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      Prognostic accuracy of FIB‐4, NAFLD fibrosis score and APRI for NAFLD‐related events: A systematic review

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          Abstract

          Background & Aims

          Fibrosis is the strongest predictor for long‐term clinical outcomes among patients with non‐alcoholic fatty liver disease (NAFLD). There is growing interest in employing non‐invasive methods for risk stratification based on prognosis. FIB‐4, NFS and APRI are models commonly used for detecting fibrosis among NAFLD patients. We aimed to synthesize existing literature on the ability of these models in prognosticating NAFLD‐related events.

          Methods

          A sensitive search was conducted in two medical databases to retrieve studies evaluating the prognostic accuracy of FIB‐4, NFS and APRI among NAFLD patients. Target events were change in fibrosis, liver‐related event and mortality. Two reviewers independently performed reference screening, data extraction and quality assessment (QUAPAS tool).

          Results

          A total of 13 studies (FIB‐4:12, NFS: 11, APRI: 10), published between 2013 and 2019, were retrieved. All studies were conducted in a secondary or tertiary care setting, with follow‐up ranging from 1 to 20 years. All three markers showed consistently good prognostication of liver‐related events (AUC from 0.69 to 0.92). For mortality, FIB‐4 (AUC of 0.67‐0.82) and NFS (AUC of 0.70‐0.83) outperformed APRI (AUC of 0.52‐0.73) in all studies. All markers had inconsistent performance for predicting change in fibrosis stage.

          Conclusions

          FIB‐4, NFS, and APRI have demonstrated ability to risk stratify patients for liver‐related morbidity and mortality, with comparable performance to a liver biopsy, although more head‐to‐head studies are needed to validate this. More refined models to prognosticate NAFLD‐events may further enhance performance and clinical utility of non‐invasive markers.

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          Most cited references45

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          QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies.

          In 2003, the QUADAS tool for systematic reviews of diagnostic accuracy studies was developed. Experience, anecdotal reports, and feedback suggested areas for improvement; therefore, QUADAS-2 was developed. This tool comprises 4 domains: patient selection, index test, reference standard, and flow and timing. Each domain is assessed in terms of risk of bias, and the first 3 domains are also assessed in terms of concerns regarding applicability. Signalling questions are included to help judge risk of bias. The QUADAS-2 tool is applied in 4 phases: summarize the review question, tailor the tool and produce review-specific guidance, construct a flow diagram for the primary study, and judge bias and applicability. This tool will allow for more transparent rating of bias and applicability of primary diagnostic accuracy studies.
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            Design and validation of a histological scoring system for nonalcoholic fatty liver disease.

            Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of a history of significant alcohol use or other known liver disease. Nonalcoholic steatohepatitis (NASH) is the progressive form of NAFLD. The Pathology Committee of the NASH Clinical Research Network designed and validated a histological feature scoring system that addresses the full spectrum of lesions of NAFLD and proposed a NAFLD activity score (NAS) for use in clinical trials. The scoring system comprised 14 histological features, 4 of which were evaluated semi-quantitatively: steatosis (0-3), lobular inflammation (0-2), hepatocellular ballooning (0-2), and fibrosis (0-4). Another nine features were recorded as present or absent. An anonymized study set of 50 cases (32 from adult hepatology services, 18 from pediatric hepatology services) was assembled, coded, and circulated. For the validation study, agreement on scoring and a diagnostic categorization ("NASH," "borderline," or "not NASH") were evaluated by using weighted kappa statistics. Inter-rater agreement on adult cases was: 0.84 for fibrosis, 0.79 for steatosis, 0.56 for injury, and 0.45 for lobular inflammation. Agreement on diagnostic category was 0.61. Using multiple logistic regression, five features were independently associated with the diagnosis of NASH in adult biopsies: steatosis (P = .009), hepatocellular ballooning (P = .0001), lobular inflammation (P = .0001), fibrosis (P = .0001), and the absence of lipogranulomas (P = .001). The proposed NAS is the unweighted sum of steatosis, lobular inflammation, and hepatocellular ballooning scores. In conclusion, we present a strong scoring system and NAS for NAFLD and NASH with reasonable inter-rater reproducibility that should be useful for studies of both adults and children with any degree of NAFLD. NAS of > or =5 correlated with a diagnosis of NASH, and biopsies with scores of less than 3 were diagnosed as "not NASH."
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              Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention

              NAFLD is one of the most important causes of liver disease worldwide and will probably emerge as the leading cause of end-stage liver disease in the coming decades, with the disease affecting both adults and children. The epidemiology and demographic characteristics of NAFLD vary worldwide, usually parallel to the prevalence of obesity, but a substantial proportion of patients are lean. The large number of patients with NAFLD with potential for progressive liver disease creates challenges for screening, as the diagnosis of NASH necessitates invasive liver biopsy. Furthermore, individuals with NAFLD have a high frequency of metabolic comorbidities and could place a growing strain on health-care systems from their need for management. While awaiting the development effective therapies, this disease warrants the attention of primary care physicians, specialists and health policy makers.
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                Author and article information

                Contributors
                j.a.lee@amsterdamumc.nl
                Journal
                Liver Int
                Liver Int
                10.1111/(ISSN)1478-3231
                LIV
                Liver International
                John Wiley and Sons Inc. (Hoboken )
                1478-3223
                1478-3231
                19 January 2021
                February 2021
                : 41
                : 2 ( doiID: 10.1111/liv.v41.2 )
                : 261-270
                Affiliations
                [ 1 ] Epidemiology and Data Science Amsterdam UMC University of Amsterdam Amsterdam The Netherlands
                [ 2 ] Hepato‐Gastroenterology Department Angers University Hospital Angers France
                [ 3 ] HIFIH Laboratory UPRES EA3859 Angers University Angers France
                [ 4 ] Medical Library Amsterdam UMC University of Amsterdam Amsterdam The Netherlands
                [ 5 ] Cochrane Netherlands Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht University Utrecht The Netherlands
                [ 6 ] The Newcastle Liver Research Group Faculty of Medical Sciences Newcastle University Newcastle upon Tyne UK
                [ 7 ] Newcastle NIHR Biomedical Research Centre Newcastle upon Tyne Hospitals NHS Foundation Trust Newcastle upon Tyne UK
                Author notes
                [*] [* ] Correspondence

                Jenny Lee, Epidemiology and Data Science, Amsterdam UMC, Location AMC, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands.

                Email: j.a.lee@ 123456amsterdamumc.nl

                Author information
                https://orcid.org/0000-0003-4024-0933
                https://orcid.org/0000-0001-7002-118X
                https://orcid.org/0000-0002-9518-0088
                Article
                LIV14669
                10.1111/liv.14669
                7898346
                32946642
                8e3ab308-49b8-405b-a344-c6de44ce1094
                © 2020 The Authors. Liver International published by John Wiley & Sons Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 31 July 2020
                : 27 August 2020
                : 07 September 2020
                Page count
                Figures: 2, Tables: 2, Pages: 10, Words: 6864
                Funding
                Funded by: Innovative Medicines Initiative , open-funder-registry 10.13039/501100010767;
                Award ID: 777377
                Categories
                Original Article
                Reviews & Meta‐analyses
                Custom metadata
                2.0
                February 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.7 mode:remove_FC converted:22.02.2021

                Gastroenterology & Hepatology
                biomarker,non‐alcoholic fatty liver disease,prognostic accuracy

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