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      Uncovering the NAFLD burden in people living with HIV from high‐ and middle‐income nations: a meta‐analysis with a data gap from Subsaharan Africa

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          Abstract

          Introduction

          Non‐alcoholic fatty liver disease (NAFLD) has become a significant concern among people living with HIV (PLHIV), albeit its burden remains unclear. The primary objective of this systematic review (SR) and meta‐analysis (MA) was to estimate the prevalence of NAFLD and significant fibrosis in PLHIV. The secondary objective was to determine the risk factors for NAFLD among PLHIV.

          Methods

          We searched MEDLINE and Scopus from inception to 30 December 2022 for peer‐reviewed studies that included PLHIV and reported the prevalence of NAFLD. MA of proportions was used to estimate the pooled prevalence of NAFLD and significant fibrosis. MA of pre‐calculated effect estimates examined risk factors for NAFLD in PLHIV.

          Results

          We included 24 articles published between 2009 and 2022, encompassing 6326 PLHIV. The pooled prevalence of NAFLD was 38% (95% CI: 31–45%) with high heterogeneity ( I 2 = 96.3%). The pooled prevalence of significant fibrosis was 13% (95% CI: 8–18%) with high heterogeneity ( I 2 = 92.09%). Subgroup analyses showed a NAFLD prevalence of 40% (95% CI: 24–57%) in the United States, 33% (95% CI: 31–36) in Asia, 42% (95% CI: 24–61%) in Europe and 33% (95% CI: 29–37) in South America. When stratifying by income level, NAFLD was 39% (95% CI: 31–48) prevalent in PLHIV from high‐income economies and 34% in both upper‐middle‐income (95% CI: 31–37%) and lower‐middle‐income economies (95% CI: 28–41%). Higher body mass index (BMI) (OR = 1.32, 95% CI: 1.13–1.55; I 2 = 89.9%), increasing triglycerides (OR = 1.48, 95% CI: 1.22–2.79; I 2 = 27.2%) and dyslipidaemia (OR = 1.89, 95% CI: 1.32–2.71; I 2 = 15.5%) were all associated with higher risk‐adjusted odds of NAFLD in PLHIV.

          Discussion

          The burden of NAFLD and significant fibrosis in PLHIV is significant. Therefore, targeted efforts to screen and diagnose NAFLD in this population are needed. Health services for PLHIV could include ways to target NAFLD risk factors, screen for liver disease and implement interventions to treat those with significant fibrosis or more advanced stages of liver disease. Taking no action to address NAFLD in PLHIV should not be an option.

          Conclusions

          This SR and MA found a 38% NAFLD and 13% significant fibrosis prevalence in PLHIV. Increasing triglyceride levels, higher BMI values and dyslipidaemia were associated with higher risk‐adjusted odds of NAFLD among PLHIV.

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          Most cited references83

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          Rayyan—a web and mobile app for systematic reviews

          Background Synthesis of multiple randomized controlled trials (RCTs) in a systematic review can summarize the effects of individual outcomes and provide numerical answers about the effectiveness of interventions. Filtering of searches is time consuming, and no single method fulfills the principal requirements of speed with accuracy. Automation of systematic reviews is driven by a necessity to expedite the availability of current best evidence for policy and clinical decision-making. We developed Rayyan (http://rayyan.qcri.org), a free web and mobile app, that helps expedite the initial screening of abstracts and titles using a process of semi-automation while incorporating a high level of usability. For the beta testing phase, we used two published Cochrane reviews in which included studies had been selected manually. Their searches, with 1030 records and 273 records, were uploaded to Rayyan. Different features of Rayyan were tested using these two reviews. We also conducted a survey of Rayyan’s users and collected feedback through a built-in feature. Results Pilot testing of Rayyan focused on usability, accuracy against manual methods, and the added value of the prediction feature. The “taster” review (273 records) allowed a quick overview of Rayyan for early comments on usability. The second review (1030 records) required several iterations to identify the previously identified 11 trials. The “suggestions” and “hints,” based on the “prediction model,” appeared as testing progressed beyond five included studies. Post rollout user experiences and a reflexive response by the developers enabled real-time modifications and improvements. The survey respondents reported 40% average time savings when using Rayyan compared to others tools, with 34% of the respondents reporting more than 50% time savings. In addition, around 75% of the respondents mentioned that screening and labeling studies as well as collaborating on reviews to be the two most important features of Rayyan. As of November 2016, Rayyan users exceed 2000 from over 60 countries conducting hundreds of reviews totaling more than 1.6M citations. Feedback from users, obtained mostly through the app web site and a recent survey, has highlighted the ease in exploration of searches, the time saved, and simplicity in sharing and comparing include-exclude decisions. The strongest features of the app, identified and reported in user feedback, were its ability to help in screening and collaboration as well as the time savings it affords to users. Conclusions Rayyan is responsive and intuitive in use with significant potential to lighten the load of reviewers.
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            Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes.

            Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. We estimated the global prevalence, incidence, progression, and outcomes of NAFLD and nonalcoholic steatohepatitis (NASH). PubMed/MEDLINE were searched from 1989 to 2015 for terms involving epidemiology and progression of NAFLD. Exclusions included selected groups (studies that exclusively enrolled morbidly obese or diabetics or pediatric) and no data on alcohol consumption or other liver diseases. Incidence of hepatocellular carcinoma (HCC), cirrhosis, overall mortality, and liver-related mortality were determined. NASH required histological diagnosis. All studies were reviewed by three independent investigators. Analysis was stratified by region, diagnostic technique, biopsy indication, and study population. We used random-effects models to provide point estimates (95% confidence interval [CI]) of prevalence, incidence, mortality and incidence rate ratios, and metaregression with subgroup analysis to account for heterogeneity. Of 729 studies, 86 were included with a sample size of 8,515,431 from 22 countries. Global prevalence of NAFLD is 25.24% (95% CI: 22.10-28.65) with highest prevalence in the Middle East and South America and lowest in Africa. Metabolic comorbidities associated with NAFLD included obesity (51.34%; 95% CI: 41.38-61.20), type 2 diabetes (22.51%; 95% CI: 17.92-27.89), hyperlipidemia (69.16%; 95% CI: 49.91-83.46%), hypertension (39.34%; 95% CI: 33.15-45.88), and metabolic syndrome (42.54%; 95% CI: 30.06-56.05). Fibrosis progression proportion, and mean annual rate of progression in NASH were 40.76% (95% CI: 34.69-47.13) and 0.09 (95% CI: 0.06-0.12). HCC incidence among NAFLD patients was 0.44 per 1,000 person-years (range, 0.29-0.66). Liver-specific mortality and overall mortality among NAFLD and NASH were 0.77 per 1,000 (range, 0.33-1.77) and 11.77 per 1,000 person-years (range, 7.10-19.53) and 15.44 per 1,000 (range, 11.72-20.34) and 25.56 per 1,000 person-years (range, 6.29-103.80). Incidence risk ratios for liver-specific and overall mortality for NAFLD were 1.94 (range, 1.28-2.92) and 1.05 (range, 0.70-1.56).
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              Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

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                Author and article information

                Contributors
                juanmanuel.pericas@vallhebron.cat , juan.pericas@vhir.org
                Journal
                J Int AIDS Soc
                J Int AIDS Soc
                10.1002/(ISSN)1758-2652
                JIA2
                Journal of the International AIDS Society
                John Wiley and Sons Inc. (Hoboken )
                1758-2652
                16 March 2023
                March 2023
                : 26
                : 3 ( doiID: 10.1002/jia2.v26.3 )
                : e26072
                Affiliations
                [ 1 ] Liver Unit, Internal Medicine Department Vall d'Hebron University Hospital Barcelona Spain
                [ 2 ] Vall d'Hebron Institute for Research Barcelona Spain
                [ 3 ] Faculty of Medicine Universitat Autònoma de Barcelona Barcelona Spain
                [ 4 ] HIV Unit, Infectious Disease Department Vall d'Hebron University Hospital Barcelona Spain
                [ 5 ] Metabolic Liver Disease Research Program I. Department of Medicine University Medical Center of the Johannes Gutenberg‐University Mainz Germany
                [ 6 ] Barcelona Institute for Global Health (ISGlobal) Hospital Clínic University of Barcelona Barcelona Spain
                [ 7 ] Faculty of Medicine and Health Sciences University of Barcelona Barcelona Spain
                [ 8 ] CUNY Graduate School of Public Health and Health Policy New York New York USA
                [ 9 ] Centros de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd) Madrid Spain
                Author notes
                [*] [* ] Correspondence: Juan M. Pericàs, Liver Unit, Internal Medicine Department, Vall d'Hebron University Hospital, Ground Floor, Desk 071, Pg de la Vall d'Hebron 119–129, Barcelona 08035, Spain.

                juanmanuel.pericas@ 123456vallhebron.cat , juan.pericas@ 123456vhir.org

                Article
                JIA226072
                10.1002/jia2.26072
                10018385
                36924219
                8d40ad93-b84d-427c-b568-c98c65624218
                © 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 07 September 2022
                : 17 February 2023
                Page count
                Figures: 8, Tables: 3, Pages: 19, Words: 9880
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                March 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.6 mode:remove_FC converted:16.03.2023

                Infectious disease & Microbiology
                nafld,mafld,liver fibrosis,hiv,people living with hiv,hiv epidemiology

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