Ursodeoxycholic acid as a means of preventing atherosclerosis, steatosis and liver fibrosis in patients with nonalcoholic fatty liver disease

Table 1 Baseline characteristics of the study patients

Parameter	Total sample (n = 174)	Men (n = 121)	Women (n = 53)	P value
Age, years, Ме (IQR)	45.2 ± 10.1	42.9 ± 8.7	50.7 ± 10.5	< 0.001
T2DM	54 (31.0)	35 (28.9)	19 (35.8)	0.466
AH	41 (23.6)	27 (22.3)	14 (26.4)	0.695
Smoking	58 (33.3)	45 (37.2)	13 (24.5)	0.146
Obesity, classes I-III	121 (69.5)	79 (65.3)	42 (79.2)	0.097
Metabolic syndrome, NCEP ATP III	79 (45.4)	45 (37.2)	34 (64.2)	0.002

Data are presented as mean ± SD or n (%). Me: Median; IQR: Interquartile range; T2DM: Type 2 diabetes mellitus; AH: Arterial hypertension; NCEP ATP III: National cholesterol education program adult treatment panel III.

Table 2 Changes in clinical variables and liver function tests from baseline during the trial

Parameter	Baseline	3 mo	6 mo
Weight (total sample), kg	94.8 (86.7; 102.1)	93.0 (86.0; 100.0)c	92.9 (85.0; 98.3)c
Men	95.0 (92.0; 104.2)	94.0 (90; 101.1)c	93.7 (88.7; 100.0)c
Women	86.7 (82.0; 96.0)	85.0 (80.0; 94.8)c	85.0 (79.0; 95.0)b
∆ total sample, kg		-1.0 (-2.4; 0.0)	-1.0 (-2.4; 0.0)
Weight loss > 5% (total sample)		11 (6.3)	54 (31)c
Men		8 (6.6)	39 (32.2)c
Women		3 (5.6)	15 (28.3)b
BMI (total sample), kg/m2	31.2 (29.4; 34.0)	30.9 (29.3; 33.3)c	30.6 (29.0; 33.1)c
Men	30.7 (29.0; 33.3)	30.4 (29.0; 32.6)c	30.1 (28.4; 32)c
Women	32.0 (30.7; 36.2)	31.5 (30.1; 34.6)c	31.6 (29.7; 34.4)b
∆ total sample, kg/m2		-0.4 (-0.9; 0.0)	-0.3 (-0.8; 0.0)
Waist circumference (total sample), cm	102.0 (97.0; 111.8)	100.0 (96.0; 108.0)c	100.0 (94.0; 106.0)c
Men	103.0 (98.0; 112.0)	102.0 (97.0; 110.0)c	100 (97.0; 106.0)c
Women	99.0 (93.0; 106.0)	98.0 (92.0; 105.0)c	97.0 (90.0; 102.0)c
∆ total sample, сm		-2.0 (-3.0; 0.0)	0.0 (-2.0; 0.0)c
ALT (total sample), U/L	53.0 (34.0; 78.0)	35.0 (26.0; 45.0)c	29.0 (24.0; 38.0)c
Men	55.8 (37.0; 78.0)	38.0 (29.0; 46.0)c	32.0 (25.9; 41.0)c
Women	44.0 (30.8; 69.0)	28.5 (21.6; 38.0)c	26.0 (16.5; 33.2)c
∆ total sample, U/L		-14.1 (-31.0; -5.3)	-6.5 (-14.0; 0.1)c
ALT (total sample) 10-19.9/20-39.9/≥ 40 U/L	5 (2.8)/53 (30.5)/116 (66.7)	15 (8.6)/95 (54.6)/64(36.8)b	26 (14.9)/108 (62.1)/40 (23.0)c
Men	1 (0.8)/35 (28.9)/85 (70.2)	5 (4.1)/64 (52.9)/52 (43)c	10 (8.3)/79 (65.3)/32 (26.4)a
Women	4 (7.5)/18 (34)/31 (58.5)	10 (18.9)/31 (58.5)/12 (22.6)c	16 (30.2)/29 (54.7)/8 (15.1)
AST (total sample), U/L	31.0 (24.0; 42.0)	26.5 (21.0; 34.0)c	25.0 (21.0; 29.0)c
Men	29.1 (23.5; 42.0)	26.0 (21.0; 33.0)c	25.0 (21.0; 28.0)c
Women	32.0 (24.0; 42.0)	28.0 (22.0; 35.0)c	26.0 (23.0; 32.0)
∆ total sample, U/L		-4.0 (-12.0; 1.0)	-2.0 (-7.0; 2.2)b
GGT (total sample), U/L	36.0 (26.0; 48.0)	28.0 (21.0; 38.0)c	26.0 (19.0; 35.0)c
Men	36.0 (28.0; 46.0)	31.0 (24.0; 41.0)c	26.0 (21.0; 35.0)c
Women	35.0 (23.0; 53.0)	23.0 (18.0; 30.0)c	21.0 (12.0; 34.0)
∆ total sample, U/L		-5.0 (-15.0; 2.0)	-3.0 (-8.0; 2.0)c

^aP < 0.05.

^bP < 0.01.

^cP < 0.001. Data are presented as median (IQR) or n (%). BMI: Body mass index; ALT: Alanine aminotransferase; AST: Aspartate transaminase; GGT: Glutamyltransferase.

Table 3 Changes in laboratory and imaging variables from baseline during the trial

Parameter	Baseline	6 mo	P value
ТС (total sample), mmol/L	6.03 ± 1.36	5.76 ± 1.21	< 0.001
Men	5.99 ± 1.39	5.77 ± 1.24	0.003
Women	6.11 ± 1.32	5.73 ± 1.16	0.019
LDL (total sample), mmol/L	3.86 ± 1.01	3.66 ± 0.91	< 0.001
Men	3.81 ± 1.04	3.67 ± 0.90	0.033
Women	4.0 ± 0.94	3.65 ± 0.93	0.006
HDL (total sample), mmol/L	1.24 ± 0.32	1.24 ± 0.27	0.910
Men	1.24 ± 0.33	1.21 ± 0.22	0.160
Women	1.23 ± 0.29	1.31 ± 0.34	0.036
TG (total sample), mmol/L	3.18 (2.00; 4.29)	2.04 (1.40; 3.16)	< 0.001
Men	3.13 (2.10; 4.29)	2.04 (1.4; 2.79)	< 0.001
Women	3.45 (1.80; 4.36)	2.26 (1.35; 3.62)	< 0.001
FLI (total sample)	84.9 ± 10.4	72.3 ± 17.6	< 0.001
Men	86.3 ± 9.0	73.6 ± 17.2	< 0.001
Women	81.9 ± 12.7	69.4 ± 18.4	< 0.001
FLI (total sample) ≥ 60/30-59/< 30	174 (100)/-/-	133 (76.4)/40 (23.0)/1 (0.6)	< 0.001
Men	121 (100)/-/-	96 (79)/24 (20)/1 (1)	< 0.001
Women	53 (100)/-/-	37 (70)/16 (30)/-	< 0.001
NFS (total sample) < -1.455 (F0-F2), n (%)	141 (81.0)	148 (85.0)	0.353
Men	102 (84.3)	112 (92.6)	0.071
Women	39 (76.6)	34 (64.2)	0.402
FIB 4 (total sample) < 1.45 (F0-F1), n (%)	157 (90.2)	163 (93.7)	0.256
Men	111 (91.7)	114 (94.2)	0.615
Women	46 (86.8)	49 (92.5)	0.402
CIMT (total sample), mm	0.985 ± 0.243	0.968 ± 0.237	0.013
Men	0.993 ± 0.224	0.977 ± 0.217	0.073
Women	0.967 ± 0.284	0.947 ± 0.276	0.052
CIMT (total sample) exceeding ULN for the corresponding age and sex	143 (84)	139 (82)	0.549
Men	103 (85.1)	101 (83.5)	0.860
Women	40 (75.5)	38 (72)	0.826
ASCVD (total sample, n = 112) 10-year risk	5.1 (2.9; 9.1)	4.8 (2.6; 8.0)	0.053
Men (n = 71)	6.0 (3.6; 11.1)	5.8 (3.4; 8.8)	0.720
Women (n = 41)	3.5 (2.3; 7.8)	3.2 (2.0; 6.0)	0.003
ASCVD (total sample, n = 152) lifetime risk	50 (39; 60)	50 (39; 64)	0.370
Men (n = 112)	50 (46; 69)	50 (46; 69)	0.870
Women (n = 40)	39 (39; 50)	39 (39; 50)	0.160

Data are presented as median (IQR) or n (%). ТС: Total cholesterol; LDL: Low-density lipoprotein; HDL: High-density lipoprotein; TG: Triglyceride; FLI: Fatty liver index; NFS: Nonalcoholic fatty liver disease fibrosis score; FIB-4: Liver fibrosis index; ULN: Upper limit of normal; ASCVD: Atherosclerotic Cardiovascular Disease.

Table 4 Comparison of the parameter decrease degree in subgroups with weight loss of more and less than 5% from baseline to the end of treatment

Parameter	Weight loss > 5% (n = 54)	Weight loss ≤ 5% (n = 120)	P value
∆ALT, U/L	-21.1 (-45.0; -6.0)	-25.0 (-42.5; -6.0)	0.683
∆ALT, %	-46 (-63; -18)	-43 (-54; -23)	0.281
∆AST, U/L	-6.0 (-15.0; 1.6)	-5.0 (-18.0; 1.0)	0.673
∆AST, %	22 (-41; 0)	-17 (-42; 0)	0.446
∆GGT, U/L	-5.0 (-17.0; 0)	-8.0 (-22.5; 0)	0.492
∆GGT, %	-19 (-41; 0)	-32 (-50; 0)	0.354
∆TC, mmol/L	-0.10 (-0.66; 0.30)	-0.10 (-0.57; 0.2)	0.666
∆TG, mmol/L	-1.04 (-1.80; -0.23)	-0.70 (-1.33; -0.11)	0.079
∆LDL, mmol/L	-0.20 (-0.7; 0.2)	-0.14 (-0.58; 0.3)	0.401
FLI
Initially	88.3 ± 10.2	83.5 ± 10.3	0.002
After 6 mo	71.4 ± 19.6c	72.8 ± 16.7c	0.916
∆FLI	-14.6 (-21.8; -6.3)	-8.45 (-17.9; -2)	0.003

^cP < 0.001. ∆ is the difference in indicators after 6 mo and at baseline. The minus sign indicates a decrease in the parameter by the end of the study.