Cumulative effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease in China

Table 3 Risks of new-onset metabolic dysfunction-associated fatty liver disease stratified by different categories of cumulative effects of excess high-normal alanine aminotransferase level

Categories	Univariate, HR (95%CI)	P value	Sex-, WC-, SBP-, DBP- and BMI-adjusted1, HR (95%CI)	P value	Multivariate-adjusted2	P value
Cumulative occurrences of ehALT (n = 3553)
0 (101/1738)	1.000		1.000		1.000
1 (82/851)	1.672 (1.249-2.237)	0.001	1.312 (0.975-1.765)	0.073	1.261 (0.935-1.699)	0.128
2 (70/512)	2.325 (1.714-3.154)	< 0.001	1.495 (1.091-2.049)	0.012	1.443 (1.050-1.982)	0.024
3 (83/452)	2.963 (2.215-3.962)	< 0.001	1.559 (1.142-2.128)	0.005	1.551 (1.135-2.119)	0.006
P value for trend3	< 0.001		0.005		0.005
Equally weighted cumulative effects of ehALT (n = 3553)
Increase per SD4	1.227 (1.149-1.310)	< 0.001	1.090 (1.006-1.182)	0.036	1.088 (1.003-1.179)	0.041
0 (reference)	1.000		1.000		1.000
Q1 (0.01-3.00 U/L)	1.541 (1.069-2.225)	0.020	1.139 (0.785-1.652)	0.493	1.083 (0.744-1.575)	0.678
Q2 (3.01-8.50 U/L)	1.770 (1.261-2.485)	0.001	1.329 (0.941-1.876)	0.106	1.297 (0.916-1.837)	0.916
Q3 (8.51-20.50 U/L)	2.620 (1.926-3.564)	< 0.001	1.671 (1.214-2.300)	0.002	1.651 (1.199-2.273)	0.002
Q4 (≥ 20.51 U/L)	2.852 (2.120-3.838)	< 0.001	1.578 (1.151-2.162)	0.005	1.535 (1.119-2.106)	0.008
P value for trend3	< 0.001		0.005		0.007
Unequally weighted cumulative effects of ehALT (n = 3553)
Increase per SD4	1.231 (1.154-1.312)	< 0.001	1.102 (1.020-1.191)	0.014	1.098 (1.017-1.185)	0.016
0 (reference)	1.000		1.000		1.000
Q1 (0.01-5.00 U/L)	1.709 (1.209-2.416)	0.002	1.190 (0.835-1.697)	0.336	1.114 (0.779-1.591)	0.555
Q2 (5.01-15.00 U/L)	1.749 (1.234-2.478)	0.002	1.283 (0.900-1.830)	0.168	1.278 (0.895-1.826)	0.177
Q3 (15.01-40.50 U/L)	2.319 (1.688-3.187)	< 0.001	1.636 (1.178-2.273)	0.003	1.616 (1.162-2.246)	0.004
Q4 (≥ 40.51 U/L)	2.996 (2.236-4.015)	< 0.001	1.626 (1.191-2.220)	0.002	1.580 (1.155-2.162)	0.004
P value for trend3	< 0.001		0.003		0.004
Single ehALT occurrence (control group, n = 1969)
Increase per SD4	1.055 (0.866-1.286)	0.594	1.010 (0.819-1.245)	0.929	1.012 (0.811-1.262)	0.917
0 (reference)	1.000		1.000		1.000
Q1 (0.01-1.50 U/L)	0.688 (0.218-2.171)	0.524	0.497 (0.150-1.528)	0.214	0.557 (0.174-1.783)	0.324
Q2 (1.51-3.50 U/L)	0.612 (0.151-2.485)	0.492	0.462 (0.113-1.886)	0.282	0.352 (0.085-1.462)	0.151
Q3 (3.51-8.50 U/L)	1.250 (0.460-3.397)	0.662	1.326 (0.486-3.620)	0.582	1.043 (0.374-2.908)	0.936
Q4 (≥ 8.51 U/L)	1.990 (0.808-4.898)	0.134	1.688 (0.675-4.221)	0.263	1.828 (0.772-4.593)	0.199
P value for trend3	0.142		0.259		0.264

¹Adjusted for sex, waist circumference, systolic blood pressure, diastolic blood pressure, and body mass index.

²Adjusted for sex, waist circumference, systolic blood pressure, diastolic blood pressure, body mass index, serum uric acid, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, and glycated haemoglobin.

³For the trend test, Cox proportional hazards regression models were used with group medians in each group instead of grouping variables (e.g., 0, Q₁, Q₂, Q₃, and Q₄). The cumulative excess high-normal alanine aminotransferase (ehALT) level concentrations were 12 U/L, 15 U/L, 20 U/L, and 26 U/L in the four groups, and the equally weighted cumulative effects of ehALT were 0, 1.5 U/L, 5.5 U/L, 13 U/L, and 33.5 U/L in the five groups. The unequally weighted cumulative effects of ehALT were 0, 2.5 U/L, 10.5 U/L, 24.5 U/L, and 69 U/L in the five groups, and the single ehALT occurrence (control group) were 0, 0.5 U/L, 2.5 U/L, 5.5 U/L, and 17.5 U/L in the five groups.

⁴The SD of the equally weighted cumulative effects of excess high-normal alanine aminotransferase (ehALT) level was 15.93, the SD of the unequally weighted cumulative effects of ehALT was 32.73, and the SD of a single ehALT occurrence (control group, only 2019 ALT > 18.5 U/L) was 3.76.

WC: Waist circumference; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; BMI: Body mass index; ehALT: Excess high-normal alanine aminotransferase; HR: Hazard ratio; CI: Confidence interval.