Systematic Reviews
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. May 27, 2022; 14(5): 1025-1037
Published online May 27, 2022. doi: 10.4254/wjh.v14.i5.1025
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
Abstract
BACKGROUND

Non-alcoholic fatty liver disease (NAFLD) represents a growing public health concern, with patients having higher risk of morbidity and mortality. It has a considerably high prevalence in the general population, estimated 20%-40% in Europe, and is asymptomatic until late in the disease course. It is therefore important to identify and validate tools that predict hard outcomes such as mortality for use in clinical practice in risk-stratifying NAFLD patients.

AIM

To evaluate available evidence on the use of non-invasive test(s) as prognostic factors for mortality in NAFLD.

METHODS

We performed electronic searches of Medline and EMBASE (Ovid) until 7th January 2021 of studies in NAFLD populations. Prognostic markers included serum biomarkers, non-invasive scoring systems, and non-invasive imaging. The population included all spectrums of disease severity, including NAFLD and non-alcoholic steatohepatitis (NASH). Outcomes included all-cause, and cardiovascular mortality. All non-invasive tests were synthesised in a narrative systematic review. Finally, 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).

RESULTS

Database searches identified 2850 studies – 24 were included. 16 studies reported non-invasive scoring systems, 10 studies reported individual biomarkers, and 1 study reported imaging modalities. 4 studies on non-invasive scoring systems (6324 participants) had data available for inclusion in the 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 [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)].

CONCLUSION

This study reaffirms that non-invasive scoring systems, especially NFS, are reliable prognostic markers of all-cause mortality and cardiovascular mortality in NAFLD patients. These findings can inform clinical practice in risk stratifying NAFLD patients.

Keywords: Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Biomarkers; Non-invasive; Prognosis; Mortality

Core Tip: Non-alcoholic fatty liver disease (NAFLD) represents a growing public health concern, with an estimated prevalence in European general populations of 20%-40% and epidemiological projections of significant future increase in prevalence. NAFLD patients are at increased risk of morbidity and mortality, so it’s important to validate non-invasive prognostic markers for predicting mortality in NAFLD. This systematic review highlighted several non-invasive prognostic markers including biomarkers and imaging modalities. This meta-analysis showed that NAFLD fibrosis score is a useful prognostic marker for all-cause and cardiovascular mortality, which can be implemented in clinical practice to risk stratify and target high risk NAFLD patients.