Gut Liver. 2022;16(3):433-442.

Metabolic Dysfunction-Associated Fatty Liver Disease Predicts Long-term Mortality and Cardiovascular Disease.

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제1저자 문준호, 김원, 구보경 · 교신저자 조남한

PMID 34635626 PMC9099391 DOI 10.5009/gnl210167 IF 4.1 소화기내과

소속 (5)

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea.
Divisions of Endocrinology and Metabolism, Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea.
Department of Preventive Medicine, Ajou University School of Medicine, Suwon, Korea.

Abstract

BACKGROUND/AIMS We investigated the effect of metabolic dysfunction-associated fatty liver disease (MAFLD) on future mortality and cardiovascular disease (CVD) using a prospective community-based cohort study.

METHODS Individuals from two community-based cohorts who were 40 to 70 years old were prospectively followed for 16 years. MAFLD was defined as a high fatty liver index (FLI ≥60) plus one of the following conditions: overweight/obesity (body mass index ≥23 kg/m²), type 2 diabetes mellitus, or ≥2 metabolic risk abnormalities. Nonalcoholic fatty liver disease (NAFLD) was defined as FLI ≥60 without any secondary cause of hepatic steatosis.

RESULTS Among 8,919 subjects (age 52.2±8.9 years, 47.7% of males), 1,509 (16.9%) had MAFLD. During the median follow-up of 15.7 years, MAFLD independently predicted overall mortality after adjustment for confounders (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.05 to 1.69) but NAFLD did not (HR, 1.20; 95% CI, 0.94 to 1.53). MAFLD also predicted CVD after adjustment for age, sex, and body mass index (HR, 1.35; 95% CI, 1.13 to 1.62), which lost its statistical significance by further adjustments. Stratified analysis indicated that metabolic dysfunction contributed to mortality (HR, 1.51; 95% CI, 1.21 to 1.89) and CVD (HR, 1.27; 95% CI, 1.02 to 1.59). Among metabolic dysfunctions used for defining MAFLD, type 2 diabetes mellitus in MAFLD increased the risk of both mortality (HR, 2.07; 95% CI, 1.52 to 2.81) and CVD (HR, 1.42; 95% CI, 1.09 to 1.85).

CONCLUSIONS MAFLD independently increased overall mortality. Heterogeneity in mortality and CVD risk of subjects with MAFLD may be determined by the accompanying metabolic dysfunctions.

Keywords

Cardiovascular diseaseMetabolic dysfunction-associated fatty liver diseaseMortalityNonalcoholic fatty liver disease

Figures

**Fig. 1** Overall and cause-specific mortality and CVD risk by MAFLD status. Cumulative survival rates according to (A) overall, (B) cancer-related, (C) liver-related, and (D) CVD-related mortality in subjects with (black line) and without (gray line) MAFLD for 16 years of follow-up were analyzed using Cox proportional hazards analysis (n=4,644; 729 [15.7%] were deceased; n=244 for cancer-related death; n=114 for CVD-related death; and n=41 for liver-related death). HRs (95% CIs) were calculated after adjustment for age, sex, body mass index, hypertension, dyslipidemia, smoking, diabetes mellitus, chronic kidney disease, high-sensitivity C-reactive protein, excess alcohol consumption, and a history of viral hepatitis (model 5 in Table 3). MAFLD, metabolic dysfunction-associated fatty liver disease; CVD, cardiovascular disease; HR, hazard ratio; CI, confidence interval.

**Fig. 2** Overall mortality and CVD events by MAFLD status. Cumulative survival rates for (A) for overall mortality or (B) incident CVD by the existence of either hepatic steatosis and/or metabolic dysfunction for 16 years of follow-up were analyzed using Cox proportional hazards analysis–(1) no hepatic steatosis and no metabolic dysfunction (n=1,739; normal control; dashed gray line), (2) no hepatic steatosis but metabolic dysfunction (n=5,659; solid gray line), (3) hepatic steatosis without metabolic dysfunction (n=12; dashed black line), and (4) hepatic steatosis with metabolic dysfunction (n=1,509; MAFLD; solid black line). No CVD events occurred in (3) hepatic steatosis without metabolic dysfunction. HRs (95% CIs) were calculated after adjustment for age, sex, body mass index, hypertension, dyslipidemia, smoking, diabetes mellitus, chronic kidney disease, high-sensitivity C-reactive protein, excess alcohol consumption, and a history of viral hepatitis. CVD, cardiovascular disease; MAFLD, metabolic dysfunction-associated fatty liver disease; HR, hazard ratio; CI, confidence interval.

그림 출처: PubMed Central 공개 논문 (PMC9099391)

Conflict of interest statement

CONFLICTS OF INTEREST . No potential conflict of interest relevant to this article was reported.

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