Introduction
Metabolic dysfunction–associated steatotic liver disease (MASLD) is a growing global health concern, affecting an estimated 25% of the population worldwide [
1]. Early and accurate diagnosis of MASLD is crucial for implementing effective treatment and management strategies, as the disease can progress to more severe conditions such as cirrhosis and liver cancer.
Traditionally, diagnosis of MASLD has relied on imaging techniques such as ultrasound, liver function tests, and biopsy [
2]. However, these methods can be subjective, prone to inter-observer variability, and time-consuming [
3]. Furthermore, sole liver function tests cannot confirm the diagnosis of MASLD due to the indirect measure, and it can be influenced by other factors such as medication use; it usually should be interpreted by a healthcare professional in the context of the individual’s medical history and additional clinical information. Ultrasound may not provide enough detail to accurately diagnose MASLD, particularly in the early stages of the disease; it is also limited in its ability to differentiate between fatty liver and other liver diseases, leading to misdiagnosis or overdiagnosis of MASLD; the results of an ultrasound can be affected by multi-factors such as patient’s weight and the presence of bowel gas, which also limit the accuracy of the scan. In addition, a biopsy is an invasive procedure with associated risks, e.g., infection, and a biopsy is not always available or accessible in all locations, which limits its widespread use for diagnosing MASLD.
In recent years, machine learning (ML) methods have been proposed as a promising alternative for predicting MASLD [
4]. ML algorithms can analyze large amounts of data and identify complex patterns that might not be obvious to human observers. This can lead to more accurate predictions of MASLD and improved risk stratification and personalized treatment approaches. Several types of ML algorithms exist, including supervised, unsupervised, semi-supervised, and reinforcement learning [
5]. Supervised learning algorithms, e.g., k-nearest neighbors (KNN), support vector machines (SVM), logistic regression (LR), and artificial neural networks (ANN), are the most common ones, and they can be used for both classification and regression [
6].
In the context of MASLD, early detection and accurate diagnosis are crucial for effective management. This is where ML can play a significant role. By leveraging advanced computational techniques, ML algorithms can analyze large and complex datasets to make predictions about MASLD. In this study, we aimed to evaluate the performance of these algorithms in detecting MASLD and assess their potential as a diagnostic tool. The results of this research will contribute to a better understanding of the utility of ML in MASLD diagnosis and pave the way for more effective and efficient diagnostic methods.
Discussion
ML models were applied to predict the occurrence of MASLD based on a large sample in a cross-sectional study performed with subjects who attended a health examination at the Pudong District Health Care Service Centers in the Zhangjiang area of Shanghai, China. We used ML variable selection methods to screen for risk factors for MASLD. Of the 44 extracted variables, seven variables were selected based on the fivefold and tenfold CV from ML models in the discovery set and our prior knowledge, which included BMI, albumin, ALT, glucose, HDL, TG, and creatinine. Notably, the AUCs, MCC, and precision of the 7-variable set using KNN, SVC, and ANN models were significantly higher compared to the all-variable set in the independent test set, which indicates that the performance in the independent test set was much better than that in the discovery set, confirming the robustness of the selected 7-variable set.
In the older population, both BMI and waistline were considered essential indicators for predicting the risk of developing MASLD [
15]. However, BMI as an indicator is more common because it is a simpler, quicker, and less invasive method of measuring body composition compared to waistline measurement. In addition, BMI also provides an overall assessment of body fat levels and distribution, which is crucial in determining the risk of developing MASLD and other related health conditions [
16]. Nevertheless, waistline measurement was still considered a valuable tool in assessing the amount of abdominal fat. It is a better predictor of risk for frailty, given its relationship with metabolic disorders in community-dwelling old adults in Beijing [
17]. Therefore, we believe that it depends on the specific condition when BMI or waistline is used as a variable to correlate to MASLD or other metabolic disorders in a particular population.
Albumin was one of the seven predictors and demonstrated high prediction power in this study. Albumin plays a role in the immune system by transporting antibodies and hormones and binding to toxins and waste products [
18]. This helps to remove those harmful substances from the body and maintain a healthy immune response. Regarding MASLD, research has shown a correlation between decreased albumin levels and inflammation aggravation, which can worsen liver disease progression [
19]. This can also indicate advanced stages of MASLD and the presence of liver fibrosis, which can increase the risk of liver failure and other complications. Hence, determining the amount of albumin can aid in diagnosing and keeping track of MASLD and evaluating the advancement and response to therapy. The relationship between albumin and TG in MASLD was not well established. However, low albumin levels have generally been associated with higher levels of TG and other markers of insulin resistance, which were known risk factors for MASLD [
20].
It is worth noting that the accumulation of TG, common in obese and lean individuals with MASLD, can cause inflammation and oxidative stress, leading to liver damage [
21]. The TG, glucose, and BMI combination in the TG-glucose-BMI index was considered better for predicting MASLD than using any of these variables alone, as they provide a more comprehensive assessment of metabolic health and the risk of developing the liver disease [
22,
23]. This index considers lipid metabolism, glucose metabolism, and body fat distribution critical factors in MASLD’s development and progression. In our study, besides including the three variables mentioned earlier, adding more indicators, i.e., albumin, ALT, HDL, and creatinine, that can reflect metabolic and inflammatory characteristics can improve the prediction of MASLD and monitor changes in metabolic health over time.
ALT was generally considered a more reliable marker for MASLD compared to AST and was often included in studies of MASLD as a predictor or diagnostic tool [
24]. ALT and AST are both liver enzymes commonly used as liver injury markers. However, ALT was considered a more specific indicator of liver damage than AST, as ALT is primarily found in the liver, and elevated levels indicate liver disease [
25], which was consistent with our study. In contrast, AST was found in other organs as well, and elevated AST levels can also indicate diseases or conditions in other organs, such as the skeletal muscle [
26]. It is important to note that the choice of which liver enzyme to include in a study relies on the specific goals of the study, as well as the type of population being studied and the availability of data.
Cholesterol is not always included as a predictor of MASLD because it is not a direct marker of liver inflammation or damage [
27]. While elevated cholesterol levels can be associated with an increased risk of cardiovascular disease and other health problems, it is not a specific marker for MASLD [
28]. Specifically, cholesterol is a more general marker of metabolic health and is influenced by various factors such as diet and genetics [
29,
30]. This can make it less specific to MASLD. Additionally, the subtypes of cholesterol, such as HDL and LDL, can have different health effects. HDL is often included as a predictor or diagnostic marker for MASLD as it has been shown to have a protective effect against the development of liver disease [
30,
31]. The choice of HDL in this study as one of the predictor variables in ML models was based on the results of statistical analyses and the ability of the variables to predict the outcome of interest.
Notably, creatinine was also included in the prediction of MASLD in this study. Creatinine is a waste product produced by muscle metabolism and is typically excreted by the kidneys [
32]. Creatinine levels vary depending on several factors, including age, muscle mass, and kidney function [
33]. In the older population, creatinine levels can increase due to decreased muscle mass and a decline in kidney function [
34]. The relationship between creatinine levels and muscle metabolism is complex, but creatinine levels are believed to reflect muscle mass and its metabolic activity. High creatinine levels can indicate decreased kidney function and muscle wasting, which can be relevant in the context of MASLD [
35]. NASH patients had significantly more elevated serum creatinine than those with other chronic liver diseases [
36,
37]. Therefore, creatinine levels can be an essential factor to consider in evaluating individuals with suspected or confirmed MASLD, as they provide additional information about overall health status and the potential presence of comorbid conditions.
When predicting MASLD using ML, a smaller set of variables, such as the seven commonly selected ones (i.e., BMI, albumin, ALT, glucose, HDL, TG, and creatinine), can have several advantages in this study. Firstly, a smaller number of variables can make the prediction model more manageable and easier to work with, as it reduces the complexity of the model and the risk of overfitting. Secondly, these selected seven variables have been found to have strong associations with MASLD and be good predictors of the disease in numerous studies. Thirdly, more minor variables can make the model more interpretable and transparent. Understanding the relationships between the variables and the outcome of interest can be more accessible. In summary, while using all available variables might provide more information, the trade-off is increased complexity and increased risk of overfitting. Using a carefully selected subset of variables can give a more robust and usable model for predicting MASLD [
38].
Notably, Chen et al
. [
39] reported that the xgBoost model had the best overall prediction ability for diagnosing FLD with the highest AUC (0.882) in Taiwanese subjects. Su et al
. [
40] found that the two-class neural network exhibited a higher AUC value for predicting fatty liver (0.868) in Korean population. In our study, the AUCs of the 7-variable set using KNN (0.833), SVC (0.753), and ANN (0.848) models were significantly higher compared to the all-variable set in the independent test set, all of which suggest that ML algorithms offer benefits for screening MASLD, although these studies used different algorithms. This also shows that the same predictive model may not be suitable for other patients or ethnic groups. Additionally, although fatty liver index (FLI) is regarded as a suitable and simple predictor for liver steatosis, Motamed et al
. [
41] reported that the performance of FLI in predicting MASLD in the Iran population was not more effective than waist circumference. Su et al
. [
40] observed that ML method has the higher predictive ability than FLI in the Korean population. So a modified FLI formula based on different ethical populations is necessary.
The limitations of this study included the small sample size, being limited to data from one center, and the lack of external validation. The prediction model was based on electronic medical records that may contain inherent biases but are readily accessible and the most practical option for predicting MASLD. Additionally, the biopsy is the gold standard of MASLD diagnosis; instead, we used color ultrasound to diagnose MASLD in this study due to its low cost. Despite these limitations, the proposed combination of variable selection and ML approach is still noteworthy for the early prediction of MASLD. Our study is based on the elderly population in the community, which is indicative of the prevention and treatment of MASLD in this special population. More clinical data from various centers operating under varied ethical standards are required to further validate the model’s predictions.
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