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

doi:10.3748/wjg.v30.i10.1346

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Cohort Study

World J Gastroenterol. Mar 14, 2024; 30(10): 1346-1357
Published online Mar 14, 2024. doi: 10.3748/wjg.v30.i10.1346

Table 1 Definitions of some specific terms

Term	Definition
lALT group	ALT ≤ optimal ALT cut-off points (U/L)
hALT group	Optimal ALT cut-off point < ALT ≤ 40 (U/L)
aALT group	ALT > 40 (U/L)
ehALT	ALT-optimal ALT cut-off point, if ehALT < 0, redefine ehALT = 0
Cumulative occurrences of ehALT	Sum of times that ehALT > 0 in 2017-2019, time = {0, 1, 2, 3}
Equally weighted cumulative effects of ehALT	Sum of ehALT levels with a weight of 1 in 2017-2019, i.e., ehALT₂₀₁₇ + ehALT₂₀₁₈ + ehALT₂₀₁₉
Unequally weighted cumulative effects of ehALT	Sum of ehALT levels with an increasing weight in 2017-2019, i.e., 1 × ehALT₂₀₁₇ + 2 × ehALT₂₀₁₈ + 3 × ehALT₂₀₁₉
Single ehALT occurrence	ehALT₂₀₁₉ along with ehALT₂₀₁₇ = 0 and ehALT₂₀₁₈ = 0

ALT: Alanine aminotransferase; lALT: Low-normal alanine aminotransferase; hALT: High-normal alanine aminotransferase; aALT: Abnormal alanine aminotransferase; ehALT: Excess high-normal alanine aminotransferase.

Table 2 Baseline characteristics of 3553 participants on follow-up

Variables	Total (3553)	lALT group (2409)	hALT group (1046)	aALT group (98)	F/χ²^/H	P value
Sex, n (%)					264.16	< 0.001
Male	1741 (49.00)	955 (39.64)	712 (68.07)	74 (75.51)
Female	1812 (51.00)	1454 (60.36)	334 (31.93)^a	24 (24.49)^a
Age (yr), mean (SD)	48.39 (15.13)	47.82 (15.39)	50.17 (14.54)^a	43.51 (12.59)^a^,^b	14.11	< 0.001
WC (cm), mean (SD)	85.81 (1.81)	85.79 (1.67)	85.85 (1.94)	85.85 (3.11)	0.44	0.643
SBP (mmHg), mean (SD)	120.33 (16.66)	119.18 (16.64)	122.93 (16.70)^a	121.08 (13.41)	18.77	< 0.001
DBP (mmHg), mean (SD)	72.68 (10.27)	71.70 (10.03)	74.81 (10.60)^a	74.07 (8.92)^a	35.09	< 0.001
BMI (kg/m²), mean (SD)	22.80 (2.41)	22.46 (2.39)	23.46 (2.32)^a	23.94 (2.21)^a	76.76	< 0.001
SUA (μmol/L), mean (SD)	290.53 (72.07)	280.17 (69.87)	311.33 (71.51)^a	323.01 (74.16)^a	82.00	< 0.001
TC (mmol/L), mean (SD)	4.53 (0.84)	4.51 (0.82)	4.58 (0.88)^a	4.55 (0.84)	2.72	0.066
TG (mmol/L), median (IQR)	0.97 (0.72, 1.29)	0.93 (0.70, 1.26)	1.06 (0.79, 1.40)^a	1.09 (0.82, 1.52)^a	79.73	< 0.001
HDL-C (mmol/L), mean (SD)	1.47 (0.34)	1.50 (0.34)	1.42 (0.34)^a	1.39 (0.39)^a	18.51	< 0.001
LDL-C (mmol/L), mean (SD)	2.77 (0.75)	2.74 (0.73)	2.85 (0.78)^a	2.83 (0.72)	7.76	< 0.001
FPG (mmol/L), median (IQR)	4.96 (4.68, 5.25)	4.95 (4.67, 5.21)	5.00 (4.71, 5.30)^a	4.94 (4.65, 5.27)^b	10.65	0.005
HbA1c (%), median (IQR)	5.70 (5.50, 5.70)	5.70 (5.50, 5.70)	5.70 (5.40, 5.70)	5.70 (5.40, 5.70)^a^,^b	10.69	0.005

^aP < 0.05, compared with the low-normal alanine aminotransferase level group.

^bP < 0.05, compared with the high-normal alanine aminotransferase level group.

lALT: Low-normal alanine aminotransferase; hALT: High-normal alanine aminotransferase; aALT: Abnormal alanine aminotransferase; WC: Waist circumference; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; BMI: Body mass index; TC: Total cholesterol; FPG: Fasting plasma glucose; HbA1c: Glycated haemoglobin; TG: Triglycerides; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; SUA: Serum uric acid; IQR: Interquartile range.

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.

Citation: Chen JF, Wu ZQ, Liu HS, Yan S, Wang YX, Xing M, Song XQ, Ding SY. Cumulative effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease in China. World J Gastroenterol 2024; 30(10): 1346-1357
URL: https://www.wjgnet.com/1007-9327/full/v30/i10/1346.htm
DOI: https://dx.doi.org/10.3748/wjg.v30.i10.1346