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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Prognostic non-invasive biomarkers for all-cause mortality in non-alcoholic fatty liver disease: A systematic review and meta-analysis
Nicole Cianci, Mohsan Subhani, Trevor Hill, Amardeep Khanna, Dong Zheng, Abhishek Sheth, Colin Crooks, Guruprasad P Aithal
Nicole Cianci, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and University of Oxford, Oxford OX3 9DU, United Kingdom
Nicole Cianci, Mohsan Subhani, Trevor Hill, Amardeep Khanna, Abhishek Sheth, Colin Crooks, Guruprasad P Aithal, Nottingham Digestive Diseases NIHR Biomedical Research Centre and the University of Nottingham, Nottingham NG7 2UH, United Kingdom
Amardeep Khanna, King’s Liver Transplant Unit, King's College Hospital, London SE5 9RS, United Kingdom
Amardeep Khanna, NIHR Biomedical Research Center, Freeman Hospital and Newcastle University, Newcastle upon Tyne NE7 7DN, United Kingdom
Amardeep Khanna, Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2GW, United Kingdom
Dong Zheng, School of Medicine, Queen Mary University London, London E1 4NS, United Kingdom
Author contributions: Cianci N contributed to the literature search, article screening, data extraction, data analysis and interpretation, manuscript writing; Subhani M contributed to the literature search, article screening, data extraction, proof reading manuscript; Hill T contributed to the data analysis and interpretation, proof reading manuscript; Khanna A contributed to the article screening, data extraction, proof reading manuscript; Zheng D contributed to the data extraction, proof reading manuscript; Sheth A contributed to the article screening, data extraction, proofreading of final manuscript; Crooks C contributed to the project supervisor, study design, review of progress, manuscript review; and Aithal G contributed to the project supervisor, study design, review of progress, manuscript writing and review.
Conflict-of-interest statement: No conflicts of interest are declared.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Nicole Cianci, MBBS, Academic Clinical Fellow in Gastroenterology, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and University of Oxford, Oxford OX3 9DU, United Kingdom.
nicole.cianci@nhs.net
Received: December 9, 2021
Peer-review started: December 9, 2021
First decision: February 15, 2022
Revised: February 28, 2022
Accepted: April 9, 2022
Article in press: April 9, 2022
Published online: May 27, 2022
Processing time: 165 Days and 16.6 Hours
ARTICLE HIGHLIGHTS
Research background
Non-alcoholic fatty liver disease (NAFLD) represents a growing public health concern, highly prevalent in the general population, and with wide range of disease severity and prognosis.
Research motivation
Some NAFLD patients are at increased risk of morbidity and mortality, so it’s important to validate non-invasive prognostic markers for predicting mortality in these patients, to guide risk stratification and more intense clinical focus on high risk patients.
Research objectives
The aim of this systematic review and meta-analysis was to evaluate available evidence on the use of non-invasive test(s) as prognostic factors for mortality in NAFLD.
Research methods
The authors performed electronic searches of Medline and EMBASE (Ovid) until 7th January 2021 of studies in NAFLD populations. We conducted a meta-analysis of non-invasive scoring systems for predicting all-cause and cardiovascular mortality, calculating pooled hazard ratios and 95% confidence (STATA 16.1).
Research results
The authors identified multiple individual non-invasive biomarkers and imaging modality that had a prognostic value in NAFLD patients. Non-invasive scoring systems were the only marker to have been studied in a sufficient number of studies to permit meta-analysis. The non-invasive scoring system that performed best at predicting all-cause mortality was NAFLD fibrosis score (NFS) [pHR 3.07 (1.62-5.83)], followed by fibrosis-4 index (FIB-4) [pHR 3.06 (1.54-6.07)], BARD [pHR 2.87 (1.27-6.46)], and AST to platelet ratio index [pHR 1.90 (1.32-2.73)]. NFS was also prognostic of cardiovascular-related mortality [pHR 3.09 (1.78-5.34)].
Research conclusions
This study reaffirms that non-invasive scoring systems, especially NFS, are reliable prognostic markers of all-cause mortality and cardiovascular mortality in NAFLD patients. Further, we have identified multiple individual biomarkers and imaging modalities that have prognostic value.
Research perspectives
NFS and FIB-4 may be of value in clinical practice in risk-stratification of NAFLD patients with highest risk of mortality. Several other individual serum and imaging markers identified by this systematic review could be studied further to evaluate and validate their prognostic ability.
