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OPEN Application of machine learning

in predicting non‑alcoholic fatty
liver disease using anthropometric
and body composition indices
Farkhondeh Razmpour 1,10*, Reza Daryabeygi‑Khotbehsara 2,10*, Davood Soleimani 3,
Hamzeh Asgharnezhad 4, Afshar Shamsi 5,6, Ghasem Sadeghi Bajestani 7, Mohsen Nematy 8,
Mahdiyeh Razm Pour 9, Ralph Maddison 2 & Sheikh Mohammed Shariful Islam 2

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, which can
progress from simple steatosis to advanced cirrhosis and hepatocellular carcinoma. Clinical diagnosis
of NAFLD is crucial in the early stages of the disease. The main aim of this study was to apply machine
learning (ML) methods to identify significant classifiers of NAFLD using body composition and
anthropometric variables. A cross-sectional study was carried out among 513 individuals aged 13 years
old or above in Iran. Anthropometric and body composition measurements were performed manually
using body composition analyzer InBody 270. Hepatic steatosis and fibrosis were determined using
a Fibroscan. ML methods including k-Nearest Neighbor (kNN), Support Vector Machine (SVM),
Radial Basis Function (RBF) SVM, Gaussian Process (GP), Random Forest (RF), Neural Network (NN),
Adaboost and Naïve Bayes were examined for model performance and to identify anthropometric and
body composition predictors of fatty liver disease. RF generated the most accurate model for fatty
liver (presence of any stage), steatosis stages and fibrosis stages with 82%, 52% and 57% accuracy,
respectively. Abdomen circumference, waist circumference, chest circumference, trunk fat and body
mass index were among the most important variables contributing to fatty liver disease. ML-based
prediction of NAFLD using anthropometric and body composition data can assist clinicians in decision
making. ML-based systems provide opportunities for NAFLD screening and early diagnosis, especially
in population-level and remote areas.

Abbreviations
NAFLD Non-alcoholic fatty liver disease
BMI Body mass index
LSM Liver stiffness measurement
ROCc Receiver operating characteristic curve
PCA Principal component analysis
CAP Controlled attenuation parameter
CI Confidence interval
ANOVA Analysis of variance
DCL Dorso-cervical lipohypertrophy

1
Department of Nutrition, Faculty of Medicine, Hormozgan University of Medical Sciences, Shahid Chamran
Boulevard, Bandar Abbas, Iran. 2Institute for Physical Activity and Nutrition (IPAN), Deakin University, Geelong
Victoria, Australia. 3Department of Nutrition, School of Nutrition Sciences and Food Technology, Kermanshah
University of Medical Sciences, Kermanshah, Iran. 4Institute for Intelligent Systems Research and Innovation
(IISRI), Geelong Waurn Ponds Victoria, Australia. 5Biomedical Machine Learning Lab, University of New South
Whales, Sydney, Australia. 6Concordia Institute for Information Systems Engineering, Concordia University,
Montreal, Canada. 7Department of Biomedical Engineering, Faculty of Engineering, Imam Reza International
University, Mashhad, Iran. 8Metabolic Syndrome Research Center, Faculty of Medicine, Mashhad University of
Medical Sciences, Mashhad, Iran. 9Department of Electronic Learning, Shiraz University, Shiraz, Iran. 10These
authors contributed equally: Farkhondeh Razmpour and Reza Daryabeygi-Khotbehsara. *email: frazmpoor@
gmail.com; reza.d@deakin.edu.au

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Non-alcoholic fatty liver disease (NAFLD)‒ the hepatic manifestation of metabolic syndrome‒ is the most
common chronic liver d ­ isease1,2. Worldwide prevalence of metabolic syndrome and NAFLD has increased in
parallel with increased obesity ­prevalence3–5, which is about 20–30% in developed countries and one-third
among American a­ dults6–8.
Obesity is a common metabolic risk factor associated with ­NAFLD9–11. The prevalence of NAFLD is directly
related to increased body mass index (BMI) and central o ­ besity12–14. Most studies have shown that visceral fat
is an independent factor in generating hepatic steatosis, independent of B ­ MI15,16. The amount of adipose tissue
and its distribution differs between men and ­women17. Women have higher overall fat tissue with relatively more
subcutaneous adipose tissue in the hips and thighs. At the same time, men accumulate visceral and subcutaneous
fat mainly in the trunk and abdomen with continuous changes before and after p ­ uberty17–19. The increased fat
distribution around the waist (i.e. apple-shaped body) is linked to NAFLD in both g­ enders20. In a pear-shaped
body, the subcutaneous fat accumulates mainly in the thighs and b ­ uttocks21,22, which is typical among females
but can increase metabolic syndrome in males, which is a risk factor for NAFLD independent of central o­ besity23.
In support of the role of fat distribution and anthropometric measures in NAFLD, studies have found several
contributing factors, including abdomen circumferences, waist, neck and fat accrual in trunk and ­arms24–29.
Most people with NAFLD, including both children or adults, do not have differential symptoms at the early
stages of the ­disease30. Notably, after the development of cirrhosis, different symptoms such as caput medusa,
spider angioma, palmar erythema, ascites, and jaundice ­appear31. Therefore, early diagnosis is critical to prevent
severe complications.
Ultrasonography and laboratory tests are typical diagnostic methods for detecting fatty liver disease.
Ultrasound technique has relatively high accuracy in detecting the moderate-to-severe steatosis level and lower
accuracy in earlier stages of ­NAFLD32. Notably, hepatic fibrosis cannot be diagnosed by ­ultrasonography14,33.
Although typically used to detect fatty liver disease, laboratory tests are not useful for all ages and gender groups
due to low a­ ccuracy34,35. Therefore, a precise, cost-effective, and non-invasive method to analyze symptoms of
various stages of the fatty liver for NAFLD diagnosis is desirable. Such an approach is important to help with
early diagnosis of NAFLD, which could help prevent hepatic steatosis progression to fibrosis, advanced cirrhosis,
and hepatocellular carcinoma.
In recent years, machine learning (ML) models have been used as a novel approach in predicting ­NAFLD36–39.
However, all of these studies have focused mainly on laboratory outcomes and have not considered body
composition and anthropometric factors. Therefore, the primary aim of this study is to identify essential ML
classifiers of NAFLDs using body composition and anthropometric indices. The secondary aim is to identify
feature contributions to the prediction of NAFLDs.

Materials and methods

Study design and participants. This cross-sectional study was conducted to explore NAFLD phenotypes
based on body composition and anthropometric indices. Participants were recruited from the eastern (Khorasan
Razavi) and southern (Hormozgan) provinces of Iran, through advertisement on the notice boards of the
university clinics, as well as via phone or email contact to potential participants. A total of 593 individuals aged
above 13 years old were initially recruited. Eighty individuals were excluded from the study and 513 participants
were remained. Exclusion criteria were as follows: the presence of underlying liver disease, taking medications
(anti-hypertensive and anti-arrhythmic, anti-glycaemic, corticosteroids, nervous system agents, chemotherapy,
Methotrexate and Tamoxifen), alcoholic patients with more than twice-a-week consumption, previous history of
any type of cancer during the last year, history of surgery during the last 6 months, pregnant women. The study
was conducted following the Declaration of Helsinki, and ethical approval was granted by Mashhad University
of Medical Sciences following (Code: IR.MUMS.fm.REC.1395.64). All participants provided written informed
consent. Also, written informed consent was obtained from guardians of participants aged under 18 years.

Data collection. At each medical clinic, eligibility, demographics questionnaire, anthropometric, and
body composition measurements were assessed by two trained nutritionists. Medical examination and
disease diagnosis were performed by a general physician and an internal specialist, respectively. Demographic
information, including sex, age, education, disease history and medications, were assessed by researcher using a
questionnaire. Weight was measured using a digital weighing scale (Seca 704; Hamburg, Germany), height was
measured using a wall height chart, and the body composition measures were assessed using InBody 270 (Inbody
Co. Ltd, South Korea) body analyzer to measure per cent (%) body fat, total fat mass, muscle mass, as well as fat
mass in the right/left leg, right/left arm and trunk with light clothing and without shoes. The circumferences of
neck, chest, arm, wrist, waist, hips, abdomen, thighs, and length of ulna and leg were measured using a flexible
tape measure with an accuracy of 0.1 cm. BMI was calculated by dividing weight (kilograms) by the height
in meters s­ quared26. Subcutaneous fat in the area below the scapula, arms biceps and triceps and the upper
iliac crest was measured using a Saehan calliper (Saehan SH5020, Korea). Participants were also examined for
acanthosis in the back of the neck and armpits and the presence of subcutaneous fat under the chin and at the
back of the neck. A Fibroscan equipped with the M and XL probes (Echosens 504, Paris, France) was used to
assess both controlled attenuation parameter (CAP) (dB/m) and liver stiffness measurement (LSM) (kPa) values
simultaneously. A reliable LSM was defined as the median liver stiffness of the 10 measurements (a success rate
of greater than 60%, and an IQR < 30% of the median LSM value)40. CAP values range from 100 to 400 dB/m and
the following cut-off values were used for the diagnosis of steatosis stages: Stage 0, < 238 dB/m, Stage 1, ≥ 238 to
260 dB/m, Stage 2, ≥ 260 to 292 dB/m, and Stage 3, ≥ 292 dB/m41. LSM values range from 1.5 to 75 kPa, and the
following cut-off values were used for the diagnosis of liver fibrosis stages: no significant fibrosis or F0 < 6.2 kPa,

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mild fibrosis or F1 ≥ 6.2 to 7.6 kPa, moderate fibrosis or F2 ≥ 7.6 to 8.8 kPa, severe fibrosis or F3 ≥ 8.8 to 11.8 kPa
and cirrhosis or F4 ≥ 11.8 ­kPa42.

Statistical analysis. Descriptive and non-predictive data analysis was performed using SPSS version 21
software (SPSS, Inc., Chicago, IL). Data were expressed as mean ± standard deviation or frequencies. Between-
group comparisons were performed using an independent sample t test and analysis of variance (ANOVA),
followed by Tukey’s post hoc test. A P-value of less than 0.05 was considered statistically significant.

Machine learning models. Three label variables were considered: fatty liver (stage I, II and III vs. no
steatosis), steatosis, and fibrosis stages. Eight ML techniques were applied to the dataset to identify the best
modelling approach. To this end, k-Nearest Neighbor (kNN), Support Vector Machine (SVM), Radial Basis
Function (RBF) SVM, Gaussian Process (GP), Random Forest (RF), Neural Network (NN), AdaBoost and Naïve
Bayes were tested. An extant explanation of these classifiers can be found e­ lsewhere43. Testing of these models
was performed using the Scikit-learn library in Python programming l­anguage44.
To comprehensively compare different classifiers, we trained and evaluated dataset 50 times. This is because
different classifiers sometimes predict slightly different outputs and initial points are different for a specific
classifier in each run. Thus, a reliable output can be estimated by averaging each classifier several times. Model
accuracy and area under the curve (AUC) are reported for each ML technique. Importance values are reported
for individual feature variables.
Pre-processing involved data normalization and segmentation. The few missing values in the numerical results
of the experiments were replaced using the Linear Interpolation ­method45. Principal component analysis (PCA)
was used to extract the attribute of the d ­ ata46,47. Data were divided into two parts, train and test. Processing
involved feature selection and classification with the best feature. The model processing involved a variety of
models. The model with the highest performance was selected.

Patient consent. All patients provided written consent for participation in this study. For participants aged
under 18 years, written informed consent was obtained from their guardians.

Ethics approval. Ethical approval was received from the research ethics committee at Mashhad University
of Medical Sciences (Code: IR.MUMS.fm.REC.1395.64).

Results
In total 513 participants (240 males and 273 females) took part in the study, of whom 169 (74.1%) male and 220
(80.6%) female cases had a degree of hepatic steatosis. The mean age, weight, and BMI were 37.04 ± 15.44 years,
77.26 ± 17.31 kg, and 28.15 ± 4.89 kg ­m2, respectively. Overall demographic characteristics and biochemical
measures are presented in Table 1. Significant differences were found in most anthropometric variables between
male and female participants (see Tables 2 and 3).

Machine learning results. Figures 1, 2, 3 present box plots for each classification method applied to three
outcomes. Random Forest (RF) method generated the most accurate ML model for fatty liver (presence of any
stage), steatosis stage and fibrosis stage. Average accuracy and AUC values resulted from RF were 0.82 and 0.84
for fatty liver, 0.52 and 0.69 for steatosis stages, 0.57 and 0.58 for fibrosis stages, respectively. Average accuracy
and AUC are presented in the Supplemental file (Model Iterations) for all conditions. Moreover, sensitivity,
specificity, true positive and true negative measures were presented for fatty liver disease.
Feature variables with the highest predictability for fatty liver were abdomen circumference (IV; average
importance value = 0.061), waist circumference (IV = 0.061), chest circumference (IV = 0.054), trunk fat
(IV = 0.056) and BMI (IV = 0.053); for steatosis, the stage was abdominal circumference (IV = 0.053), waist
circumference (IV = 0.052), chest circumference (IV = 0.052), trunk fat (IV = 0.051) and BMI (IV = 0.050); and
for fibrosis were abdominal circumference (IV = 0.049), waist circumference (IV = 0.049), chest circumference
(IV = 0.043), BMI (IV = 0.045) and weight (IV = 0.045). See Figs. 4, 5, 6 and Tables 4, 5, 6.
Further assessment identified gender-specific features (see Supplemental Figs. 1–6; Supplemental Tables 1–6).
Important predictor factors for fatty liver disease among females were waist circumference (IV = 0.057), abdomen
circumference (IV = 0.056), trunk fat (IV = 0.055), fat mass (IV = 0.052), chest circumference (IV = 0.048), and
BMI (IV = 0.048) were the most important features. Among males, waist circumference (IV = 0.053), chest
circumference (IV = 0.052), trunk fat (IV = 0.051), BMI (IV = 0.052), abdomen circumference (IV = 0.049) and
fat mass (IV = 0.048) had the highest predictive value for fatty liver. Important predictor factors for steatosis
among females were abdomen circumference (IV = 0.048), waist circumference (IV = 0.047), weight (IV = 0.046),
trunk fat (IV = 0.045), fat mass (IV = 0.044), and BMI (IV = 0.043) were the most important features. Among
males, waist circumference (IV = 0.051), chest circumference (IV = 0.050), abdomen circumference (IV = 0.049),
trunk fat (IV = 0.048), BMI (IV = 0.048), and fat mass (IV = 0.046) had the highest predictive value for steatosis.
Important predictor factors for fibrosis among females were abdomen circumference (IV = 0.048), waist
circumference (IV = 0.047), BMI (IV = 0.046), trunk fat (IV = 0.045), chest circumference (IV = 0.043), and
muscle mass (IV = 0.043) were the most important features. Among males, abdomen circumference (IV = 0.045),
waist circumference (IV = 0.043), weight (IV = 0.043), BMI (IV = 0.043), right arm fat (IV = 0.042) and fat mass
(IV = 0.042) had the highest predictive value for fibrosis.

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Variable N Percentage (%)

Gender
Female 270 52.6
Male 238 46.4
Diabetes
Non-diabetic 442 85.7
Diabetic 66 13.3
Mean ± SD Range
Age (years) 37.04 ± 15.44 9–74
Height (cm) 165.44 ± 11.18 132–189
Weight (kg) 77.26 ± 17.31 27–141
BMI (kg/m2) 28.15 ± 4.89 15–52
Triglyceride (mg/dL) 130.44 ± 77.16 17–563
Total cholesterol (mg/dL) 174.99 ± 42.29 3–301
LDL-cholesterol (mg/dL) 101.28 ± 32.47 48–191
HDL-cholesterol (mg/dL) 43.61 ± 10.19 25–86
Haemoglobin (g/dL) 14.00 ± 1.84 10–24
AST (U/L) 29.98 ± 23.51 6–308
ALT (U/L) 38.28 ± 35.45 5–325
GGT (U/L) 28.29 ± 27.58 6–211
FBS (mg/dL) 96.31 ± 26.46 50–327
HbA1c (%) 5.50 ± 1.80 3–25

Table 1.  Demographic information of study participants. SD standard deviation, cm centimetres, kg

kilograms, BMI body mass index, kg/m2 kilograms per metres squared, mg/dL milligrams per decilitre, g/
dL grams per decilitre, U/L units per litre, AST aspartate aminotransferase, ALT alanine transaminase, GGT​
gamma-glutamyl transferase, FBS fasting blood glucose, HbA1c glycosylated haemoglobin.

Discussion
This study applied ML techniques to determine the optimal body composition and anthropometric classifier
of NAFLD and identify feature contribution to the prediction of the disease. RF generated the most accurate
ML model to predict fatty liver presence, steatosis (stages) and fibrosis. To our knowledge, this is the first
study applying ML on body composition and anthropometric data to predict NAFLD. High accuracy (82%)
highlights the potential for applying ML techniques for the primary prevention and screening of NAFLD using
anthropometric measurements.
Previous studies using ML techniques to predict fatty liver disease have mainly focused on biochemical
measurements, with similar levels of accuracy (83.0%) using Bayesian N ­ etwork38, (76.3%) Logistic R ­ egression37,
(86.4%) ­RF39 and (80%) Classification Tree ­techniques36. However, we tested the predictive value of body
composition and anthropometric measurements rather than biochemical variables. Anthropometry as a lower-
cost and more feasible approach can be considered a primary screening method for fatty liver disease.
Abdominal obesity is a significant risk factor leading to N ­ AFLD27. Waist circumference and trunk fat have
been shown to be significantly predicting the risk of ­NAFLD24. Although BMI is one of the risk factors of
­NAFLD31, it has been argued that BMI is limited compared to other anthropometric measures (e.g., waist
circumference) in identifying lean NAFLD i­ ndividuals25. In a similar vein, the findings of the present study clearly
show the importance of these body composition and anthropometric measures and their relative contribution
to the prediction of NAFLD.
Neck circumference reflects the amount of subcutaneous fat in the upper body, and is a reliable factor in
determining central o ­ besity48. A positive correlation has been shown between neck circumference and hepatic
26,28
­steatosis . Neck circumference showed a positive association with other anthropometric components, such
as BMI and waist and waist-to-hip circumference. In the present study, neck circumference contributed almost
equally to hepatic steatosis and fibrosis.
A study by Subramanian revealed that the level of arm fat index in both males and females had a negative
association with the degree and severity of ­NAFLD29. In our study, a strong and positive relationship between
arm circumference and the severity of steatosis and fibrosis was detected, validated by the ML model. Rafiee et al.
showed that the amount of fat in hips and legs and circumference of hip negatively associated with fatty liver
and the severity of the disease. In contrast, the waist-to-hip ratio was closely associated with fatty liver. They also
showed that the accuracy of this ratio in predicting NAFLD was greater than BMI and waist-to-height ­ratio49.
Most ML studies for the prediction of NAFLD have used the ultrasonography technique to diagnose fatty liver
­disease36–39. Ultrasound is a commonly used method for the diagnosis of hepatic ­steatosis50. Ultrasonography
is a safe, well-tolerated, non-invasive and low-cost ­technique50; however, there are limitations associated with
ultrasound use, including limited capability in detecting fatty infiltration (less than 20% steatosis), operator
dependency and subjective a­ ssessment51,52, and ML is expected to minimise some of these. Application of ML

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Hepatic Steatosis
Variables Gender Grade 0 Grade Ι Grade ΙΙ Grade ΙΙΙ P-value
F 53 39 55 129 –
Number
M 81 38 48 77 –
F 31.13 ± 15.79# 34.64 ± 16.67 42.02 ± 15.37# 41.79 ± 15.88# 0.001
Age, years
M 27.54 ± 12.32 35.51 ± 19.29 39.33 ± 13.91# 36.12 ± 13.68# 0.001
F 59.90 ± 11.40 67.09 ± 11.08# 69.26 ± 11.24# 79.93 ± 14.56#&$ < 0.001
Weight; kg
M 66.71 ± 13.59 75.69 ± 13.90# 82.56 ± 10.39# 87.84 ± 16.70#& < 0.001
F 156.84 ± 8.46 158.64 ± 8.04 155.83 ± 7.68 159.00 ± 6.94 0.206
Height; cm
M 167.50 ± 13.60 167.78 ± 13.47 171.23 ± 6.68 172.15 ± 8.99 0.31
F 24.30 ± 4.00 26.53 ± 3.16 28.45 ± 3.44# 31.60 ± 5.21#&$ < 0.001
BMI; kg ­m−2
M 23.83 ± 3.21 26.86 ± 3.21# 28.19 ± 3.53# 29.67 ± 4.03#& < 0.001
F 27.60 ± 3.53 29.74 ± 3.14# 31.30 ± 2.58# 33.44 ± 4.23#&$ < 0.001
Arm circumference; cm
M 28.81 ± 3.04 30.51 ± 2.70 31.90 ± 2.53# 33.27 ± 3.47#& < 0.001
F 31.68 ± 2.37 32.77 ± 1.65 33.25 ± 1.89# 35.70 ± 2.34#&$ < 0.001
Neck circumference; cm
M 36.09 ± 2.83 37.80 ± 2.73 38.94 ± 2.87# 39.56 ± 2.87#& < 0.001
F 89.04 ± 8.79 94.30 ± 8.19# 98.78 ± 7.61# 106.18 ± 9.56#&$ < 0.001
Chest circumference; cm
M 89.32 ± 10.24 96.78 ± 10.43# 101.34 ± 7.52# 104.26 ± 10.86#& < 0.001
F 81.74 ± 10.85 86.69 ± 7.25 94.57 ± 7.92#& 101.96 ± 10.53#&$ < 0.001
Waist circumference; cm
M 85.71 ± 9.08 96.42 ± 7.99# 99.83 ± 8.75# 102.68 ± 10.07#& < 0.001
F 85.82 ± 11.11 91.77 ± 7.60# 98.15 ± 7.70# 105.33 ± 10.52#&$ < 0.001
Abdomen circumference; cm
M 87.61 ± 8.88 98.50 ± 7.12# 101.27 ± 8.93# 104.15 ± 9.83#& < 0.001
F 98.03 ± 12.80 101.87 ± 9.20 103.50 ± 8.82 106.60 ± 13.60# 0.002
Hip circumference; cm
M 96.70 ± 8.88 101.31 ± 6.67 103.88 ± 7.21# 106.57 ± 8.00#& < 0.001
F 14.98 ± 0.94 15.63 ± 0.742 15.78 ± 1.13# 16.30 ± 1.44# < 0.001
Wrist circumference; cm
M 16.71 ± 0.87 17.44 ± 1.11# 17.66 ± 0.85# 17.92 ± 1.10# < 0.001
F 15.40 ± 5.40 19.05 ± 5.19 21.29 ± 4.81# 25.33 ± 9.10#& < 0.001
Subscapular skinfold; mm
M 14.01 ± 5.32 19.58 ± 7.06# 19.56 ± 9.05# 22.93 ± 8.56# < 0.001
F 8.02 ± 3.29 9.47 ± 3.38 9.94 ± 2.48 12.76 ± 5.17#&$ < 0.001
Biceps skinfold; mm
M 6.69 ± 3.65 8.83 ± 3.80 9.01 ± 4.14# 9.34 ± 3.15# 0.001
F 11.22 ± 3.44 14.35 ± 6.19# 14.02 ± 3.75 16.33 ± 6.49# < 0.001
Triceps skinfold; mm
M 9.02 ± 3.71 11.16 ± 5.05 10.40 ± 4.34 11.48 ± 3.98# 0.019
F 14.82 ± 5.27 17.59 ± 6.08 19.26 ± 6.06# 21.30 ± 7.54# < 0.001
Suprailiac skinfold; mm
M 13.98 ± 5.96 18.98 ± 7.35# 16.62 ± 7.41 19.42 ± 7.99# 0.001

Table 2.  A comparison of the anthropometric variables across different stage of the hepatic steatosis in
male and female participants. Abbreviation. BMI: body mass index. Data are presented as means ± standard
deviations. P values were obtained from analysis of variance (ANOVA), followed by Tukey’s post hoc test.
#
Significant difference (P < 0.05) compared with grade 0; &Significant difference (P < 0.05) compared with grade
1; $Significant difference (P < 0.05) compared with grade 2.

techniques on body composition and anthropometric measures as a less time-consuming and easy to undertake
method can help physicians in their clinical decision making.
The presence of liver fibrosis in patients with NAFLD is considered the strongest predictor of long-term
­outcome53. NAFLD Fibrosis Score (NFS) and Fibrosis-4 (FIB-4) have been recommended as appropriate methods
for the initial assessment of fibrosis in NAFLD ­patients54. Both of these methods use a combination of variables
including age, BMI and biochemical measures (i.e. aspartate aminotransferase (AST), alanine aminotransferase
(ALT), platelets, etc.). Graupera et al. concluded that NFS and FIB-4 are not optimal for screening as they
correlate poorly with liver ­stiffness55. In their study, waist circumference was found to be the ideal measure for
fibrosis screening among high risk people from general p ­ opulation55. However, other studies found that NFS and
FIB-4 have the potential to detect advanced fibrosis and the progression of fibrosis among people with N ­ AFLD56.
It seems that NFS and FIB-4 are more useful in the diagnosis of fibrosis in NAFLD but not for fibrosis screening
among the general populations. The present study showed suboptimal accuracy (57%) in detecting fibrosis using
less expensive and non-invasive factors i.e. anthropometric and body composition measures. Further studies
might explore a combination of these methods including anthropometric, body composition and biochemical
variables altogether.

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Hepatic fibrosis
Variables Gender Grade 0 Grade Ι Grade ΙΙ Grade ΙΙΙ–IV P-value
F 137 82 37 17 –
Number
M 156 59 14 15 –
F 34.78 ± 16.36 38.11 ± 17.09 49.33 ± 10.64# 50.12 ± 8.09# 0.005
Age, years
M 33.05 ± 14.87 36.42 ± 14.47 36.02 ± 15.02 42.15 ± 15.30 0.119
F 65.97 ± 12.73 72.39 ± 14.79# 81.56 ± 22.85# 81.77 ± 12.44# < 0.001
Weight; kg # #
M 76.25 ± 14.83 83.92 ± 15.62 90.08 ± 20.44 90.37 ± 18.95# < 0.001
F 157.78 ± 8.53 157.48 ± 6.70 157.55 ± 3.84 156.12 ± 6.49 0.9150
Height; cm
M 169.34 ± 11.82 171.77 ± 8.39 177.08 ± 11.01 171.46 ± 9.09 0.445
F 26.41 ± 4.21 29.07 ± 4.99# 32.91 ± 9.21# 33.46 ± 4.13# < 0.001
BMI; kg ­m−2
M 26.55 ± 3.66 28.36 ± 4.41# 31.28 ± 4.08#& 30.43 ± 4.36# < 0.001
F 29.60 ± 3.82 31.66 ± 4.24# 33.05 ± 7.32 33.25 ± 3.32 0.001
Arm circumference; cm
M 30.83 ± 3.10 32.34 ± 3.49# 33.52 ± 4.23# 33.53 ± 4.20# < 0.001
F 32.93 ± 2.27 33.89 ± 3.30 35.55 ± 3.08# 35.00 ± 3.33 0.003
Neck circumference; cm #
M 37.57 ± 2.84 38.98 ± 2.78 40.28 ± 2.88# 41.15 ± 4.35# < 0.001
F 94.30 ± 9.73 99.46 ± 10.27# 110.88 ± 16.56#& 108.18 ± 9.60# < 0.001
Chest circumference; cm
M 96.83 ± 11.55 100.68 ± 11.14 107.04 ± 8.37# 106.88 ± 10.37# < 0.001
F 87.93 ± 11.06 94.54 ± 12.68# 104.83 ± 17.32# 105.37 ± 11.66# < 0.001
Waist circumference; cm # #&
M 94.32 ± 9.73 99.82 ± 11.81 106.64 ± 9.77 104.23 ± 10.25# < 0.001
F 91.79 ± 10.98 99.01 ± 12.68# 108.27 ± 16.02# 108.37 ± 10.72# < 0.001
Abdomen circumference; cm
M 96.00 ± 9.25 101.15 ± 11.56# 108.52 ± 9.23#& 106.64 ± 10.55# < 0.001
F 101.34 ± 11.28 103.33 ± 12.13 108.11 ± 17.07 104.62 ± 20.85 0.346
Hip circumference; cm
M 101.22 ± 8.25 104.64 ± 8.24# 108.64 ± 8.76# 106.15 ± 8.87 < 0.001
F 15.49 ± 1.15 15.71 ± 1.22 16.71 ± 1.97 16.00 ± 0.70 0.052
Wrist circumference; cm
M 17.44 ± 1.15 17.61 ± 0.97 18.12 ± 1.22 17..36 ± 1.31 0.075
F 18.66 ± 6.34 21.34 ± 8.21 28.86 ± 15.23& 23.96 ± 5.39 0.001
Subscapular skinfold; mm
M 19.10 ± 7.03 19.56 ± 9.10 26.77 ± 10.79#& 22.00 ± 7.69 0.002
F 9.38 ± 3.27 10.88 ± 5.31 14.03 ± 8.77# 9.92 ± 2.94 0.013
Biceps skinfold; mm
M 8.71 ± 3.80 8.60 ± 3.48 8.99 ± 3.76 8.54 ± 3.37 0.979
F 13.23 ± 4.85 13.97 ± 4.62 18.40 ± 13.00 15.44 ± 3.92 0.76
Triceps skinfold; mm
M 10.70 ± 4.38 10.23 ± 3.77 12.95 ± 4.96 10.66 ± 3.16 0.081
F 17.15 ± 5.85 18.88 ± 8.27 23.97 ± 10.18# 19.92 ± 4.05 0.037
Suprailiac skinfold; mm
M 17.32 ± 6.57 17.05 ± 7.44 23.50 ± 11.31#& 15.77 ± 6.70 0.004

Table 3.  A comparison of the anthropometric variables across different stage of the hepatic fibrosis in male
and female participants. BMI body mass index. Data are presented as means ± standard deviations. P values
were obtained from analysis of variance (ANOVA), followed by Tukey’s post hoc test. # Significant difference
(P < 0.05) compared with grade 0; &Significant difference (P < 0.05) compared with grade 1; $Significant
difference (P < 0.05) compared with grade 2.

The proposed algorithm identified in this research can be used by the health systems for several reasons.
Screening of the presence or absence of NAFLD with the help of non-invasive anthropometric measurements
can be achieved with simple and cheap ­equipment57. Moreover, performing the measurement task needs less
specialty knowledge therefore can be implemented in several health centres (e.g., primary practice) and also
remote areas. Once validated, the resulted assistive technology can serve the clinicians in the prevention of liver
diseases. There are limitations of the present research that need to be addressed. A small sample size might have
potentially limited the results of ML prediction. Although, the small sample size was accounted for by multiple
cross-validations, which reduced potential errors. Future studies with larger sample sizes can allocate separate
validation sets and evaluate the model. Moreover, even though the most common method for fatty liver diagnosis,
the ultrasound technique is not the gold standard. Using liver biopsy outcomes would generate more valid results.
Also, to increase the predictive accuracy of the proposed model for NAFLD prediction, future studies should
include other body composition and anthropometric measures such as sagittal abdominal diameter (SAD) and
peri-renal ­fat58.

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Figure 1.  Box plots showing different classification methods applied to the dataset for presence of fatty liver.
Box plots are generated by performing 50 individual runs for each classifier. This will assure that the achieved
results are reliable.

Figure 2.  Box plots showing different classification methods applied to the dataset for stages of steatosis. Box
plots are generated by performing 50 individual runs for each classifier. This will assure that the achieved results
are reliable.

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Figure 3.  Box plots showing different classification methods applied to the dataset for stages of fibrosis. Box
plots are generated by performing 50 individual runs for each classifier. This will assure that the achieved results
are reliable.

Figure 4.  Box plots showing relative feature importance for presence of fatty liver. hx history, cm centimeter, kg
kilograms, BMI body mass index, MUAC​mid-upper arm circumference.

Figure 5.  Box plots showing relative feature importance for stages of steatosis. hx history, cm centimeter, kg
kilograms, BMI body mass index, MUAC​mid-upper arm circumference.

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Figure 6.  Box plots showing relative feature importance for stages of fibrosis. hx history, cm centimeter, kg
kilograms, BMI body mass index, MUAC​mid-upper arm circumference.

Variable Importance value

Gender 0.009424
Age 0.032057
Diabetes history 0.012520
Height 0.024799
Weight 0.047842
BMI (kg/m2) 0.053846
Total fat (%) 0.038906
Fat mass (kg) 0.049188
Muscle mass(kg) 0.029346
Right leg fat (kg) 0.035543
Right leg muscle (kg) 0.029538
Left leg fat (kg) 0.034062
Left leg muscle (kg) 0.030156
Right arm fat (kg) 0.039354
Right arm muscle (kg) 0.031292
Left arm fat (kg) 0.045013
Left arm muscle (kg) 0.031422
Trunk fat (kg) 0.056131
Trunk muscle (kg) 0.030482
Neck circumference (cm) 0.038175
Chest circumference (cm) 0.054649
Waist circumference (cm) 0.061709
Abdominal circumference (cm) 0.061626
Hip circumference (cm) 0.034063
Mid upper arm circumference (cm) 0.041080
Acanthosis nigricans 0.015046
Neck fat 0.016576
Sub-chin fat 0.016157

Table 4.  Variable importance from the random forest method for fatty liver (presence of any stage).

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Variable Importance value

Gender 0.011916
Age 0.033425
Diabetes history 0.018186
Height 0.026744
Weight 0.04809
BMI (kg/m2) 0.050049
Total fat (%) 0.035433
Fat mass (kg) 0.043273
Muscle mass(kg) 0.034973
Right leg fat (kg) 0.034236
Right leg muscle (kg) 0.035191
Left leg fat (kg) 0.033943
Left leg muscle (kg) 0.033304
Right arm fat (kg) 0.038543
Right arm muscle (kg) 0.03686
Left arm fat (kg) 0.037995
Left arm muscle (kg) 0.037145
Trunk fat (kg) 0.051388
Trunk muscle (kg) 0.035925
Neck circumference (cm) 0.039854
Chest circumference (cm) 0.05247
Waist circumference (cm) 0.052178
Abdominal circumference (cm) 0.053468
Hip circumference (cm) 0.03506
Mid upper arm circumference (cm) 0.040977
Acanthosis nigricans 0.015976
Neck fat 0.018529
Sub-chin fat 0.014871

Table 5.  Variable Importance from the random forest method for steatosis stage.

Conclusion
Present findings show that applying a ML classification model on anthropometric and body composition variables
predicted the presence of fatty liver disease. ML-based decision support systems offer potential to assist physicians
with screening, diagnosis and prevention of NAFLD. ML-based decision support systems could be of particular
value for providing services at a population level and remote health care where there is a lack of trained specialists.

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Variable Importance value

Gender 0.013453
Age 0.037938
Diabetes history 0.020626
Height 0.032533
Weight 0.045225
BMI (kg/m2) 0.045191
Total fat (%) 0.038413
Fat mass (kg) 0.039101
Muscle mass(kg) 0.041035
Right leg fat (kg) 0.035216
Right leg muscle (kg) 0.040116
Left leg fat (kg) 0.034831
Left leg muscle (kg) 0.039268
Right arm fat (kg) 0.036479
Right arm muscle (kg) 0.041001
Left arm fat (kg) 0.035263
Left arm muscle (kg) 0.040377
Trunk fat (kg) 0.041605
Trunk muscle (kg) 0.040320
Neck circumference (cm) 0.040930
Chest circumference (cm) 0.043684
Waist circumference (cm) 0.049580
Abdominal circumference (cm) 0.049180
Hip circumference (cm) 0.037576
Mid upper arm circumference (cm) 0.037792
Acanthosis nigricans 0.013215
Neck fat 0.018472
Sub-chin fat 0.011579

Table 6.  Variable importance from the random forest method for fibrosis.

Data availability
The datasets used and/or analyzed in the current study are available from the corresponding author upon
reasonable request.

Received: 13 April 2022; Accepted: 22 March 2023

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Acknowledgements
We are grateful to all participants and assistants of this study.

Author contributions
Study concept and design: F.R. and M.R. Analysis and interpretation of data: H.A., A.S., R.D., G.S. and D.S.
Drafting the manuscript: R.D., M.N., S.M.S.I. Critical revision of the manuscript for important intellectual
content: F.R., R.M., S.M.S.I., R.D. Study supervision: F.R. All authors provided final approval of the version to
be published and agreed to be accountable for all aspects of the work.

Funding
The study was supported by Mashhad University of Medical Sciences, Mashhad, Iran (Code: IR.MUMS.
fm.REC.1395.64). The funder was not involved in the study design, data analysis and interpretation, or
manuscript writing.

Competing interests
The authors declare no competing interests.

Additional information
Supplementary Information The online version contains supplementary material available at https://​doi.​org/​
10.​1038/​s41598-​023-​32129-y.
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