Effect of cholecystectomy on liver fat and fibrosis in metabolic dysfunction-associated steatotic liver disease patients

Table 1 Patient’s clinico-biological database, n (%)/median (interquartile range)

	Total (n = 213)	Chx+ (n = 103)	Chx- (n = 110)	P value
Sex male	107 (50.2)	31 (30.1)	76 (69.1)	< 0.001
Age (years)	51.66 ± 11.97	52.16 ± 10.97	51.51 ± 9.97	0.237
High blood pressure	102 (49.9)	54 (52.4)	48 (44)	0.139
Diabetes mellitus	104 (48.8)	41 (39.8)	63 (57.3)	0.008
Hypercholesterolemia	18 (8.5)	9 (8.7)	9 (8.2)	0.53
Hypertriglyceridemia	27 (12.7)	10 (9.7)	17 (15.5)	0.146
Metabolic syndrome	152 (71.4)	65 (63.1)	87 (79.1)	0.007
Weight (kg)	89.17 (54-136)	84.16 (54-123)	93.87 (56-136)	< 0.001
Size (cm)	169.28(150-190)	166.99 (154-190)	171.42 (150-188)	< 0.001
BMI (kg/m2)	31.06 (18.2-43.8)	30.16 (18.2-41.7)	31.9 (24.3-43.8)	0.002
Hip circumference (cm)	109.73 (78-140)	109.98 (78-140)	109.50 (80-136)	0.12
Waist size (cm)	108.65 (78-138)	107.62 (78-131)	109.62 (83- 138)	0.10
Chest perimeter (cm)	107.50 (80-128)	107.6 (80-126)	107.4 (80-128)	0.23
AST (UI/L)	29.95 (10.30-165.00)	29.47 (10.9-165)	30.40 (10.3- 89.0)	0.68
ALT (UI/L)	34.14 (7.0-161.0)	29.96 (7-161)	38.05 (9-117.65)	0.009
GGT (UI/L)	45.25 (8.9-299.3)	43.03 (8.9-299.3)	47.33 (12.46-211)	0.41
PAL (UI/L)	77.63 (21.13-370)	79.37(12-370)	76.00 (28.80-167)	0.44
prothrombin rate (%)	98.87 (80-100)	99.03(80-100)	98.71 (80-100)	0.53
Platelets (G mmol/L)	229.89 (89-502)	230.32(113-502)	229.50(89-470)	0.92
LDL Cholesterol (mmol/L)	2.95(0.67-5.89)	3.10(0.80-5.89)	2.81 (0.67-5.40)	0.02
HDL Cholesterol (mmol/L)	1.08 (0.21-4.10)	1.1(0.60-4.10)	1.07 (0.21-4.1)	0.72
Triglyceride (mmol/L)	1.82(0.58 15.24)	1.86(0.58-15.24)	1.79 (0.62-7.6)	0.70
HBA1c (%)	6.45 (4.2-10.35)	6.19(4.23-9.20)	6.69 (4.4-10.35)	0.001
Albumin (G/L)	44.42 (31.93-54.80)	44.42(33.02-54)	44.42(31.9-54.8)	0.99

Chx: Cholecystectomy; BMI: Body mass index; AST: Aspartate aminotransferase; ALT: Alanine amino transferase; GGT: Gamma glutamyl transferase; PAL: Phosphatase alkaline; LDL: Low density lipoprotein; HDL: High-density lipoprotein; HBA1c: Hemoglobin A1c.

Table 2 Biological and histological data, n (%)/median (interquartile range)/mean ± SE

Scores M0	Total (n = 213), mean (extreme)	Chx+ (n = 103), mean (extreme)	Chx- (n = 110), mean (extreme)	P value
BARD score	2.74 (0-4)	2.76 ± 1.04	2.72 (0-4)	0.79
HOMA test	7.879 (1.0-18.7)	7.37 ± 2.52	8.32 (2-18.7)	0.023
FLI score	78.52 (7-100)	75.71 ± 17.62	81.15 (31-100)	0.016
LAP score	82.73 (15.-372.40)	82.5 ± 40.09	82.94 (20.1-372.4)	0.94
HSI score	42.88 (25.2-79.4)	40.62 ± 5.76	44.99 (29.1-79.4)	< 0.001
APRI score	0.33 (0.1-2.8)	0.34 ± 0.32	0.33 (0.1-0.7)	0.67
FIB 4 score	2.64 (0.25-283.00)	4.16 ± 2.77	1.22 (0.25-3.73)	0.26
NFS score	-1.13 (-6.57 to 3.36)	-1.10 ± 1.44	-1.16 (-6.57 to 3.36)	0.78
Length LB (mm)	22.27 (10-45)	23.10 (10-45)	22.89 (10-45)	0.16
Portal area (n)	15.99 (6-28)	15.19 (6-28)	16.74 (7-28)	0.036
Steatosis (%)	29.53 (5-70)	23.79 (5-70)	34.90 (5-70)	< 0.001
NAS score	4.51 (1-8)	3.93 (1-8)	5.05 (2-8)	< 0.001
SAF score	6.36 (2-11)	5.56 (2-11)	7.11 (3-11)	< 0.001
Steatosis grade: S0	5 (2.3)	5 (4.9)	0	< 0.001
S1	114 (53.5)	68 (66)	46 (41.8)	< 0.001
S2	81 (38.0)	28 (27.2)	53 (48.2)	< 0.001
S3	13 (6.1)	2 (1.9)	11 (10)	< 0.001
Steatosis type: Absent	4 (1.9	4 (3.9)	0 (0)	0.007
Pure macrolobular	18 (8.5)	12 (11.7)	6 (5.5)	0.004
Pure microlobular	7 (3.3)	6 (5.8)	1 (0.9)	0.21
Mixed	184 (86.4)	81 (78.6)	103 (93.6)	0.003
Ballooning: Absent	23 (10.8)	15 (14.6)	8 (7.3)	0.001
Present (size = hepatocyte)	57 (26.8)	37 (35.9)	20 (18.2)	0.001
Present (size = hepatocyte 2n)	133 (62.4)	51 (49.5)	82 (74.5)	0.001
Apoptotic bodies: Absent or rare	162 (76.1)	89 (86.4)	73 (66.4)	0.001
Present	51 (23.9)	14 (13.6)	37 (33.6)	0.001
Mallory’s body: Absent	160 (75.1)	88 (85.4)	72 (65.5)	0.003
Present	52 (24.4)	15 (14.6)	37 (33.6)	0.003
Lobular inflammation: 0 foyer	21 (9.9)	14 (13.6)	7 (6.5)	< 0.001
1à 2 foyers	93 (43.7)	58 (56.3)	35 (31.8)	< 0.001
3 à 4 foyers	99 (46.5)	24 (23.3)	46 (41.8)	< 0.001
Portal inflammation: Absent	18 (8.5)	11 (10.7)	7 (6.4)	0.32
Present	195 (91.5)	92 (89.3)	103 (93.6)	0.32
MASH: Present	80 (37.6)	32 (31.06)	48 (43.63)	0.06
Absent	133 (62.4)	71 (68.9)	62 (56.4)	0.06
Classification Metavir (activity): Stade A1	54 (25.4)	34 (33.0)	20 (18.2)	< 0.001
Stade A2	135 (63.4)	66 (64.1)	69 (62.7)	< 0.001
Stade A3	24 (11.3)	3 (2.9)	21 (19.1)	< 0.001
Classification Metavir (fibrosis): Stade F0	6 (2.8)	5 (4.9)	1 (0.9)	< 0.001
Stade F1	29 (13.6)	24 (23.3)	5 (4.5)	< 0.001
Stade F2	144 (67.6)	67 (65.0)	77 (70)	< 0.001
Stade F3	26 (12.2)	5 (4.9)	21 (19.1)	< 0.001
Stade F4	8 (3.8)	2 (1.9)	6 (5.5)	< 0.001
Stiffness (kPa) MED	8.5 (5.3-24.5)	7.69 (5.3-14.2)	9.25 (7.2-24.5)	< 0.001
CAP (dB/m) MED	312.91 (180-400)	300.85 (180-400)	324.20 (224-400)	< 0.001
Elasticity (m/second)	1.11 (0.59-2.94)	1.01 (0.59-2.14)	1.20 (0.73-2.94)	< 0.001
Steatosis (%)	16.46 (3-50)	14.22 (3-40)	18.55 (4-50)	< 0.001

Chx: Cholecystectomy; BARD: Body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes mellitus; HOMA: Homeostasis model assessment; FLI: Fatty liver index; LAP: Lipid accumulation product; HSI: Hepatic steatosis index; APRI: Aspartate aminotransferase/platelet ratio index; FIB4: Fibrosis 4; NFS: Non-alcoholic fatty liver disease fibrosis score; LB: Liver biopsy; NAS: Non-alcoholic steatohepatitis activity score; MASH: Metabolic dysfunction-associated steatohepatitis; SAF: Steatosis, activity and fibrosis score; MED: Median stemness; CAP: Controlled attenuation parameter.

Table 3 Evolution of hepatic steatosis, mean ± SE

		M0	M36	P value M0 vs M36
CAP med (dB/m)	Chx: Yes	300.77 ± 47.42	314.17 ± 44.70	0.013
	Chx: No	325.06 ± 41.74	296.36 ± 56.51	< 0.001
Graisse hepatique/IRM (%)	Chx: Yes	14.22 ± 8.64	15.98 ± 7.93	< 0.001
	Chx: No	18.55 ± 8.57	13.88 ± 8.12	< 0.001

CAP: Controlled attenuation parameter; IRM: Siemens 3 Tesla Magnetom Vida 3T.

Table 4 Uni and multivariate analysis of risk factors associated with the presence of metabolic dysfunction-associated steatotic liver disease ≥ S2

Risk factor	Univariate			Multivariate
	OR	95%CI	P value	OR	95%CI	P value
Age ≥ 50 years	0.31	0.13-0.70	0.005	0.19	0.03-1.03	0.054
Sex female	1.68	0.97-2.90	0.062	1.40	0.52-3.70	0.86
High blood pressure	0.85	0.49-1.47	0.57	0.67	0.87-4.32	0.57
Diabetes mellitus	1.65	0.95-2.86	0.07	0.57	0.84-10.38	0.29
Hypertriglyceridemia	1.09	0.48-2.50	0.82	0.67	0.54-2.89	0.33
Hypercholesterolemia	0.98	0.35-2.74	0.97	0.78	0.45-4.23	0.42
Obesity	0.89	0.51-1.57	0.71	1.32	0.98-4.12	0.005
GBS	2.94	1.66-5.20	0.000	0.34	0.78-1.22	0.66
Chx	3.11	1.76-5.48	0.000	1.12	0.89-3.21	0.04
weight	0.96	0.94-0.98	0.01	0.98	0.45-3.21	0.57
BMI	1.08	1.01-1.16	0.01	0.92	1.12-4.27	0.49
Hip circumference (cm)	1.03	1.00-1.06	0.03	1.23	1.11-4.25	0.60
Waist size (cm)	2.10	1.11-3.94	0.02	2.95	0.84-10.38	0.008
Chest perimeter (cm)	2.86	1.53-5.32	0.001	0.65	0.89-3.74	0.93
GGT	1.38	0.77-2.46	0.27	0.87	0.65-5.12	0.90
Total cholesterol	0.72	0.33-1.56	0.41	0.65	0.87-4.22	0.26
LDL cholesterol	1.30	0.53-3.14	0.55	0.88	0.77-3.11	0.06
HbA1c	1.23	0.67-1.47	0.01	1.93	1.11-5.23	0.038
BARD score	0.57	0.27-1.18	0.13	0.65	0.55-2.11	0.35
Home test	1.54	0.27-8.65	0.61	0.34	0.44-3.25	0.69
FLI score	0.97	0.95-0.99	0.005	2.87	1.69-6.34	0.047
LAP score	1.40	0.39-4.95	0.59	0.99	0.89-4.11	0.23
HSI score	1.08	1.03-1.12	0.000	0.54	0.43-2.88	0.49
APRI score	1.32	0.44-3.95	0.61	0.56	0.55-2.33	0.21
FIB4 score	0.77	0.54-1.1	0.15	2.65	0.84-8.32	0.09
NFS score	0.84	0.70-1.00	0.06	1.83	0.65-5.13	0.60
Elasticity/ultrasound	3.52	1.53-8.06	0.003	7.00	0.68-71.40	0.10
Steatosis/MRI	1.27	1.19-1.36	0.000	10.21	3.65-28.52	< 0.001
Elasticity/FibroScan®	1.31	1.11-1.55	0.001	2.27	0.40-12.76	0.35
CAP	1.01	1.00-1.02	0.000	3.21	0.47-21.64	0.23

OR: Odds ratio; CI: Confidence interval; GBS: Gallbladder stones; Chx: Cholecystectomy; BMI: Body mass index; GGT: Gamma-glutamyl transferase; LDL: Low density lipoprotein; HbA1c: Hemoglobin A1c; BARD: Body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes mellitus; FLI: Fatty liver index; LAP: Lipid accumulation product; HSI: Hepatic steatosis index; APRI: Aspartate aminotransferase/platelet ratio index; FIB4: Fibrosis 4; NFS: Non-alcoholic fatty liver disease fibrosis score; MRI: Magnetic resonance imaging; CAP: Controlled attenuation parameter.

Table 5 Uni and multivariate analysis of risk factors associated with the presence of advanced fibrosis

Risk factor	Univariate			Multivariate
	OR	95%CI	P value	OR	95%CI	P value
Age ≥ 50 years	1.31	0.58-2.93	0.66	0.92	0.88-2.67	0.60
Sex female	0.73	0.41-1.29	0.28	0.45	0.33-1.65	0.88
High blood pressure	0.89	0.50-1.58	0.7	0.89	069-1.26	0.64
Diabetes mellitus	0.42	0.23-0.77	0.005	0.99	0.93-1.17	0.17
Hypertriglyceridemia	1.1	0.35-2.22	0.86	1.35	0.65-2.31	0.08
Hypercholesterolemia	1.56	0.55-4.39	0.85	1.79	1.89-2.91	0.09
Obesity	0.58	0.31-1.07	0.08	0.98	0.33-3.01	0.52
GBS	2.62	1.46-4.72	0.000	0.99	0.87-1.05	0.99
Chx	0.37	0.20-0.67	0.000	2.69	1.55-2.88	0.04
weight	0.96	0.94-0.98	0.038	0.99	0.87-1.76	0.93
BMI	0.91	0.86-0.97	0.01	0.86	069-1.06	0.18
Waist size (cm)	0.94	0.91-0.98	0.012	0.99	0.92-1.07	0.62
Metabolic syndrome	0.32	0.15-0.69	0.004	0.51	0.16-1.64	0.26
ALT	0.94	0.91-0.97	0.003	0.99	0.23-3.01	0.79
GGT	0.98	0.96-1.00	0.02	0.99	0.97-1.05	0.53
Triglycerides	1.05	0.72-1.55	0.27	1.75	1.09-2.81	0.07
LDL Cholesterol	1.24	0.83-1.87	0.22	1.32	0.99-2.43	0.09
BARD score	1.12	0.79-1.59	0.30	1.78	0.99-2.67	0.03
Home test	0.90	0.78-1.04	0.18	0.89	0.77-2.31	0.29
FLI score	0.97	0.95-0.99	0.02	1.01	0.97-1.05	0.42
LAP score	0.99	0.98-1.00	0.48	0.87	0.77-1.88	0.58
HSI score	0.90	0.84-0.96	0.000	0.96	0.85-1.07	0.48
APRI score	1.73	0.01-2.22	0.178	0.89	0.47-2.99	0.65
FIB4 score	0.96	0.59-1.57	0.93	0.99	1.32-3.46	0.55
NFS score	0.95	0.75-1.21	0.95	0.32	0.44-1.21	0.50
Elasticity/ultrasound	0.027	0.003-0.22	0.000	2.65	4.27-1.65	0.09
Steatosis/MRI	0.89	0.84-0.95	0.000	0.13	0.03-0.58	0.712
Elasticity/FibroScan®	0.09	0.04-0.20	0.000	0.98	0.88-1.87	0.006
CAP	0.99	0.98-1.00	0.000	0.43	0.56-1.12	0.4

OR: Odds ratio; CI: Confidence interval; GBS: Gallbladder stones; Chx: Cholecystectomy; BMI: Body mass index; GGT: Gamma-glutamyl transferase; LDL: Low density lipoprotein; HbA1c: Hemoglobin A1c; BARD: Body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes mellitus; FLI: Fatty liver index; LAP: Lipid accumulation product; HSI: Hepatic steatosis index; APRI: Aspartate aminotransferase/platelet ratio index; FIB4: Fibrosis 4; NFS: Non-alcoholic fatty liver disease fibrosis score; MRI: Magnetic resonance imaging; CAP: Controlled attenuation parameter.

Table 6 Uni and multivariate analysis of risk factors associated with the presence of metabolic dysfunction-associated steatohepatitis

Risk factor	Univariate			Multivariate
	OR	95%CI	P value	OR	95%CI	P value
Age ≥ 50 years	1.00	0.98-1.03	0.93	0.77	0.87-1.65	0.2
Sex female	0.98	0.56-1.71	0.80	0.89	0.77-1.34	0.45
High blood pressure	0.96	0.55-1.67	0.93	0.98	0.89-2.11	0.10
Diabetes mellitus	0.50	0.28-0.89	0.01	1.03	0.87-1.22	0.69
Hypertriglyceridemia	0.97	0.42-2.24	0.91	0.78	0.98-4.22	0.64
Hypercholesterolemia	1.74	0.66-4.60	0.99	0.89	0.78-2.23	0.79
Obesity	1.35	0.76-2.38	0.24	1.92	0.92-1.13	0.04
GBS	0.58	0.33-1.02	0.04	0.67	0.77-1.11	0.056
Chx	0.58	0.33-1.02	0.059	1.43	0.87-1.37	0.05
weight	0.99	0.97-1.01	0.76	0.78	0.66-1.21	0.89
BMI	0.98	0.92-1.05	0.73	1.03	0.87-1.22	0.69
Waist size (cm)	0.98	0.95-1.01	0.22	0.99	0.92-1.06	0.82
Metabolic syndrome	2.04	1.06-3.93	0.07	1.40	0.45-4.36	0.55
ALT	0.97	0.96-0.99	0.002	0.60	0.20-1.78	0.68
GGT	0.99	0.98-1.00	0.27	1.87	0.98-2.11	0.02
Triglycerides	0.91	0.68-1.22	0.59	0.68	0.28-1.22	0.17
LDL Cholesterol	0.94	0.69-1.27	0.92	0.56	0.69-3.36	0.47
BARD score	1.18	0.91-1.53	0.27	0.79	0.54-2.86	0.06
Home test	0.91	0.83-1.01	0.06	0.86	0.47-1.38	0.45
FLI score	0.98	0.96-1.00	0.07	0.79	0.64-1.66	0.13
LAP score	1.00	0.99-1.00	0.80	0.34	0.87-1.33	0.75
HSI score	0.94	0.91-0.98	0.006	0.78	0.88-1.65	0.76
APRI score	0.50	0.15-1.63	0.30	0.88	0.98-3.22	0.97
FIB4 score	1.14	0.78-1.66	0.53	0.56	0.67-1.33	0.24
NFS score	1.04	0.87-1.25	0.50	0.76	0.54-2.66	0.76
Elasticity/ultrasound	0.26	0.11-0.59	0.001	0.89	0.77-1.76	0.16
Steatosis/MRI	0.88	0.85-0.92	0.000	1.89	0.99-1.26	< 0.001
Elasticity/FibroScan®	0.70	0.58-0.83	0.000	1.65	1.22-3.67	0.043
CAP	0.98	0.98-0.99	0.000	1.45	1.17-3.25	0.121

OR: Odds ratio; CI: Confidence interval; GBS: Gallbladder stones; Chx: Cholecystectomy; BMI: Body mass index; GGT: Gamma-glutamyl transferase; LDL: Low density lipoprotein; HbA1c: Hemoglobin A1c; BARD: Body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes mellitus; FLI: Fatty liver index; LAP: Lipid accumulation product; HSI: Hepatic steatosis index; APRI: Aspartate aminotransferase/platelet ratio index; FIB4: Fibrosis 4; NFS: Non-alcoholic fatty liver disease fibrosis score; MRI: Magnetic resonance imaging; CAP: Controlled attenuation parameter.