Clin Mol Hepatol > Volume 27(2); 2021 > Article |
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NAFLD [6,7] | MAFLD [8] | |||
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For defining NAFLD, there must be | In adults with hepatic steatosis (detected either by imaging techniques, blood biomarkers/scores, or liver histology), these three groups are classified as MAFLD | |||
1) evidence of hepatic steatosis, either by imaging or histology (steatosis in >5% of hepatocytes), and | 1) Overweight/obesity (defined as BMI ≥25 kg/m2 in Caucasians or BMI ≥23 kg/m2 in Asians) | |||
2) lack of secondary causes of hepatic fat accumulation such as significant alcohol consumption (a daily alcohol consumption ≥30 g for men and ≥20 g for women), long-term use of a steatogenic medication, or monogenic hereditary disorders | 2) Lean/normal weight (defined as BMI <25 kg/m2 in Caucasians or BMI <23 kg/m2 in Asians) | |||
The presence of at least two of the following metabolic risk abnormalities: | ||||
• Waist circumference ≥102/88 cm in Caucasian men and women (or ≥90/80 cm in Asian men and women) | ||||
• Blood pressure ≥130/85 mmHg or specific drug treatment | ||||
• Plasma triglycerides ≥150 mg/dL (≥1.70 mmol/L) or specific drug treatment | ||||
• Plasma HDL-cholesterol <40 mg/dL (<1.0 mmol/L) for men and <50 mg/dL (<1.3 mmol/L) for women or specific drug treatment | ||||
• Prediabetes (i.e., fasting glucose levels 100 to 125 mg/dL [5.6 to 6.9 mmol/L], or 2-hour post-load glucose levels 140 to 199 mg/dL [7.8 to 11.0 mmol] or HbA1c 5.7% to 6.4% [39 to 47 mmol/mol]) | ||||
• Homeostasis model assessment of insulin resistance score ≥2.5 | ||||
• Plasma high-sensitivity C-reactive protein level >2 mg/L | ||||
3) Type 2 diabetes mellitus (according to widely accepted international criteria) |
Patients with cirrhosis in the absence of typical histology who meet at least one of the following criteria: | |
Past or present evidence of metabolic risk factors that meet the criteria to diagnose MAFLD, as described in the small box in Table 1, with at least one of the following: | |
1) Documentation of MAFLD on a previous liver biopsy* | |
2) Historical documentation of steatosis by hepatic imaging* |
Study | Number of patients | Clinical significance | |
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Zheng et al. [10] | Total/ NAFLD/MAFLD | 780/670/773 | 1. Clinical characteristics including metabolic profile, comorbid disease, and histology were not different between NAFLD and MAFLD groups. |
Both NAFLD and MAFLD | 663 | ||
Non-MR NAFLD | 7 | 2. Patients with dual etiology (MAFLD and alcohol) had higher gamma-glutamyl transferase levels and exhibited more severe hepatic steatosis compared to pure MAFLD group (single etiology). | |
MAFLD, but without NAFLD | 110 (A/66, V/40, I/4) | ||
Huang et al. [11] | Total/ NAFLD/MAFLD | 166/85/157 | 1. MAFLD, but without NAFLD group exhibited a significant increase in disease severity, as evaluated by both histology and laboratory findings, compared to those with non-MR NAFLD. |
Both NAFLD and MAFLD | 76 | ||
Non-MR NAFLD | 9 | 2. MAFLD criteria included an additional 38.9% of patients with hepatic steatosis, and it can help identify those with a high degree of disease severity for early intervention better than the previous NAFLD criteria. | |
MAFLD, but without NAFLD | 81 (A/5, V/46, M/23, I/7) | ||
Ciardullo and Perseghin [12] | Total/ NAFLD/MAFLD | 728/674/715 | 1. None of the 13 subjects with non-MR NAFLD presented with advanced liver fibrosis. However, those with MAFLD, but without NAFLD, showed similar advanced fibrosis to the overall estimate. The prevalence of advanced fibrosis among subjects with NAFLD and MAFLD was 7.5% and 7.4%, respectively. |
Both NAFLD and MAFLD | 661 | ||
Non-MR NAFLD | 13 | 2. The authors suggested that the recent change in diagnostic criteria did not affect the prevalence of the condition in the general USA population | |
MAFLD, but without NAFLD | 54 (NA) | ||
Lee et al. [16] | Total/ NAFLD/MAFLD | 3,628,540/2,680,217/3,573,644 | 1. A considerable proportion of middle-aged Korean adults have MAFLD, without satisfying the former definition of NAFLD. The change from NAFLD to MAFLD criteria may identify a greater number of individuals with metabolically complicated fatty liver and increased risk for CVD. |
Both NAFLD and MAFLD | 2,625,321 | ||
Non-MR NAFLD | 54,896 | 2. These studies might indicate that patients with non-MR NAFLD should be closely monitored, as they experience an increased risk for poor outcomes. | |
MAFLD, but without NAFLD | 948,323 (NA) | ||
Yamamura et al. [18] | Total/ NAFLD/MAFLD | 726/541/609 | 1. The MAFLD definition better identifies the group with fatty liver and significant fibrosis evaluated by non-invasive tests. Moreover, in patients with MAFLD, even mild alcohol consumption was associated with worsening of hepatic fibrosis measures. |
Both NAFLD and MAFLD | 424 | ||
Non-MR NAFLD | 117 | 2. It might be suggested that subjects with non-MR NAFLD might have no urgent diagnostic and therapeutic intervention needs due to a potentially favorable disease course. | |
MAFLD, but without NAFLD | 185 (NA) | ||
Lin et al. [22] | Total/ NAFLD/MAFLD | 13,083/4,347/4,087 | 1. MAFLD were significantly older and had higher BMI and higher proportions of metabolic comorbidities (T2DM, hypertension) compared to subjects with NAFLD. |
Both NAFLD and MAFLD | 3,727 | ||
Non-MR NAFLD | 620 | 2. Subjects with MAFLD and alcohol consumption were younger and had fewer metabolic disorders and a higher proportion of advanced fibrosis compared to those without. | |
MAFLD, but without NAFLD | 360 (NA) | ||
Wai-Sun Wong et al. [23] | Total/ NAFLD/MAFLD | 277/261/263 | 1. The prevalence of NAFLD and MAFLD was 25.7% and 25.9%, respectively, and the addition of the MAFLD criteria did not significantly change the prevalence of NAFLD. |
Both NAFLD and MAFLD | 247 | ||
Non-MR NAFLD | 14 | 2. However, the incidence of MAFLD was 25% lower than that of NAFLD. This difference was predominantly observed in subjects with a BMI of <23 kg/m2. This data suggests that the new MAFLD criteria may exclude patients with a more benign clinical course. | |
MAFLD, but without NAFLD | 16 (A/3, V/13) | ||
Niriella et al. [24] | Total/ NAFLD/MAFLD | 1028/940/990 | 1. Although NAFLD and MAFLD had similar metabolic traits at baseline and similar outcomes after 7-years, the MAFLD but without NAFLD group seemed to have higher risk of adverse outcomes compared to the non-MR NAFLD group. Although the increase in the index population was small, redefining NAFLD as MAFLD seemed to improve clinical utility. |
Both NAFLD and MAFLD | 902 | ||
Non-MR NAFLD | 38 | ||
MAFLD, but without NAFLD | 88 (NA) |
Outcome | Control (n*=255) | NAFLD (n*=708) |
NAFLD (vs. control) |
MAFLD (n*=735) |
MAFLD (vs. control) |
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Adjusted RR (95% CI) | P-value | Adjusted RR (95% CI) | P-value | ||||
Incident general obesity | 9/254 (3.5%) | 51/215 (24.6%) | 7.7 (3.8–15.4) | <0.001 | 57/213 (26.8%) | 8.3 (4.1–16.6) | <0.001 |
Incident central obesity | 39/246 (15.9%) | 37/109 (33.9%) | 2.6 (1.8–3.8) | <0.001 | 44/101 (43.6%) | 3.3 (2.3–4.7) | <0.001 |
Incident diabetes | 31/243 (12.8%) | 203/503 (40.4%) | 3.1 (2.2–4.4) | <0.001 | 216/523 (41.3%) | 3.2 (2.3–4.5) | <0.001 |
Incident hypertension | 36/218 (16.5%) | 109/232 (33.7%) | 2.1 (1.4–2.8) | <0.001 | 111/326 (34.0%) | 2.1 (1.5–2.9) | <0.001 |
Incident hypertriglyceridemia | 68/231 (29.4%) | 145/361 (40.2%) | 1.3 (1.1–1.7) | 0.026 | 153/372 (41.1%) | 1.4 (1.1–1.7) | 0.010 |
Incident hypo HDL cholesterolemia | 68/208 (32.7%) | 246/461 (53.4%) | 1.5 (1.2–1.7) | <0.001 | 250/487 (51.3%) | 1.5 (1.2–1.8) | <0.001 |
CVD non-fatal and fatal events | 4/253 (1.6%) | 36/665 (5.4%) | 3.7 (1.3–10.3) | 0.013 | 43/692 (6.2%) | 4.2 (1.5–11.5) | 0.006 |
Group | Event | Person-years | Rate* |
Hazard ratio (95% confidence interval) |
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Model 1 | Model 2 | Model 3 | ||||
No NAFLD | 108,283 | 63,604,662 | 170.2 | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
NAFLD | 74,140 | 23,921,515 | 309.9 | 1.82 (1.80–1.84) | 1.40 (1.38–1.41) | 1.41 (1.40–1.43) |
No MAFLD | 81,235 | 55,715,210 | 145.8 | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
MAFLD | 101,188 | 31,810,967 | 318.1 | 2.18 (2.16–2.20) | 1.56 (1.54–1.57) | 1.52 (1.51–1.54) |
Neither FLD | 79,987 | 55,203,158 | 144.9 | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
Non-MR NAFLD | 1,248 | 512,052 | 243.7 | 1.68 (1.59–1.78) | 1.20 (1.13–1.27) | 1.09 (1.03–1.15) |
MAFLD, but without NAFLD | 28,296 | 8,401,504 | 336.8 | 2.33 (2.30–2.36) | 1.55 (1.52–1.57) | 1.43 (1.41–1.45) |
Both FLD | 72,892 | 23,409,463 | 311.4 | 2.15 (2.13–2.17) | 1.57 (1.55–1.58) | 1.56 (1.54–1.58) |
Model 1 was unadjusted; model 2 was adjusted for age and sex; and model 3 was further adjusted for household income quartile, residential area, Charlson comorbidity index, tobacco use, exercise frequency, and estimated glomerular filtration rate.
NAFLD, nonalcoholic fatty liver disease; MAFLD, metabolic-associated fatty liver disease; MR, metabolic risk; FLD, fatty liver disease.
Seung Up Kim
https://orcid.org/0000-0002-9658-8050
Jin-Woo Lee
https://orcid.org/0000-0002-7227-4938
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