J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://jocmr.elmerjournals.com

Original Article

Volume 18, Number 2, February 2026, pages 83-98

Investigating Factors Influencing Disease Progression in Patients With Non-Alcoholic Fatty Liver Disease

↓ Figure 5. Comparison of the ROC curve between cluster 1 and cluster 2. ROC: receiver operating characteristic.

↓ **Table 1.** Incidence Rates and Hazard Ratios of Clinical Outcomes Between the Four Clusters
Clinical endpoints	Clusters	Number of events	Follow-up^a	Incidence rate^b	Hazard ratio (95% CI)
^aFollow-ups were presented by person-years. ^bIncidence rates were presented by per 10,000 person-years. CI: confidence interval; HCC: hepatocellular carcinoma; LC: liver cirrhosis.
Primary 1	2	53	7,171	73.91	1.000 (Reference)	-
	1	102	2,006	508.47	6.918 (4.963, 9.645)	< 0.0001
	3	53	7,001	75.70	1.027 (0.702, 1.502)	0.8920
	4	14	1,002	139.72	1.896 (1.052, 3.417)	0.0332
Primary 2	2	25	7,171	34.86	1.000 (Reference)	-
	1	28	2,006	139.58	3.964 (2.310, 6.803)	< 0.0001
	3	21	7,001	30.00	0.861 (0.482, 1.539)	0.6143
	4	2	1,002	19.96	0.572 (0.135, 2.414)	0.4467
LC	2	19	7,171	26.50	1.000 (Reference)	-
	1	18	2,006	89.73	3.320 (1.741, 6.331)	0.0003
	3	14	7,001	20.00	0.756 (0.379, 1.507)	0.4262
	4	2	1,002	19.96	0.750 (0.175, 3.219)	0.6987
HCC	2	6	7,210	8.32	1.000 (Reference)	-
	1	12	2,024	59.29	7.097 (2.661, 18.928)	< 0.0001
	3	8	7,032	11.38	1.370 (0.475, 3.950)	0.5596
	4	1	1,00	9.97	1.200 (0.145, 9.972)	0.8657
All-cause mortality	2	32	7,219	44.33	1.000 (Reference)	-
	1	85	2,049	414.84	9.554 (6.360, 14.350)	< 0.0001
	3	33	7,052	46.80	1.056 (0.650, 1.718)	0.8249
	4	13	1,005	129.35	2.934 (1.540, 5.589)	0.0011
Liver-associated mortality	2	2	7,219	2.77	1.000 (Reference)	-
	1	4	2,049	19.52	7.459 (1.364, 40.786)	0.0204
	3	0	7,052	0.00	NA	NA
	4	0	1,005	0.00	NA	NA

↓ Table 1. Incidence Rates and Hazard Ratios of Clinical Outcomes Between the Four Clusters

Clinical endpoints

Clusters

Number of events

Follow-up^a

Incidence rate^b

Hazard ratio (95% CI)

Crude

P-value

^aFollow-ups were presented by person-years. ^bIncidence rates were presented by per 10,000 person-years. CI: confidence interval; HCC: hepatocellular carcinoma; LC: liver cirrhosis.

Primary 1

7,171

73.91

1.000 (Reference)

102

2,006

508.47

6.918 (4.963, 9.645)

< 0.0001

7,001

75.70

1.027 (0.702, 1.502)

0.8920

1,002

139.72

1.896 (1.052, 3.417)

0.0332

Primary 2

7,171

34.86

1.000 (Reference)

2,006

139.58

3.964 (2.310, 6.803)

< 0.0001

7,001

30.00

0.861 (0.482, 1.539)

0.6143

1,002

19.96

0.572 (0.135, 2.414)

0.4467

7,171

26.50

1.000 (Reference)

2,006

89.73

3.320 (1.741, 6.331)

0.0003

7,001

20.00

0.756 (0.379, 1.507)

0.4262

1,002

19.96

0.750 (0.175, 3.219)

0.6987

HCC

7,210

8.32

1.000 (Reference)

2,024

59.29

7.097 (2.661, 18.928)

< 0.0001

7,032

11.38

1.370 (0.475, 3.950)

0.5596

1,00

9.97

1.200 (0.145, 9.972)

0.8657

All-cause mortality

7,219

44.33

1.000 (Reference)

2,049

414.84

9.554 (6.360, 14.350)

< 0.0001

7,052

46.80

1.056 (0.650, 1.718)

0.8249

1,005

129.35

2.934 (1.540, 5.589)

0.0011

Liver-associated mortality

7,219

2.77

1.000 (Reference)

2,049

19.52

7.459 (1.364, 40.786)

0.0204

7,052

0.00

1,005

0.00

↓ **Table 2.** Cluster 1 Compared With Cluster 2 (17 Variables of the Full Model)
Full model	Cluster 1 (n = 658)	Cluster 2 (n = 2,048)	Variables type	Odds ratio, 95% CI	P-value	Estimate (β)
Odds ratios for continuous variables are presented using clinically meaningful increments (e.g., per 10 units) to enhance clinical interpretability (except for hemoglobin (g/dL), for which a one-unit increment may be clinically substantial). BUN: blood urea nitrogen; CI: confidence interval; CRP: C-reactive protein; eGFR: estimated glomerular filtration rate; Hgb: hemoglobin; LDL-C: low-density lipoprotein cholesterol; PTTp: partial thromboplastin time, plasma; RDW-SD: red cell distribution width-standard deviation.
Intercept						12.3011
Age (years)	67.9 (59.70, 75.90)	55.3 (43.65, 63.9)	Explanatory	1.77 (1.51, 2.10)	< 0.0001	0.0576
Chronic kidney disease	137 (20.82)	39 (1.90)	Explanatory	4.521 (2.028, 10.074)	0.0002	1.5086
Other urinary system disease	172 (26.14)	49 (2.39)	Explanatory/exploratory	6.894 (3.285, 14.470)	< 0.0001	1.9307
Sodium chloride	473 (71.88)	378 (18.46)	Unknown/exploratory	10.497 (6.750, 16.325)	< 0.0001	2.3511
Metformin	228 (34.65)	307 (14.99)	Explanatory	3.877 (2.382, 6.311)	< 0.0001	1.3551
PTTp (s)	27.75 (26.56, 29.58)	27.62 (26.87, 28.70)	Explanatory/exploratory	7.31 (3.98, 13.35)	< 0.0001	0.1988
LDL-C (mg/dL)	92.95 (71.00, 111.20)	108.86 (92.45, 125.45)	Explanatory/exploratory	0.75 (0.69, 0.82)	< 0.0001	−0.0282
pCO₂ (mm Hg)	40.98 (38.00, 43.80)	42.24 (39.86, 44.44)	Explanatory/exploratory	0.23 (0.15, 0.36)	< 0.0001	−0.1475
Glucose level (mg/dL)	123 (104, 159)	109 (101, 124)	Explanatory/exploratory	1.23 (1.16, 1.29)	< 0.0001	0.0203
CRP (mg/L)	11.06 (3.18, 33.27)	8.81 (3.59, 19.56)	Explanatory	1.16 (1.08, 1.26)	< 0.0001	0.0152
Total protein (mg/dL)	17.8 (10.68, 34.56)	16.42 (10.6, 30.2)	Explanatory/exploratory	1.04 (1.01, 1.06)	0.0026	0.00358
Lymphocyte (%)	21.83 (14.60, 27.20)	27.34 (23.44, 30.96)	Explanatory/exploratory	0.21 (0.15, 0.29)	< 0.0001	−0.1564
Hgb (g/dL)	12.20 (11.00, 13.10)	14.23 (13.50, 15.10)	Explanatory/exploratory	0.175 (0.140, 0.220)	< 0.0001	−1.7410
RDW-SD (fL)	43.40 (41.80, 45.60)	42.25 (41.00, 43.52)	Explanatory/exploratory	9.91 (4.66, 21.1)	< 0.0001	0.2298
BUN (mg/dL)	17.10 (13.00, 24.30)	14.11 (12.22, 16.40)	Explanatory/exploratory	2.79 (1.98, 3.87)	< 0.0001	0.1023
eGFR (mL/min/1.73 m²)	70.20 (48.80, 88.90)	90.75 (77.30, 104.70)	Explanatory/exploratory	0.78 (0.73, 0.85)	< 0.0001	−0.0238
Urine creatinine (mg/dL)	108.68 (79.44, 143.70)	126.28 (101.08, 151.46)	Explanatory/exploratory	0.90 (0.86, 0.95)	< 0.0001	−0.0100

↓ Table 2. Cluster 1 Compared With Cluster 2 (17 Variables of the Full Model)

Full model

Cluster 1 (n = 658)

Cluster 2 (n = 2,048)

Variables type

Odds ratio, 95% CI

P-value

Estimate (β)

Odds ratios for continuous variables are presented using clinically meaningful increments (e.g., per 10 units) to enhance clinical interpretability (except for hemoglobin (g/dL), for which a one-unit increment may be clinically substantial). BUN: blood urea nitrogen; CI: confidence interval; CRP: C-reactive protein; eGFR: estimated glomerular filtration rate; Hgb: hemoglobin; LDL-C: low-density lipoprotein cholesterol; PTTp: partial thromboplastin time, plasma; RDW-SD: red cell distribution width-standard deviation.

Intercept

12.3011

Age (years)

67.9 (59.70, 75.90)

55.3 (43.65, 63.9)

Explanatory

1.77 (1.51, 2.10)

< 0.0001

0.0576

Chronic kidney disease

137 (20.82)

39 (1.90)

Explanatory

4.521 (2.028, 10.074)

0.0002

1.5086

Other urinary system disease

172 (26.14)

49 (2.39)

Explanatory/exploratory

6.894 (3.285, 14.470)

< 0.0001

1.9307

Sodium chloride

473 (71.88)

378 (18.46)

Unknown/exploratory

10.497 (6.750, 16.325)

< 0.0001

2.3511

Metformin

228 (34.65)

307 (14.99)

Explanatory

3.877 (2.382, 6.311)

< 0.0001

1.3551

PTTp (s)

27.75 (26.56, 29.58)

27.62 (26.87, 28.70)

Explanatory/exploratory

7.31 (3.98, 13.35)

< 0.0001

0.1988

LDL-C (mg/dL)

92.95 (71.00, 111.20)

108.86 (92.45, 125.45)

Explanatory/exploratory

0.75 (0.69, 0.82)

< 0.0001

−0.0282

pCO₂ (mm Hg)

40.98 (38.00, 43.80)

42.24 (39.86, 44.44)

Explanatory/exploratory

0.23 (0.15, 0.36)

< 0.0001

−0.1475

Glucose level (mg/dL)

123 (104, 159)

109 (101, 124)

Explanatory/exploratory

1.23 (1.16, 1.29)

< 0.0001

0.0203

CRP (mg/L)

11.06 (3.18, 33.27)

8.81 (3.59, 19.56)

Explanatory

1.16 (1.08, 1.26)

< 0.0001

0.0152

Total protein (mg/dL)

17.8 (10.68, 34.56)

16.42 (10.6, 30.2)

Explanatory/exploratory

1.04 (1.01, 1.06)

0.0026

0.00358

Lymphocyte (%)

21.83 (14.60, 27.20)

27.34 (23.44, 30.96)

Explanatory/exploratory

0.21 (0.15, 0.29)

< 0.0001

−0.1564

Hgb (g/dL)

12.20 (11.00, 13.10)

14.23 (13.50, 15.10)

Explanatory/exploratory

0.175 (0.140, 0.220)

< 0.0001

−1.7410

RDW-SD (fL)

43.40 (41.80, 45.60)

42.25 (41.00, 43.52)

Explanatory/exploratory

9.91 (4.66, 21.1)

< 0.0001

0.2298

BUN (mg/dL)

17.10 (13.00, 24.30)

14.11 (12.22, 16.40)

Explanatory/exploratory

2.79 (1.98, 3.87)

< 0.0001

0.1023

eGFR (mL/min/1.73 m²)

70.20 (48.80, 88.90)

90.75 (77.30, 104.70)

Explanatory/exploratory

0.78 (0.73, 0.85)

< 0.0001

−0.0238

Urine creatinine (mg/dL)

108.68 (79.44, 143.70)

126.28 (101.08, 151.46)

Explanatory/exploratory

0.90 (0.86, 0.95)

< 0.0001

−0.0100

↓ **Table 3.** The First Sensitivity Analysis Cluster 1 Compared With Cluster 2 (17 Variables of Full Model)
Variables	Variables type	Odds ratio, 95% CI	P-value	Estimate (β)
Odds ratios for continuous variables are presented using clinically meaningful increments (e.g., per 10 units) to enhance clinical interpretability (except for hemoglobin (g/dL), for which a one-unit increment may be clinically substantial). BUN: blood urea nitrogen; CKD: chronic kidney disease; CRP: C-reactive protein; eGFR: estimated glomerular filtration rate; Hgb: hemoglobin; LDL-C: low-density lipoprotein cholesterol; PTTp: partial thromboplastin time, plasma; RDW-SD: red cell distribution width-standard deviation.
Intercept				15.8739
Age (years)	Explanatory	1.77 (1.51, 2.10)	< 0.0001	0.0576
CKD	Explanatory	4.521 (2.028, 10.074)	0.0002	0.7543
Other urinary system disease	Explanatory/exploratory	6.894 (3.285, 14.470)	< 0.0001	0.9653
Sodium chloride	Unknown/exploratory	10.497 (6.750, 16.325)	< 0.0001	1.1756
Metformin	Explanatory	3.877 (2.382, 6.311)	< 0.0001	0.6776
PTTp (s)	Explanatory/exploratory	7.31 (3.98, 13.35)	< 0.0001	0.1988
LDL-C (mg/dL)	Explanatory/exploratory	0.75 (0.69, 0.82)	< 0.0001	−0.0282
pCO₂ (mm Hg)	Explanatory/exploratory	0.23 (0.15, 0.36)	< 0.0001	−0.1475
Glucose level (mg/dL)	Explanatory/exploratory	1.23 (1.16, 1.29)	< 0.0001	0.0203
CRP (mg/L)	Explanatory	1.16 (1.08, 1.26)	< 0.0001	0.0152
Total protein (mg/dL)	Explanatory/exploratory	1.04 (1.01, 1.06)	0.0026	0.00358
Lymphocyte (%)	Explanatory/exploratory	0.21 (0.15, 0.29)	< 0.0001	−0.1564
Hgb (g/dL)	Explanatory/exploratory	0.175 (0.140, 0.220)	< 0.0001	−1.7410
RDW-SD (fL)	Explanatory/exploratory	9.91 (4.66, 21.1)	< 0.0001	0.2298
BUN (mg/dL)	Explanatory/exploratory	2.79 (1.98, 3.87)	< 0.0001	0.1023
eGFR (mL/min/1.73 m²)	Explanatory/exploratory	0.78 (0.73, 0.85)	< 0.0001	−0.0238
Urine creatinine (mg/dL)	Explanatory/exploratory	0.90 (0.86, 0.95)	< 0.0001	−0.0100

↓ Table 3. The First Sensitivity Analysis Cluster 1 Compared With Cluster 2 (17 Variables of Full Model)

Variables

Variables type

Odds ratio, 95% CI

P-value

Estimate (β)

Odds ratios for continuous variables are presented using clinically meaningful increments (e.g., per 10 units) to enhance clinical interpretability (except for hemoglobin (g/dL), for which a one-unit increment may be clinically substantial). BUN: blood urea nitrogen; CKD: chronic kidney disease; CRP: C-reactive protein; eGFR: estimated glomerular filtration rate; Hgb: hemoglobin; LDL-C: low-density lipoprotein cholesterol; PTTp: partial thromboplastin time, plasma; RDW-SD: red cell distribution width-standard deviation.

Intercept

15.8739

Age (years)

Explanatory

1.77 (1.51, 2.10)

< 0.0001

0.0576

CKD

Explanatory

4.521 (2.028, 10.074)

0.0002

0.7543

Other urinary system disease

Explanatory/exploratory

6.894 (3.285, 14.470)

< 0.0001

0.9653

Sodium chloride

Unknown/exploratory

10.497 (6.750, 16.325)

< 0.0001

1.1756

Metformin

Explanatory

3.877 (2.382, 6.311)

< 0.0001

0.6776

PTTp (s)

Explanatory/exploratory

7.31 (3.98, 13.35)

< 0.0001

0.1988

LDL-C (mg/dL)

Explanatory/exploratory

0.75 (0.69, 0.82)

< 0.0001

−0.0282

pCO₂ (mm Hg)

Explanatory/exploratory

0.23 (0.15, 0.36)

< 0.0001

−0.1475

Glucose level (mg/dL)

Explanatory/exploratory

1.23 (1.16, 1.29)

< 0.0001

0.0203

CRP (mg/L)

Explanatory

1.16 (1.08, 1.26)

< 0.0001

0.0152

Total protein (mg/dL)

Explanatory/exploratory

1.04 (1.01, 1.06)

0.0026

0.00358

Lymphocyte (%)

Explanatory/exploratory

0.21 (0.15, 0.29)

< 0.0001

−0.1564

Hgb (g/dL)

Explanatory/exploratory

0.175 (0.140, 0.220)

< 0.0001

−1.7410

RDW-SD (fL)

Explanatory/exploratory

9.91 (4.66, 21.1)

< 0.0001

0.2298

BUN (mg/dL)

Explanatory/exploratory

2.79 (1.98, 3.87)

< 0.0001

0.1023

eGFR (mL/min/1.73 m²)

Explanatory/exploratory

0.78 (0.73, 0.85)

< 0.0001

−0.0238

Urine creatinine (mg/dL)

Explanatory/exploratory

0.90 (0.86, 0.95)

< 0.0001

−0.0100

↓ **Table 4.** The Category of the Clusters in the Secondary Sensitivity Analysis
New clusters (seven clusters)	Old clusters (five clusters)
0	11	0	0	0	0	11
	0.18	0	0	0	0	0.18
	100	0	0	0	0
	100	0	0	0	0
1	0	16	1,846	139	13	2,014
	0	0.27	30.93	2.33	0.22	33.74
	0	0.79	91.66	6.9	0.65
	0	2.04	73.99	5.97	3.71
2	0	0	0	0	315	315
	0	0	0	0	5.28	5.28
	0	0	0	0	100
	0	0	0	0	90
3	0	71	1	3	1	76
	0	1.19	0.02	0.05	0.02	1.27
	0	93.42	1.32	3.95	1.32
	0	9.03	0.04	0.13	0.29
4	0	505	173	193	8	879
	0	8.46	2.9	3.23	0.13	14.73
	0	57.45	19.68	21.96	0.91
	0	64.25	6.93	8.29	2.29
5	0	176	412	883	7	1,478
	0	2.95	6.9	14.79	0.12	24.76
	0	11.91	27.88	59.74	0.47
	0	22.39	16.51	37.95	2
6	0	18	63	1109	6	1,196
	0	0.3	1.06	18.58	0.1	20.04
	0	1.51	5.27	92.73	0.5
	0	2.29	2.53	47.66	1.71
Total	11	786	2495	2327	350	5,969
	0.18	13.17	41.8	38.98	5.86	100

↓ Table 4. The Category of the Clusters in the Secondary Sensitivity Analysis

New clusters (seven clusters)

Old clusters (five clusters)

Total

0.18

100

1,846

139

2,014

0.27

30.93

2.33

0.22

33.74

0.79

91.66

6.9

0.65

2.04

73.99

5.97

3.71

315

5.28

100

1.19

0.02

0.05

0.02

1.27

93.42

1.32

3.95

1.32

9.03

0.04

0.13

0.29

505

173

193

879

8.46

2.9

3.23

0.13

14.73

57.45

19.68

21.96

0.91

64.25

6.93

8.29

2.29

176

412

883

1,478

2.95

6.9

14.79

0.12

24.76

11.91

27.88

59.74

0.47

22.39

16.51

37.95

1109

1,196

0.3

1.06

18.58

0.1

20.04

1.51

5.27

92.73

0.5

2.29

2.53

47.66

1.71

Total

786

2495

2327

350

5,969

0.18

13.17

41.8

38.98

5.86

100