Comparison of MAFLD and NAFLD Diagnostic Criteria in Real World

Su Lin; Jiaofeng Huang; Mingfang Wang; Rahul Kumar; Yuxiu Liu; Shiying Liu; Yinlian Wu; Xiaozhong Wang; Yueyong Zhu

Liver International. 2020;40(9):2082-2089.

Abstract and Introduction

Abstract

Background and Aims: Metabolic associated fatty liver disease (MAFLD) is a novel concept proposed in 2020, the utility of which has not been tested and validated in real world. We aimed to compare the characteristics of MAFLD and non-alcoholic fatty liver disease (NAFLD).

Methods: The data was retrieved from the third National Health and Nutrition Examination Surveys of the United States, which is an unbiased survey dataset and frequently used for the study of fatty liver disease.

Results: A total of 13 083 cases with completed ultrasonography and laboratory data were identified from the NHANES III database. MAFLD was diagnosed in 4087/13 083 (31.24%) participants, while NAFLD in 4347/13 083 (33.23%) amongst the overall population and 4347/12 045 (36.09%) in patients without alcohol intake and other liver diseases. Compared with NAFLD, MAFLD patients were significantly older, had higher BMI level, higher proportions of metabolic comorbidities (diabetes, hypertension) and higher HOMA-IR, lipid and liver enzymes. MAFLD patients with alcohol consumption were younger than those without, and more likely to be male. They had less metabolic disorder but higher liver enzymes. There were more cases with advance fibrosis in MAFLD patients with alcohol consumption.

Conclusion: MAFLD definition is more practical for identifying patients with fatty liver disease with high risk of disease progression.

Introduction

Fatty liver disease (FLD) is prevalent worldwide with the estimated prevalence of 25%.^[1] As a result of the insidious onset and prolonged course, the patient pool is continuously increasing.^[2] Based on the history of alcohol intake, it is currently artificially classified into two common forms: alcoholic liver disease (ALD) and non-alcoholic fatter liver disease (NAFLD).^[3] The definition however is far from perfect because of widespread use of mild to moderate amount of alcohol consumption in patients labelled as "NAFLD" and increasing prevalence of metabolic dysfunction in patients consuming harmful amount of alcohol and labelled as "ALD". Co-existence of mild-moderate alcohol consumption and metabolic derangements is fairly common in day-to-day clinical practice and its often challenging to classify patients into either of the two groups.^[4,5] Mis-reporting and under-reporting of alcohol consumption adds further complexity to the already complex definitions.

Metabolic associated fatty liver disease (MAFLD) is a novel concept proposed by an international consensus in 2020.^[6] MAFLD is significantly different from previous diagnostic criteria for NAFLD.^[7,8] The two most important and significant differences between MAFLD and NAFLD are, MAFLD diagnosis does not require exclusion of patients with alcohol intake, or other chronic liver diseases^[9] and the presence of metabolic abnormality is necessary for diagnosis of MAFLD.^[10]

As MAFLD criteria are recently developed based on consensus, utility of these criteria has not been tested and validated in real world. The difference in the characteristics of MAFLD and NAFLD has not been thoroughly explored. To address this specific question, we used a population-based data from National Health and Nutrition Examination Surveys (NHANES) to compare the differences between MAFLD and NAFLD criteria. The aim of this study is to characterize patients based on recently proposed MAFLD definition and compare the diagnostic ability of two definitions (NAFLD and MAFLD).

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Abstract and Introduction
Methods
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Discussion
References
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Table 1. Comparison of clinical parameters according to presence of MAFLD and NAFLD
Variables	Total	Non-MAFLD	MAFLD	P	Total	Non-NAFLD	NAFLD	P
N	13083	8996	4087		12045	7698	4347
Age (years)	43.65 ± 15.98	41.49 ± 15.86	48.39 ± 15.20	< 0.001	43.89 ± 16.08	42.24 ± 16.02	46.81 ± 15.77	< 0.001
Male (%)	6128 (46.84)	4092 (45.49)	2036 (49.82)	< 0.001	5393 (44.77)	3379 (43.89)	2014 (46.33)	0.010
BMI (Kg/m²)	27.29 ± 5.87	25.76 ± 4.98	30.68 ± 6.25	< 0.001	27.37 ± 5.9	26.17 ± 5.02	29.49 ± 6.69	< 0.001
DM (%)	1979 (15.13)	808 (8.98)	1171 (28.65)	< 0.001	1867 (15.50)	775 (10.07)	1092 (25.12)	< 0.001
Hypertension (%)	3255 (24.88)	1792 (19.92)	1463 (35.8)	< 0.001	2970 (24.66)	1627 (21.14)	1343 (30.89)	< 0.001
Platelets (×10⁹/L)	276.38 ± 70.98	275.51 ± 70	278.29 ± 73.05	0.042	276.34 ± 70.87	275.48 ± 69.78	277.87 ± 72.74	0.081
BUN (mmol/L)	4.90 ± 1.86	4.84 ± 1.85	5.04 ± 1.88	< 0.001	4.93 ± 1.88	4.90 ± 1.89	4.99 ± 1.87	0.010
Creatinine (μmolL)	94.15 ± 30.72	93.9 ± 30.97	94.7 ± 30.15	0.165	94.07 ± 31.49	94.04 ± 30.94	94.11 ± 32.44	0.917
TBIL(μmolL)	10.05 ± 5.64	10.03 ± 5.52	10.1 ± 5.9	0.572	9.98 ± 5.58	9.95 ± 5.46	10.02 ± 5.79	0.554
ALT (U/L)	18.81 ± 17.82	16.47 ± 14.83	23.96 ± 22.22	< 0.001	18.24 ± 16.49	15.94 ± 12.40	22.31 ± 21.34	< 0.001
AST (U/L)	22.59 ± 16.45	21.33 ± 14.85	25.35 ± 19.23	< 0.001	21.97 ± 15.08	20.58 ± 10.98	24.42 ± 20.18	< 0.001
GGT (U/L)	34.81 ± 53.11	29.84 ± 43.19	45.51 ± 68.66	< 0.001	32.25 ± 45.93	28.28 ± 37.96	39.06 ± 56.46	< 0.001
ALP (U/L)	86.05 ± 32.14	83.15 ± 31.65	92.42 ± 32.28	< 0.001	86.03 ± 32.57	83.46 ± 32.24	90.58 ± 32.68	< 0.001
LDH (U/L)	160.27 ± 38.79	156.8 ± 37.87	167.91 ± 39.69	< 0.001	160.34 ± 39.03	159.09 ± 37.96	162.55 ± 40.78	< 0.001
Total protein (g/L)	74.07 ± 4.68	73.96 ± 4.71	74.31 ± 4.62	< 0.001	73.99 ± 4.65	73.86 ± 4.65	74.22 ± 4.64	< 0.001
Albumin (g/L)	41.52 ± 3.83	41.67 ± 3.87	41.18 ± 3.73	< 0.001	41.45 ± 3.83	41.57 ± 3.88	41.24 ± 3.73	< 0.001
HbA1c (%)	5.53 ± 1.14	5.35 ± 0.89	5.91 ± 1.48	< 0.001	5.55 ± 1.16	5.39 ± 0.94	5.83 ± 1.44	< 0.001
HOMA-IR score	3.45 ± 8.82	3.38 ± 8.74	3.6 ± 8.98	0.201	3.67 ± 8.50	2.82 ± 7.36	5.18 ± 10.04	< 0.001
FPG (mmol/L)	5.63 ± 2.10	5.32 ± 1.49	6.3 ± 2.93	< 0.001	5.64 ± 2.15	5.37 ± 1.58	6.14 ± 2.82	< 0.001
TC (mmol/L)	5.28 ± 1.14	5.17 ± 1.10	5.53 ± 1.2	< 0.001	5.28 ± 1.15	5.21 ± 1.11	5.41 ± 1.20	< 0.001
TG (mmol/L)	1.63 ± 1.34	1.37 ± 0.97	2.19 ± 1.78	< 0.001	1.63 ± 1.29	1.4 ± 1.00	2.02 ± 1.61	< 0.001
LDL-C (mmol/L)	3.28 ± 0.99	3.23 ± 0.99	3.38 ± 1.00	< 0.001	3.29 ± 0.99	3.28 ± 0.99	3.30 ± 1.00	0.469
HDL-C (mmol/L)	1.32 ± 0.40	1.38 ± 0.40	1.19 ± 0.37	< 0.001	1.31 ± 0.39	1.35 ± 0.39	1.23 ± 0.38	< 0.001
APRI score	0.23 ± 0.32	0.21 ± 0.24	0.26 ± 0.44	< 0.001	0.22 ± 0.25	0.20 ± 0.18	0.25 ± 0.35	< 0.001
APRI score>1.5, n (%)	67 (0.51)	41 (0.46)	26 (0.64)	0.227	50 (0.42)	23 (0.30)	27 (0.63)	0.013
NFS score	-2.37 ± 1.52	-2.51 ± 1.51	-2.05 ± 1.51	< 0.001	-2.35 ± 1.52	-2.45 ± 1.51	-2.18 ± 1.52	< 0.001
NFS score >-1.455, n (%)	3275 (25.03)	1921 (21.35)	1354 (33.13)	< 0.001	3062 (25.42)	1743 (22.64)	1319 (30.34)	< 0.001
FIB4 score	0.96 ± 0.97	0.91 ± 0.73	1.06 ± 1.35	< 0.001	0.95 ± 0.75	0.91 ± 0.69	1.01 ± 0.84	< 0.001
FIB-4 score >1.3, n (%)	2545 (19.45)	1579 (17.55)	966 (23.63)	< 0.001	2314 (19.4)	1375 (18.04)	939 (21.82)	< 0.001
BARD score	2.36± 0.81	2.24± 0.71	2.64± 0.97	< 0.001	2.37± 0.81	2.29± 0.72	2.52± 0.93	< 0.001
BARD score>2, n (%)	5125 (39.17)	2678 (29.77)	2447 (59.87)	< 0.001	4820 (40.02)	2549 (33.11)	2271 (52.24)	< 0.001

Note: Categorical values are shown as n (%). Continuous variables are shown as mean ± standard deviation or median [interquartile range].
Abbreviations: FLD, Fatty liver disease; MAFLD, Metabolic associated fatty liver disease; NAFLD, nonalcoholic fatty liver disease; Non-MD-NAFLD, Non-metabolic dysfunction NAFLD; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; GGT, γ-glutamyl transpeptidase; ALP, alkaline phosphatase; HOMA-IR score, homeostasis model assessment-insulin resistance; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TG, triglyceride; TC, total cholesterol; BUN, blood urea nitrogen; HbA1c, glycated hemoglobin; FPG, fasting plasma glucose; UA, uric acid; DM, diabetes mellitus; APRI, AST-to-platelet ratio index; NFS, NAFLD fibrosis score; BARD score, body mass index, AST/ALT ratio, and diabetes score; FIB-4, Fibrosis-4 index.

Table 2. Comparison of clinical parameters according to presence of MAFLD, NAFLD and Non-MD-NAFLD group
Variables	NAFLD	MAFLD	Non-MD-NAFLD	P
Variables	NAFLD	MAFLD	Non-MD-NAFLD	NAFLD vs. MAFLD	NAFLD vs. Non-MD-NAFLD	MAFLD vs. Non-MD-NAFLD
N	4347	4087	620
Age (years)	46.81 ± 15.77	48.39 ± 15.20	35.13 ± 13.44	< 0.001	< 0.001	< 0.001
Male (%)	2014 (46.33)	2036 (49.82)	249 (40.16)	0.001	0.004	< 0.001
BMI(Kg/m²)	29.49 ± 6.69	30.68 ± 6.25	21.67 ± 2.08	< 0.001	< 0.001	< 0.001
DM (%)	1092 (25.12)	1171 (28.65)	0 (0)	< 0.001	< 0.001	< 0.001
Hypertension (%)	1343 (30.89)	1463 (35.8)	26 (4.19)	< 0.001	< 0.001	< 0.001
Platelets (×10⁹/L)	277.87 ± 72.74	278.29 ± 73.05	269.22 ± 67.74	0.790	0.003	0.002
BUN (mmolL)	4.99 ± 1.87	5.04 ± 1.88	4.49 ± 1.54	0.217	< 0.001	< 0.001
Creatinine (μmolL)	94.11 ± 32.44	94.7 ± 30.15	90.98 ± 39.19	0.385	0.059	0.024
TBIL (μmolL)	10.02 ± 5.79	10.1 ± 5.90	10.38 ± 6.35	0.537	0.182	0.299
ALT (U/L)	22.31 ± 21.34	23.96 ± 22.22	16.81 ± 17.84	< 0.001	< 0.001	< 0.001
AST (U/L)	24.42 ± 20.18	25.35 ± 19.23	23.53 ± 28.55	0.030	0.455	0.125
GGT (U/L)	39.06 ± 56.46	45.51 ± 68.66	27.69 ± 55.33	< 0.001	< 0.001	< 0.001
ALP (U/L)	90.58 ± 32.68	92.42 ± 32.28	78.01 ± 31.04	0.009	< 0.001	< 0.001
LDH (U/L)	162.55 ± 40.78	167.91 ± 39.69	152.24 ± 32.84	0.009	< 0.001	< 0.001
Total protein (g/L)	74.22 ± 4.64	74.31 ± 4.62	74.1 ± 4.81	0.349	0.551	0.293
Albumin (g/L)	41.24 ± 3.73	41.18 ± 3.73	42.06 ± 3.63	0.454	< 0.001	< 0.001
HbA1c (%)	5.83 ± 1.44	5.91 ± 1.48	5.08 ± 0.42	0.009	< 0.001	< 0.001
HOMA-IR score	5.18 ± 10.04	3.6 ± 8.98	2.57 ± 3.78	0.236	< 0.001	< 0.001
FPG (mmol/L)	6.14 ± 2.82	6.3 ± 2.93	4.92 ± 0.43	0.009	< 0.001	< 0.001
TC (mmol/L)	5.41 ± 1.20	5.53 ± 1.2	4.71 ± 0.96	< 0.001	< 0.001	< 0.001
TG (mmol/L)	2.02 ± 1.61	2.19 ± 1.78	1 ± 0.53	< 0.001	< 0.001	< 0.001
LDL-C (mmol/L)	3.3 ± 1	3.38 ± 1	2.77 ± 0.83	0.019	< 0.001	< 0.001
HDL-C (mmol/L)	1.23 ± 0.38	1.19 ± 0.37	1.55 ± 0.41	< 0.001	< 0.001	< 0.001
APRI score	0.25 ± 0.35	0.26 ± 0.44	0.26 ± 0.55	0.142	0.571	0.993
APRI score>1.5, n (%)	27 (0.62)	26 (0.64)	8 (1.90)	0.997	0.071	0.077
NFS score	-2.18 ± 1.52	-2.05 ± 1.51	-3 ± 1.32	< 0.001	< 0.001	< 0.001
NFS score >-1.455, n (%)	1319 (30.34)	1354 (33.13)	64 (10.32)	0.006	< 0.001	< 0.001
FIB4 score	1.01 ± 0.84	1.06 ± 1.35	0.87 ± 1.05	0.033	0.002	< 0.001
FIB-4 score >1.3, n (%)	939 (21.60)	966 (23.63)	75 (12.10)	0.027	< 0.001	< 0.001
BARD score	2.52± 0.93	2.64± 0.97	1.90± 0.43	< 0.001	< 0.001	< 0.001
BARD score>2, n (%)	2271 (52.24)	2447 (59.87)	0 (0)	< 0.001	< 0.001	< 0.001

Table 3. The comparison between MAFLD patients with or without alcohol intake
Variables	MAFLD without alcohol intake	MAFLD with alcohol intake	P
Variables	(n=3745)	(n = 342)	P
Age (years)	48.71 ± 15.28	44.9 ± 13.81	< 0.001
Male (%)	1777 (47.45)	259 (75.73)	< 0.001
BMI (Kg/m²)	30.79 ± 6.31	29.43 ± 5.48	< 0.001
DM (%)	1094 (29.21)	77 (22.51)	0.010
Hypertension (%)	1322 (35.3)	141 (41.23)	0.033
Platelets (×10⁹/L)	279.18 ± 73.48	268.48 ± 67.5	0.006
BUN (mmolL)	5.08 ± 1.91	4.69 ± 1.52	< 0.001
Creatinine (μmolL)	94.64 ± 31.1	95.38 ± 16.38	0.468
TBIL (μmolL)	9.98 ± 5.75	11.38 ± 7.24	< 0.001
ALT (U/L)	23.27 ± 21.76	31.54 ± 25.54	< 0.001
AST (U/L)	24.61 ± 18.48	33.42 ± 24.72	< 0.001
GGT (U/L)	41 ± 56.32	97.13 ± 139.89	< 0.001
ALP (U/L)	92.66 ± 32.44	89.87 ± 30.34	0.106
LDH (U/L)	167.93 ± 39.73	167.61 ± 39.34	0.885
Total protein (g/L)	74.24 ± 4.61	75.1 ± 4.6	0.001
Albumin (g/L)	41.1 ± 3.74	42.08 ± 3.59	< 0.001
HbA1c (%)	5.95 ± 1.51	5.5 ± 0.98	< 0.001
HOMA-IR score	3.53 ± 6.92	4.36 ± 20.97	0.466
FPG (mmol/L)	6.33 ± 2.99	5.95 ± 2.02	0.002
TC (mmol/L)	5.52 ± 1.2	5.6 ± 1.21	0.258
TG (mmol/L)	2.18 ± 1.67	2.32 ± 2.74	0.387
LDL-C (mmol/L)	3.39 ± 0.99	3.32 ± 1.03	0.446
HDL-C (mmol/L)	1.17 ± 0.35	1.35 ± 0.48	< 0.001
APRI score	0.25 ± 0.34	0.39 ± 1.02	0.009
APRI score>1.5, n (%)	20 (0.53)	6 (1.75)	0.017
NFS score	-2.04 ± 1.51	-2.18 ± 1.55	0.128
NFS score >-1.455, n (%)	1262 (33.70)	92 (26.90)	0.013
FIB4 score	1.03 ± 0.82	1.35 ± 3.8	0.129
FIB-4 score >1.3, n (%)	867 (23.15)	99 (28.95)	0.015
BARD score	2.66± 0.96	2.42± 1.06	< 0.001
BARD score>2, n (%)	2279 (60.85)	168 (49.12)	< 0.001

Note: Categorical values are shown as n (%). Continuous variables are shown as mean ± standard deviationor median [interquartile range].
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; GGT, γ-glutamyl transpeptidase; ALP, alkaline phosphatase; HOMA-IR score, homeostasis model assessment-insulin resistance; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TG, triglyceride; TC, total cholesterol; BUN, blood urea nitrogen; HbA1c, glycated hemoglobin; FPG, fasting plasma glucose; UA, uric acid; DM, diabetes mellitus; APRI, AST-to-platelet ratio index; NFS, NAFLD fibrosis score; BARD score, body mass index, AST/ALT ratio, and diabetes score; FIB-4, Fibrosis-4 index.

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Comparison of MAFLD and NAFLD Diagnostic Criteria in Real World

Abstract and Introduction

Abstract

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References

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