Lipid-Lowering Responses to Dyslipidemia Determine the Efficacy on Liver Enzymes in Metabolic Dysfunction-Associated Fatty Liver Disease with Hepatic Injuries: A Prospective Cohort Study

Figures & data

Table 1 Comparison of Clinical and Laboratory Characteristics at Baseline and the 12th Month Between Lipid-Lowering Group and Control Group

Characteristics	Lipid-Lowering Group (n=325)			Control Group (n=216)			Baseline Comparison
	Baseline	12 Months	P	Baseline	12 Months	P	P
Male, n (%)	241 (74.2)	-	-	167 (77.3)	-	-	0.403
Age, years	41.9±12.8	-	-	41.4±12.6	-	-	0.677
Weight, kg	72.6±12.9	71.6±12.5	0.348	73.7±11.5	73.3±11.7	0.733	0.286
BMI, kg/m^2	26.0±3.5	25.5±3.4	0.100	26.0±3.1	26.0±3.3	0.892	0.273
WC, cm	88.4±9.3	87.4±8.8	0.248	89.3±8.2	89.3±8.8	0.962	0.841
SBP, mmHg	129±16	129±16	0.995	128±16	128±15	0.944	0.583
DBP, mmHg	84±13	84±13	0.928	83±13	83±12	0.912	0.582
Hypertension, n (%)	147 (45.2)	-	-	98 (45.4)	-	-	0.975
T2DM, n (%)	67 (20.6)	-	-	41 (19.0)	-	-	0.641
ALT, U/L	80±37	26±15	<0.001	78±34	74±33	0.145	0.570
AST, U/L	52±31	25±13	<0.001	53±33	49±22	0.100	0.686
GGT, U/L	89±61	40±19	<0.001	89±58	82±41	0.090	0.920
TC, mmol/L	6.1±1.3	3.6±0.7	<0.001	6.0±1.0	5.9±1.1	0.611	0.190
TG, mmol/L	3.1±1.9	1.4±0.7	<0.001	2.9±1.7	2.7±1.4	0.090	0.317
HDL-c, mmol/L	1.2±0.5	1.2±0.4	0.453	1.2±0.4	1.2±0.4	0.827	0.307
LDL-c, mmol/L	4.0±0.9	2.5±0.8	<0.001	3.9±0.8	3.8±0.7	0.175	0.656
ApoA-1, g/L	1.4±0.5	1.4±0.3	0.995	1.3±0.3	1.4±0.3	0.250	0.521
ApoB, g/L	1.1±0.3	1.0±0.3	0.001	1.1±0.2	1.0±0.2	0.097	0.112
ApoE, mg/L	57±28	47±25	<0.001	54±22	57±40	0.451	0.276
Lp-A, mg/L	204±192	202±209	0.884	193±179	199±190	0.840	0.631
UA, μmol/l	416±104	393±103	0.015	415±106	407±116	0.700	0.966
FFA, mmol/L	572±220	418±118	<0.001	543±177	509±162	0.264	0.353
FBG, mmol/L	5.6±1.2	5.4±1.0	0.006	5.5±1.3	5.3±1.2	0.213	0.453
FINS, μU/mL	12.1±9.6	11.3±8.6	0.328	11.5±6.0	11.5±7.9	0.956	0.552
HOMA-IR	3.1±3.2	3.0±2.8	0.655	2.8±1.7	2.8±1.9	0.813	0.336
HbA1c, %	6.1±1.1	5.9±1.1	0.735	6.1±1.2	5.8±1.1	0.219	0.981
FIB-4 index	1.27±0.95	1.23±0.80	0.756	1.25±0.77	1.19±0.67	0.643	0.904
NFS	−1.36±1.62	−1.70±2.03	0.366	−1.48±1.82	−2.12±2.35	0.325	0.728
LSM, kPa	6.5±2.4	6.4±2.3	0.700	6.1±1.6	6.6±2.0	0.239	0.277

Abbreviations: BMI, body mass index; WC, waist circumference; SBP, systolic blood pressure; DBP, diastolic blood pressure; T2DM, type 2 diabetes; ALT, alanine aminotransferease; AST, aspartate aminotransferase; GGT, gamma glutamyltranspeptidase; TC, total cholesterol; TG, triglyceride; HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol; ApoA-1, apolipoprotein A-1; ApoB, apolipoprotein B; ApoE, apolipoprotein E; LP-A, lipoprotein-A; UA, uric acid; FFA, free fatty acid; FBG, fasting blood glucose; FINS, fasting insulin; HOMA-IR, homeostatic model assessment of insulin resistance; HbA1c, glycated hemoglobin; FIB-4, Fibrosis-4; NFS, NAFLD fibrosis score; LSM, liver stiffness measurement.

Figure 1 Decrease trends of transaminases and blood lipids in the lipid-lowering group (n = 325) and control group (n = 216). Repeated-measures analysis of variance (ANOVA) for the comparison of effects on ALT (A), AST (B), GGT (C), total cholesterol (D), triglyceride (E), and LDL-c (F) between lipid-lowering group and control group. P values were for the ANOVA analysis between the two groups.

Abbreviations: ALT, alanine aminotransferease; AST, aspartate aminotransferase; GGT, gamma glutamyltranspeptidase; LDL-c, low-density lipoprotein cholesterol; TC, total cholesterol; TG, triglyceride.

Figure 2 Correlation analysis between changes in transaminase and blood lipids in the lipid-lowering group (n = 325) and control group (n = 216). ***P < 0.001, **P < 0.01. *P < 0.05.

Abbreviations: Δ, changes; ALT, alanine aminotransferease; AST, aspartate aminotransferase; GGT, gamma glutamyltranspeptidase; TC, total cholesterol; TG, triglyceride; LDL-c, low-density lipoprotein cholesterol; HDL-c, high-density lipoprotein cholesterol; ApoA-1, apolipoprotein A-1; ApoB, apolipoprotein B; ApoE, apolipoprotein E.

Figure 3 The impact of declining blood lipid levels on transaminase and GGT normalization. Comparison of transaminase and GGT normalization rate between the lipid-lowering group (n = 325) and control group (n = 216) (A), statin group (n = 216) and fibrate group (n = 91) (B and C), MAFLD with T₂DM group (n = 67) and without T₂DM group (n = 258), the male group (n = 241) and female group (n = 84) (C), and groups of 3 different reduction ranges in blood lipids (G). Comparison of LDL-c (D) and non-HDL-c (E) treated to target rate between the lipid-lowering group and the control group. Comparison of reduction ranges in blood lipids between the transaminase and GGT normalization group (n = 169) and nonnormalized group (n = 156) (F). ***P < 0.001, *P < 0.05.

Abbreviations: ALT, alanine aminotransferease; AST, aspartate aminotransferase; GGT, gamma glutamyltranspeptidase; TC, total cholesterol; TG, triglyceride; LDL-c, low-density lipoprotein cholesterol; HDL-c, high-density lipoprotein cholesterol; CVD, cardiovascular disease; T₂DM, type 2 diabetes.

Table 2 Univariate and Multivariate Analyses of Factors Associated with Transaminase and GGT Normalization by Lipid-Lowering Agents

Variables	Univariate		Multivariate
	OR (95% CI)	P-value	OR (95% CI)	P-value
Female	1.01 (0.55–1.85)	0.985	-	-
Age, years	1.01 (0.99–1.03)	0.479	-	-
Baseline BMI ≥23kg/m^2	0.74 (0.36–1.53)	0.419	-	-
Baseline TC ≥5.2mmol/L	1.26 (0.62–2.53)	0.523	-	-
Baseline TG ≥1.7mmol/L	1.25 (0.60–2.51)	0.525	-	-
Baseline LDL-c ≥3.4mmol/L	1.23 (0.64–2.36)	0.538	-	-
Weight loss (%)	1.81 (1.03–3.12)	0.039	1.60 (0.87–2.95)	0.132
TC decreased over 50%	1.84 (0.98–3.40)	0.049	1.28 (0.61–2.65)	0.514
TG decreased over 50%	2.08 (1.14–3.82)	0.018	2.07 (1.12–3.84)	0.020
LDL-c decreased over 50%	1.85 (1.03–3.32)	0.040	1.64 (0.83–3.21)	0.154

Abbreviations: GGT, gamma glutamyltranspeptidase; BMI, body mass index; TC, total cholesterol; TG, triglyceride; LDL-c, low-density lipoprotein cholesterol.