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      Noninvasive Diagnosis of Nonalcoholic Steatohepatitis and Advanced Liver Fibrosis Using Machine Learning Methods: Comparative Study With Existing Quantitative Risk Scores

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          Abstract

          Background

          Nonalcoholic steatohepatitis (NASH), advanced fibrosis, and subsequent cirrhosis and hepatocellular carcinoma are becoming the most common etiology for liver failure and liver transplantation; however, they can only be diagnosed at these potentially reversible stages with a liver biopsy, which is associated with various complications and high expenses. Knowing the difference between the more benign isolated steatosis and the more severe NASH and cirrhosis informs the physician regarding the need for more aggressive management.

          Objective

          We intend to explore the feasibility of using machine learning methods for noninvasive diagnosis of NASH and advanced liver fibrosis and compare machine learning methods with existing quantitative risk scores.

          Methods

          We conducted a retrospective analysis of clinical data from a cohort of 492 patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD), NASH, or advanced fibrosis. We systematically compared 5 widely used machine learning algorithms for the prediction of NAFLD, NASH, and fibrosis using 2 variable encoding strategies. Then, we compared the machine learning methods with 3 existing quantitative scores and identified the important features for prediction using the SHapley Additive exPlanations method.

          Results

          The best machine learning method, gradient boosting (GB), achieved the best area under the curve scores of 0.9043, 0.8166, and 0.8360 for NAFLD, NASH, and advanced fibrosis, respectively. GB also outperformed 3 existing risk scores for fibrosis. Among the variables, alanine aminotransferase (ALT), triglyceride (TG), and BMI were the important risk factors for the prediction of NAFLD, whereas aspartate transaminase (AST), ALT, and TG were the important variables for the prediction of NASH, and AST, hyperglycemia (A 1c), and high-density lipoprotein were the important variables for predicting advanced fibrosis.

          Conclusions

          It is feasible to use machine learning methods for predicting NAFLD, NASH, and advanced fibrosis using routine clinical data, which potentially can be used to better identify patients who still need liver biopsy. Additionally, understanding the relative importance and differences in predictors could lead to improved understanding of the disease process as well as support for identifying novel treatment options.

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          Most cited references30

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          Index for rating diagnostic tests

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            A Unified Approach to Interpreting Model Predictions

            Understanding why a model makes a certain prediction can be as crucial as the prediction's accuracy in many applications. However, the highest accuracy for large modern datasets is often achieved by complex models that even experts struggle to interpret, such as ensemble or deep learning models, creating a tension between accuracy and interpretability. In response, various methods have recently been proposed to help users interpret the predictions of complex models, but it is often unclear how these methods are related and when one method is preferable over another. To address this problem, we present a unified framework for interpreting predictions, SHAP (SHapley Additive exPlanations). SHAP assigns each feature an importance value for a particular prediction. Its novel components include: (1) the identification of a new class of additive feature importance measures, and (2) theoretical results showing there is a unique solution in this class with a set of desirable properties. The new class unifies six existing methods, notable because several recent methods in the class lack the proposed desirable properties. Based on insights from this unification, we present new methods that show improved computational performance and/or better consistency with human intuition than previous approaches. To appear in NIPS 2017
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              Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection.

              Liver biopsy remains the gold standard in the assessment of severity of liver disease. Noninvasive tests have gained popularity to predict histology in view of the associated risks of biopsy. However, many models include tests not readily available, and there are limited data from patients with HIV/hepatitis C virus (HCV) coinfection. We aimed to develop a model using routine tests to predict liver fibrosis in patients with HIV/HCV coinfection. A retrospective analysis of liver histology was performed in 832 patients. Liver fibrosis was assessed via Ishak score; patients were categorized as 0-1, 2-3, or 4-6 and were randomly assigned to training (n = 555) or validation (n = 277) sets. Multivariate logistic regression analysis revealed that platelet count (PLT), age, AST, and INR were significantly associated with fibrosis. Additional analysis revealed PLT, age, AST, and ALT as an alternative model. Based on this, a simple index (FIB-4) was developed: age ([yr] x AST [U/L]) / ((PLT [10(9)/L]) x (ALT [U/L])(1/2)). The AUROC of the index was 0.765 for differentiation between Ishak stage 0-3 and 4-6. At a cutoff of 3.25 had a positive predictive value of 65% and a specificity of 97%. Using these cutoffs, 87% of the 198 patients with FIB-4 values outside 1.45-3.25 would be correctly classified, and liver biopsy could be avoided in 71% of the validation group. In conclusion, noninvasive tests can accurately predict hepatic fibrosis and may reduce the need for liver biopsy in the majority of HIV/HCV-coinfected patients.
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                Author and article information

                Contributors
                Journal
                JMIR Med Inform
                JMIR Med Inform
                JMI
                JMIR Medical Informatics
                JMIR Publications (Toronto, Canada )
                2291-9694
                June 2022
                6 June 2022
                : 10
                : 6
                : e36997
                Affiliations
                [1 ] Department of Health Outcomes & Biomedical Informatics College of Medicine University of Florida Gainesville, FL United States
                [2 ] Target RWE Health Evidence Solutions Durham, NC United States
                [3 ] Department of Medicine College of Medicine University of Florida Gainesville, FL United States
                [4 ] Division of Endocrinology, Diabetes and Metabolism Department of Medicine University of Alabama at Birmingham Birmingham, AL United States
                Author notes
                Corresponding Author: William T Donahoo Troy.Donahoo@ 123456medicine.ufl.edu
                Author information
                https://orcid.org/0000-0002-6780-6135
                https://orcid.org/0000-0003-2981-3972
                https://orcid.org/0000-0002-7540-5315
                https://orcid.org/0000-0002-3371-4582
                https://orcid.org/0000-0003-4903-1804
                https://orcid.org/0000-0002-8629-418X
                https://orcid.org/0000-0001-5570-4396
                https://orcid.org/0000-0002-2126-860X
                Article
                v10i6e36997
                10.2196/36997
                9210198
                35666557
                319b893d-1458-4500-91ab-21f06db5418c
                ©Yonghui Wu, Xi Yang, Heather L Morris, Matthew J Gurka, Elizabeth A Shenkman, Kenneth Cusi, Fernando Bril, William T Donahoo. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 06.06.2022.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Medical Informatics, is properly cited. The complete bibliographic information, a link to the original publication on https://medinform.jmir.org/, as well as this copyright and license information must be included.

                History
                : 2 February 2022
                : 27 March 2022
                : 22 April 2022
                Categories
                Original Paper
                Original Paper

                machine learning,nonalcoholic fatty liver disease,nonalcoholic steatohepatitis,fatty liver,liver fibrosis

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