LASSO-derived model for the prediction of lean-non-alcoholic fatty liver disease in examinees attending a routine health check-up

Figures & data

Figure 1. Flow chart of the study. BMI: body mass index

Figure 2. This heatmap visually represents the correlation matrix of 23 features, including age, sex, BMI, WC, BW, body fat, WHR, history of hypertension (HTN) and diabetes mellitus (DM), fasting glucose, exercise frequency, alcohol drinking frequency, platelet count, alkaline phosphatase, HbA1c, cholesterol, HDL-C, LDL-C, triglyceride levels, uric acid, muscle mass, visceral fat, and total cholesterol/HDL-C ratio. The color spectrum in the heatmap spans from deep blue, denoting positive correlations, to deep red, indicating negative correlations.

Table 1. Clinical characteristics of the training and validation sets.

	Training cohort (n = 1162)	Validation cohort (n = 1163)	p-value
Age (year)	48.32 ± 12.33	47.83 ± 12.50	.343
Sex (%)			.742
female	740 (63.7%)	733 (63%)
male	422 (36.3%)	430 (37%)
BMI (kg/m2)	21.22 ± 1.85	21.21 ± 1.91	.903
WC (cm)	78.04 ± 7.00.	77.59 ± 7.10	.125
BW (kg)	57.76 ± 8.45	58.00 ± 8.50	.487
Body fat (%)	21.64 ± 5.26	21.52 ± 5.38	.598
Waist and hip ratio (%)	0.80 ± 0.08	0.800 ± 0.08	.915
Hypertension (%)	139 (12%)	107 (9.2%)	.030*
Diabetes (%)	66 (5.7%)	54 (4.6%)	.259
Exercise frequency			.932
≥ 5 times/ week	137 (11.8%)	143 (12.3%)
3–5 times/week	288 (24.8%)	286 (24.6%)
<3 times/week	737 (63.4%)	734 (63.1%)
Alcohol drinking frequency			.785
≥ 3 times/ week	60 (5.2%)	63 (5.4%)
<3 times/week	1102 (94.8%)	1100 (94.6%)
Fasting glucose (mg/dL)	91.14 ± 18.77	89.97 ± 19.42	.137
HbA1c (%)	5.77 ± 0.67	5.73 ± 0.72	.138
Cholesterol (mg/dL)	198.86 ± 37.48	197.22 ± 37.89	.293
HDL (mg/dL)	57.06 ± 14.24	57.44 ± 14.26	.525
LDL (mg/dL)	121.94 ± 33.34	120.56 ± 33.33	.318
Total Cholesterol/HDL (%)	3.66 ± 1.04	3.62 ± 1.06	.271
Triglyceride (mg/dL)	101.44 ± 70.42	98.41 ± 66.07	.285
Alkaline Phosphatase (U/L)	62.59 ± 22.51	60.70 ± 18.78	.032*
Platelet Count (K/uL)	248.94 ± 61.47	246.00 ± 57.79	.235
Muscle mass (kg)	42.00 ± 7.19	42.23 ± 7.24	.434
Visceral fat (kg)	1.34 ± 0.52	1.34 ± 0.53	.874
Fatty liver (%)	154 (13.3%)	147 (12.6%)	.660

Abbreviation: BMI: Body Mass Index; WC: Waist circumference; BW: Body weight; HbA1c: hemoglobin A1c; HDL-C: high density lipoprotein-cholesterol; LDL-C: low density lipoprotein-cholesterol.

Table 2. Demographic data comparison based on non-alcoholic fatty liver status, stratified from training set.

		no fatty liver (n = 1008)	fatty liver (n = 154)	p-value
Age(year)		47.68 ± 12.46	52.51 ± 10.58	<.005
Sex (%)	female	680 (67%)	60 (39%)	<.005
	male	328 (33%)	94 (61%)
BMI (kg/m^2)		21.04 ± 1.87	22.41 ± 1.18	<.005
WC (cm)		77.31 ± 6.92	82.79 ± 5.49	<.005
body weight (kg)		56.99 ± 8.27	62.81 ± 7.95	<.005
Body fat (%)		21.45 ± 5.33	22.86 ± 4.61	.032
Waist hip ratio		0.79 ± 0.08	0.86 ± 0.07	<.005
Hypertension	(%)	103 (10%)	36 (23%)	<.005
Diabetes mellitus	(%)	48 (5%)	18 (12%)	.001
Exercise frequency	≥ 5 times/ week	118 (12%)	19 (12%)	.957
	3–5 times/week	251 (25%)	37 (24%)
	<3 times/week	639 (63%)	98 (64%)
Alcohol drinking frequency	≥ 3 times/ week	53 (5%)	7 (5%)	.710
	<3 times/week	955 (95%)	147 (95%)
Fasting glucose (mg/dL)		90.19 ± 18.17	97.39 ± 21.31	<.005
HbA1c (%)		5.73 ± 0.65	6.05 ± 0.73	< .005
Cholesterol (mg/dL)		198.95 ± 37.55	198.29 ± 37.16	.837
HDL-C (mg/dL)		58.67 ± 14.13	46.55 ± 9.81	<.005
LDL-C (mg/dL)		121.54 ± 33.40	124.62 ± 32.92	.286
Total Cholesterol/HDL-C (%)		3.55 ± 1.00	4.40 ± 1.05	<.005
Triglyceride (mg/dL)		92.23 ± 57.98	161.73 ± 106.24	<.005
Alkaline Phosphatase (U/L)		61.65 ± 22.96	68.67 ± 18.23	<.005
Platelet Count (K/uL)		247.48 ± 60.94	258.53 ± 64.25	.038
Muscle mass (kg)		41.53 ± 7.00	45.08 ± 7.64	<.005
Visceral fat (kg)		1.28 ± 0.51	1.73 ± 0.44	<.005

BMI: Body Mass Index; WC: Waist circumference; BW: Body weight; HbA1c: hemoglobin A1c; HDL-C: high density lipoprotein-cholesterol; LDL-C: low density lipoprotein-cholesterol.

Table 3. Univariable and LASSO-derived multivariable logistic regression for predicting fatty liver in subjects with lean BMI.

	OR	CI	p-value
Univariate analysis
Age (year)	1.035	1.025–1.045	<.001
Sex^a (%)	2.808	2.193–3.595	<.001
BMI (kg/m2)	1.768	1.606–1.946	<.001
WC (cm)	1.135	1.112–1.159	<.001
BW (kg)	1.078	1.063–1.094	<.001
Body fat (%)	1.063	1.038–1.089	<.001
Waist and hip ratio (%)	67023.428	12074.297–372041.533	<.001
Hypertension (%)	2.877	2.104–3.935	<.001
Diabetes (%)	4.046	2.720–6.017	<.001
Fasting glucose (mg/dL)	1.019	1.014–1.025	<.001
Exercise frequency	1.055	0.885–1.258	.548
Alcohol drinking frequency	0.860	0.514–1.440	.567
Platelet Count (K/uL)	1.003	1.001–1.005	.004
Alkaline Phosphatase (U/L)	1.017	1.010–1.023	<.001
HbA1c (%)	1.919	1.611–2.287	<.001
Cholesterol (mg/dL)	1.002	0.999–1.005	.295
HDL-C (mg/dL)	0.920	0.909–0.932	<.001
LDL-C (mg/dL)	1.005	1.002–1.009	.003
Triglyceride (mg/dL)	1.013	1.012–1.015	<.001
Uric Acid (mg/dL)	1.699	1.557–1.854	<.001
Muscle mass (kg)	1.058	1.041–1.075	<.001
Visceral fat (kg)	5.393	4.149–7.009	<.001
Total Cholesterol/HDL-C (%)	2.150	1.918–2.411	<.001
LASSO-derived model
Prediction model	675.876	230.373–1982.906	<.001

Abbreviation: BMI: Body Mass Index; WC: Waist circumference; BW: Body weight; HbA1c: hemoglobin A1c; HDL-C: high density lipoprotein-cholesterol; LDL-C: low density lipoprotein-cholesterol.

^a Female sex: reference.

Figure 3. Nomogram for lean nonalcoholic fatty liver disease prediction.

Table 4. Prediction performance of LASSO and FLI models, n = 1163.

Model	Cut point	Sensitivity	95% CI	Specificity	95% CI	+LR	95% CI	−LR	95% CI	+PV	95% CI	−PV	95% CI
LASSO	>0.1484	75.69	67.9–82.4	79.86	77.3–82.3	3.76	3.4–4.1	0.3	0.2–0.4	34.8	29.6–40.4	95.9	94.3–97.1
FLI	>15.45	76.19	68.5–82.8	78.35	75.7–80.8	3.52	3.2–3.9	0.3	0.2–0.4	33.7	28.7–39.1	95.8	94.2–97.0

LASSO: least absolute shrinkage, and selection operator; AIC: Akaike information criterion; BIC: Bayesian information criterion; AUC: area under the ROC curve; CI: confidence interval; LR: likelihood ratio; PV: predictive value.

Table 5. Prediction performance and comparison of LASSO and FLI models.

Model	AIC	BIC	AUC	95% CI	p-value*
LASSO	709.610	734.870	0.8416	0.811–0.872	.470
FLI	755.360	765.476	0.8322	0.801–0.863

LASSO: least absolute shrinkage and selection operator; AIC: Akaike information criterion; BIC: Bayesian information criterion; AUC: area under the ROC curve; CI: confidence interval.

* LASSO vs. FLI model.

Data availability statement

The study questionnaires and raw data are available from the project PI via email: [email protected]