Immunometabolic drivers of metabolic dysfunction-associated steatotic liver disease in non-obese people living with human immunodeficiency virus

doi:10.3748/wjg.120036

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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

Observational Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastroenterol. Nov 7, 2026; 32(41): 120036
Published online Nov 7, 2026. doi: 10.3748/wjg.120036

Table 1 Demographic and clinical characteristics of the total population, mean ± SD/n (%)/median (interquartile range)

Variables	Total (n = 181)	Non-MASLD (n = 97)	MASLD (n = 84)	P value
Age, years	40 (35-48)	39 (34-46)	41 (36-52)	< 0.05
Gender				0.57
Male	172 (95.0)	93 (95.9)	79 (94.1)
Female	9 (5.0)	4 (4.1)	5 (6.0)
Weight, kg	72.9 ± 12.6	65.5 ± 8.9	81.5 ± 10.6	< 0.001
BMI, kg/m²	24.0 ± 3.6	21.7 ± 2.1	26.7 ± 3.1	< 0.001
ALT, U/L	25.0 (17.8-34.0)	21.5 (16.0-30.0)	28.0 (21.0-41.8)	< 0.001
Glucose, mmol/L	5.3 (5.0-5.7)	5.2 (5.0-5.5)	5.5 (5.1-5.9)	< 0.01
UA, μmol/L	366.5 ± 90.9	350.8 ± 83.6	384.2 ± 95.9	< 0.05
LDL, mmol/L	2.9 ± 0.7	2.8 ± 0.7	2.9 ± 0.7	0.57
HDL, mmol/L	1.2 (1.0-1.4)	1.3 (1.2-1.5)	1.1 (0.9-1.2)	< 0.001
TG, mmol/L	1.4 (1.0-2.2)	1.2 (0.9-1.9)	1.5 (1.1-2.8)	< 0.01
TC, mmol/L	4.7 (4.0-5.4)	4.6 (4.0-5.3)	4.9 (4.0-5.7)	0.16
TyG index	7.1 (6.8-7.7)	7.0 (6.6-7.5)	7.3 (6.9-7.8)	< 0.01
TC/HDL	4.0 (3.4-4.8)	3.6 (2.9-4.2)	4.5 (3.6-5.2)	< 0.001
UAP, dB/m	253.6 (226.4-272.1)	227.1 (216.1-240.2)	276.1 (262.5-291.1)	< 0.001
LSM, kPa	5.4 (4.61-6.6)	5.1 (4.4-5.9)	5.9 (5.0-7.1)	< 0.001
Duration, months	63.2 (48.7-93.2)	69.3 (50.4-93.5)	60.8 (48.6-95.1)	0.72
Initial HVL, copies/mL	50149.0 (22723.0-185078.5)	50149.0 (23000.0-175952.0)	49541.5 (22418.3-222100.3)	0.91
Initial CD4 cell count, cells/μL	276.1 ± 177.7	262.5 ± 174.5	292.2 ± 181.2	0.28
CD4 cell count, cells/μL	562.0 (399.5-677.0)	562.0 (378.0-694.0)	568.0 (439.3-665.0)	0.43
CD4 cell count ≥ 300 cells/μL				< 0.05
No	53 (29.3)	35 (36.1)	18 (21.4)
Yes	128 (70.7)	62 (63.9)	66 (78.7)
CD4/CD8 ratio	0.8 (0.6-1.1)	0.7 (0.5-1.1)	0.8 (0.6-1.1)	0.30
Group				0.26
INSTIs	76 (42.0)	42 (43.3)	34 (40.5)
Switch	32 (17.8)	13 (13.4)	19 (22.6)
Non-INSTIs	73 (40.3)	42 (43.3)	31 (36.9)
Drinking				0.86
No	175 (96.7)	94 (96.9)	81 (96.4)
Yes	6 (3.3)	3 (3.1)	3 (3.6)
Smoking				0.48
No	178 (98.3)	96 (99.0)	82 (97.6)
Yes	3 (1.7)	1 (1.0)	2 (2.4)
Hypertension				0.82
No	154 (85.1)	89 (91.8)	65 (77.4)
Yes	27 (14.9)	8 (8.3)	19 (22.6)
Diabetes				< 0.01
No	173 (95.6)	95 (97.9)	78 (92.9)
Yes	8 (4.4)	2 (2.1)	6 (7.1)
Lipid lowering drug				0.05
No	171 (94.5)	92 (94.9)	79 (94.1)
Yes	10 (5.5)	5 (5.2)	5 (6.0)
Antihypertensive drug				0.86
No	158 (87.3)	92 (94.9)	66 (78.6)
Yes	23 (12.7)	5 (5.2)	18 (21.4)
Hypoglycemic drug				0.48
No	172 (95.0)	95 (97.9)	77 (91.7)
Yes	9 (5.0)	2 (2.1)	7 (8.3)

Due to rounding, percentages may not add up to 100%. MASLD: Metabolic dysfunction-associated steatotic liver disease; BMI: Body mass index; ALT: Alanine aminotransferase; UA: Uric acid; LDL: Low-density lipoprotein; HDL: High-density lipoprotein; TG: Triglycerides; TC: Total cholesterol; TyG: Triglyceride-glucose; CD: Cluster of differentiation; UAP: Ultrasound attenuation parameter; LSM: Liver stiffness measurement; HVL: Human immunodeficiency virus viral load; INSTIs: Integrase strand transfer inhibitors-based regime group; Switch: Switching-to-integrase strand transfer inhibitors-based regime groups; Non-INSTIs: Non-integrase strand transfer inhibitors-based regime group.

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Table 2 Demographic and clinical characteristics of non-obese participants with metabolic dysfunction-associated steatotic liver disease and non-metabolic dysfunction-associated steatotic liver disease, mean ± SD/n (%)/median (interquartile range)

Variables	Non-MASLD (n = 91)	MASLD (n = 24)	P value
Age, years	39 (33-46)	39 (36-49)	0.35
Gender			0.30
Male	87 (95.6)	24 (100.0)
Female	4 (4.4)	0 (0.0)
Weight, kg	64.9 ± 8.7	70.9 ± 5.9	< 0.001
BMI, kg/m²	21.5 (20.1-23.4)	23.2 (22.8-24.4)	< 0.001
ALT, U/L	21.0 (16.0-29.0)	31.0 (21.3-54.3)	< 0.01
Glucose, mmol/L	5.2 (5.0-5.5)	5.5 (5.1-5.9)	< 0.05
UA, μmol/L	349.5 ± 85.1	377.2 ± 71.5	0.15
LDL, mmol/L	2.8 ± 0.7	2.8 ± 0.7	0.82
HDL, mmol/L	1.3 (1.2-1.5)	1.0 (0.9-1.2)	< 0.001
TG, mmol/L	1.2 (0.9-1.9)	1.9 (1.1-3.2)	< 0.05
TC, mmol/L	4.6 (4.1-5.3)	4.9 (4.1-5.8)	0.25
UAP, dB/m	228.5 ± 20.9	264.2 ± 11.9	< 0.001
LSM, kPa	5.1 (4.4-5.9)	5.1 (4.4-6.7)	0.29
Duration, months	67.5 (50.2-93.1)	75.6 (58.4-107.9)	0.17
Group			0.58
INSTIs	40 (44.0)	8 (33.3)
Switch	13 (14.3)	5 (20.8)
Non-INSTIs	38 (41.8)	11 (45.8)
TyG index	7.1 ± 0.7	7.5 ± 0.7	< 0.01
TC/HDL	3.6 (2.9-4.2)	4.6 (3.6-5.5)	< 0.001
Initial HVL, copies/mL	46899.5 (21446.5-141112.5)	30761.5 (14159.0-177755.8)	0.48
Initial CD4 cell count, cells/μL	269.2 ± 176.7	279.1 ± 125.1	0.80
CD4 cell count, cells/μL	559.0 (376.0-682.0)	519.0 (428.8-672.8)	0.51
CD4 cell count ≥ 350 cells/μL			< 0.01
No	33 (36.3)	1 (4.2)
Yes	58 (63.7)	23 (95.8)
CD4/CD8 ratio	0.7 (0.5-1.1)	0.9 (0.6-1.4)	< 0.05
Drinking			0.84
No	88 (96.7)	23 (95.8)
Yes	3 (3.3)	1 (4.2)
Smoking			0.61
No	90 (98.9)	24 (100.0)
Yes	1 (1.1)	0 (0.0)
Hypertension			< 0.05
No	85 (93.4)	19 (79.2)
Yes	6 (6.6)	5 (20.8)
Diabetes			0.46
No	89 (97.8)	24 (100.0)
Yes	2 (2.2)	0 (0.0)
Lipid lowering drug			0.14
No	87 (95.6)	21 (87.5)
Yes	4 (4.4)	3 (12.5)
Antihypertensive drug			< 0.05
No	88 (96.7)	20 (83.3)
Yes	3 (3.3)	4 (16.7)
Hypoglycemic drug			0.46
No	89 (97.8)	24 (100.0)
Yes	2 (2.2)	0 (0.0)

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Table 3 Multivariable analysis of factors associated with metabolic dysfunction-associated steatotic liver disease among non-obese people living with human immunodeficiency virus

Variables	Univariate analysis		Multivariable analysis
Variables	P value	Crude OR (95%CI)	P value	Adjusted OR (95%CI)
Age	0.34	1.05 (0.96-1.14)
Gender	1.00	137533244.9 (0-.)¹
Group
INSTIs	0.75
Switch	0.46	1.85 (0.36-9.48)
Non-INSTIs	0.67	1.56 (0.20-11.92)
BMI	0.004	2.03 (1.26-3.26)	0.002	2.14 (1.32-3.47)
ALT	0.027	1.04 (1.00-1.07)	0.032	1.04 (1.003-1.069)
HDL	0.015	0.01 (0-0.37)	0.028	0.03 (0.001-0.688)
Glucose	0.20	0.68 (0.38-1.22)
TyG index	0.06	3.31 (0.93-11.75)	0.043	3.29 (1.04-10.40)
CD4 cell count ≥ 350 cells/μL	0.19	5.88 (0.42-100.00)
CD4/CD8 ratio	0.19	4.21 (0.49-35.84)	0.013	8.55 (1.57-46.66)

¹The extreme odds ratio for gender results from complete separation caused by the limited number of female participants (n = 4, all in the non-metabolic dysfunction-associated steatotic liver disease group). The upper bound of the 95% confidence interval is not estimable.

Variables included gender, age, group, body mass index, alanine aminotransferase, high-density lipoprotein, triglyceride-glucose, glucose, cluster of differentiation (CD) 4 cell count ≥ 350 cells/μL, and CD4/CD8 ratio. OR: Odds ratio; CI: Confidence interval; BMI: Body mass index; ALT: Alanine aminotransferase; HDL: High-density lipoprotein; TyG: Triglyceride-glucose; CD: Cluster of differentiation; INSTIs: Integrase strand transfer inhibitors-based regime group; Switch: Switching-to-integrase strand transfer inhibitors-based regime groups; Non-INSTIs: Non-integrase strand transfer inhibitors-based regime group.

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Table 4 Multivariable analysis of factors associated with liver steatosis among non-obese people living with human immunodeficiency virus with cluster of differentiation 4/cluster of differentiation 8 ratio ≥ 1 and < 1

Variables	CD4/CD8 ratio ≥ 1		CD4/CD8 ratio < 1
Variables	P value	Adjusted OR (95%CI)	P value	Adjusted OR (95%CI)
BMI	0.008	3.01 (1.34-6.76)	0.026	1.73 (1.07-2.80)
HDL			0.016	0.01 (0.00-0.40)
CD4 cell count ≥ 350 cells/μL			0.031	13.00 (1.27-125.00)

Variables included gender, age, group, body mass index, alanine aminotransferase, high-density lipoprotein, triglyceride-glucose, glucose, and cluster of differentiation 4 cell count ≥ 350 cells/μL in models 1 and 2. OR: Odds ratio; CI: Confidence interval; CD: Cluster of differentiation; BMI: Body mass index; HDL: High-density lipoprotein.

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Table 5 Longitudinal changes in key metabolic, immunological, and hepatic parameters across three antiretroviral therapy regimens (mixed-effects model results), mean ± SD

Characteristics	Group	Baseline	Month 6	Month 12	P value for time effect	P value for group effect	P value for time × group effect
UAP, dB/m	INSTIs	237.6 ± 24.5 (n = 47)	238.4 ± 24.3 (n = 30)	236.1 ± 23.5 (n = 21)	0.8	0.087	0.583
	Switch	239.1 ± 24.4 (n = 19)	243.3 ± 19.0 (n = 15)	237.1 ± 20.6 (n = 15)
	Non-INSTIs	233.2 ± 24.0 (n = 49)	224.7 ± 27.1 (n = 24)	228.6 ± 28.8 (n = 28)
LSM, kPa	INSTIs	5.4 ± 1.4 (n = 47)	6.1 ± 3.2 (n = 30)	5.8 ± 0.9 (n = 21)	0.911	0.872	0.552
	Switch	6.0 ± 2.9 (n = 19)	6.4 ± 2.6 (n = 15)	6.2 ± 3.7 (n = 15)
	Non-INSTIs	5.3 ± 1.3 (n = 49)	5.4 ± 1.2 (n = 24)	5.5 ± 1.1 (n = 28)
ALT, U/L	INSTIs	24.9 ± 16.0 (n = 43)	26.1 ± 16.2 (n = 28)	31.4 ± 16.7 (n = 25)	0.587	0.19	0.999
	Switch	28.0 ± 15.7 (n = 17)	26.4 ± 12.8 (n = 16)	29.6 ± 24.5 (n = 12)
	Non-INSTIs	33.3 ± 26.5 (n = 43)	33.2 ± 28.7 (n = 30)	34.6 ± 26.9 (n = 22)
BMI, kg/m²	INSTIs	22.0 ± 2.3 (n = 47)	22.7 ± 2.2 (n = 30)	22.5 ± 2.3 (n = 21)	< 0.01	0.258	0.057
	Switch	22.0 ± 1.8 (n = 19)	22.7 ± 1.6 (n = 15)	23.1 ± 1.6 (n = 15)
	Non-INSTIs	21.6 ± 1.9 (n = 49)	22.0 ± 1.6 (n = 23)	22.2 ± 1.8 (n = 28)
HDL, mmol/L	INSTIs	1.5 ± 0.8 (n = 43)	1.6 ± 0.9 (n = 29)	1.5 ± 0.7 (n = 24)	0.323	< 0.01	0.979
	Switch	1.4 ± 0.6 (n = 17)	1.4 ± 0.6 (n = 17)	1.2 ± 0.2 (n = 10)
	Non-INSTIs	1.2 ± 0.3 (n = 42)	1.3 ± 0.6 (n = 31)	1.2 ± 0.3 (n = 24)
Glucose, mmol/L	INSTIs	5.2 ± 0.5 (n = 43)	5.3 ± 0.4 (n = 29)	5.0 ± 0.9 (n = 22)	0.056	< 0.05	0.357
	Switch	5.9 ± 2.0 (n = 17)	5.5 ± 0.5 (n = 17)	5.3 ± 0.3 (n = 9)
	Non-INSTIs	5.6 ± 1.3 (n = 43)	5.5 ± 0.4 (n = 31)	5.5 ± 0.3 (n = 19)
TyG index	INSTIs	7.1 ± 0.7 (n = 40)	7.4 ± 0.9 (n = 28)	6.9 ± 0.5 (n = 17)	< 0.05	0.572	0.057
	Switch	7.2 ± 0.9 (n = 15)	7.0 ± 0.4 (n = 16)	6.7 ± 0.3 (n = 8)
	Non-INSTIs	7.2 ± 0.6 (n = 42)	7.1 ± 0.4 (n = 25)	7.1 ± 0.6 (n = 14)
CD4/CD8 ratio	INSTIs	0.8 ± 0.4 (n = 43)	0.8 ± 0.4 (n = 29)	0.8 ± 0.4 (n = 25)	0.324	0.452	0.322
	Switch	1.0 ± 0.5 (n = 17)	1.0 ± 0.5 (n = 16)	0.9 ± 0.4 (n = 12)
	Non-INSTIs	0.9 ± 0.4 (n = 44)	0.8 ± 0.3 (n = 29)	0.9 ± 0.4 (n = 22)
CD4 cell count, cells/μL	INSTIs	522.7 ± 204.6 (n = 42)	570.9 ± 188.2 (n = 29)	524.8 ± 180.2 (n = 27)	0.381	0.101	0.81
	Switch	647.9 ± 241.0 (n = 17)	656.7 ± 262.7 (n = 16)	613.5 ± 224.2 (n = 13)
	Non-INSTIs	533.9 ± 224.4 (n = 44)	534.7 ± 226.9 (n = 29)	487.5 ± 229.5 (n = 24)

Number of patients with non-missing data at each time point. UAP: Ultrasound attenuation parameter; LSM: Liver stiffness measurement; ALT: Alanine aminotransferase; BMI: Body mass index; HDL: High-density lipoprotein; TyG: Triglyceride-glucose; CD: Cluster of differentiation; INSTIs: Integrase strand transfer inhibitors-based regime group; Switch: Switching-to-integrase strand transfer inhibitors-based regime groups; Non-INSTIs: Non-integrase strand transfer inhibitors-based regime group.

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Citation: Ji F, Zhang LF, Gui Y, Qi ZH, Han Y, Su N, Zhang Q, Li YL, Zhao W, Lyu W, Yang M. Immunometabolic drivers of metabolic dysfunction-associated steatotic liver disease in non-obese people living with human immunodeficiency virus. World J Gastroenterol 2026; 32(41): 120036
URL: https://www.wjgnet.com/1007-9327/full/v32/i41/120036.htm
DOI: https://dx.doi.org/10.3748/wjg.120036

Ji F, Zhang LF, Gui Y, Qi ZH, Han Y, Su N, Zhang Q, Li YL, Zhao W, Lyu W, Yang M. Immunometabolic drivers of metabolic dysfunction-associated steatotic liver disease in non-obese people living with human immunodeficiency virus. World J Gastroenterol 2026; 32(41): 120036 [DOI: 10.3748/wjg.120036]

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