecular systems. In this paper a new donor-acceptor complex was synthesized and characterized by SCXRD, showing for the first time in an organic system an AA-DD pattern of a particular hydrogen interaction, called dihydrogen bond. Over 250 functionals were computationally evaluated to select the best method to reproduce the binding interaction geometry of this new pattern. Moreover, a new vector force model was used to split the contribution of primary and secondary electrostatic interactions (SEIs), in order to evaluate how the latter one can modify the binding strength of this unusual hydrogen-hydrogen interaction.

A Time-Based Electronic Front-End for a Capacitive Particle Matter Detector.

This paper introduces the electronic interface for a capacitive airborne particle matter detector. The proposed circuit relies on two matched ring oscillators and a mixer to detect the frequency difference induced by the deposition of a particle onto an interdigitated capacitor, which constitutes the load of one of the oscillators. The output of the mixer is digitized through a simple counter. In order to compensate the oscillation frequency offset of the two ring oscillators due to process and mismatch variations, a capacitive trimming circuit has been implemented. The sensor is connected to host through an I2C interface for communication and configuration. The sensor has been implemented using a standard 130-nm CMOS technology by STMicroelectronics and occupies 0.12-mm2 die area. Experimental measurements using talcum powder show a sensitivity of 60 kHz/fF and a 3σ resolution equal to 165 aF.

Intermolecular Forces Driving Hexamethylenetetramine Co-Crystal Formation, a DFT and XRD Analysis.

Interest in co-crystals formation has been constantly growing since their discovery, almost a century ago. Such success is due to the ability to tune the physical-chemical properties of the components in solid state by avoiding a change in their molecular structure. The properties influenced by the co-crystals formation range from an improvement of mechanical features and chemical stability to different solubility. In the scientific research area, the pharmacological field is undoubtedly one of those in which an expansion of the co-crystal knowledge can offer wide benefits. In this work, we described the crystalline structure of hexamethylenetetramine co-crystallized with the isophthalic acid, and we compared it with another co-crystal, showing the same components but different stoichiometry. To give a wider overview on the nature of the interactions behind the observed crystal packing and to rationalize the reasons of its formation, a computational analysis on such structures was carried out.

Counting deficits or diseases? The agreement between frailty and multimorbidity in subjects with cognitive disturbances.

In the present study, we explored the relationship between multimorbidity and frailty in a population of older individuals with cognitive disturbances attending a memory clinic. All subjects consecutively attending the Memory Clinic of the Department of Human Neuroscience, "Sapienza" University of Rome, between January 2017 and April 2018 for a first neurological evaluation were considered for the present analysis. Multimorbidity was defined as the simultaneous presence of two or more diseases in the same individual. A Frailty Index was computed by considering 44 age-related, multidimensional health deficits. Overall, 185 subjects were recruited in the study. A condition of multimorbidity was detected in 87.6% of the sample, whereas only the 44.6% of the study population was considered as frail. A poor agreement was observed between multimorbidity and frailty. The present findings confirm that counting diseases or health deficits may provide discordant information concerning the risk profile of older subjects.

Influence of HLA-B18 on liver fibrosis progression in a cohort of HIV/HCV coinfected individuals.

Liver fibrosis is accelerated in human immunodeficiency virus/hepatitis C virus (HIV/HCV) coinfected compared with HCV monoinfected patients, due to multiple cofactors. Recently, HLA-B18 haplotype has been associated with short-term liver disease progression in this population. Our aim was to assess the influence of HLA-B18 on the fibrosis process in HIV/HCV coinfected individuals, untreated for HCV, during a long-term follow-up. All consecutive HIV/HCV co-infectedcoinfected patients followed in our center, with positive HCV-RNA and available human leukocyte antigen (HLA) haplotypes (determined by sequence-specific oligonucleotide primed polymerase chain reaction and simple sequence repeats polymerase chain reaction using Luminex Technology) were included. Liver fibrosis progression was assessed by means of fibrosis-4 index for liver fibrosis (FIB-4) and AST to platelet ratio index. The association between FIB-4 score over time and laboratory and clinical parameters, including HLA, was evaluated by univariate and multivariate multilevel generalized linear models. A total of 29 out of 148 screened patients were excluded because of spontaneous HCV clearance (27% were HLA-B18+). Among the remaining 119 individuals (82% males; median age at first visit = 30 years [interquartile range, IQR, 26-35]; median follow-up = 21.5 years [IQR, 15-25]), 26% were HLA-B18+. No baseline differences were evidenced between HLA-B18+ and B18- patients. Fibrosis progression was significantly faster in HLA-B18+ than in HLA-B18- patients ( P < 0.001) (Figure 1). At univariate analysis, age ( P < 0.001), HLA-B18 haplotype ( P = 0.02) and HIV-RNA viral load overtime ( P < 0.001) were associated with liver disease progression. At multivariate analysis, only age ( P < 0.001) remained independently associated with liver fibrosis progression. Our data suggest a possible association between HLA-B18 and an accelerated liver fibrosis in HIV/HCV coinfected with a long-term follow-up.