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Fibrotic Burden in Liver Differs Across Metabolic Dysfunction-Associated Fatty Liver Disease Subtypes

초록/요약

Background & Aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) is categorized into three subtypes: overweight/obese (OW), lean/normal weight with metabolic abnormalities, and diabetes mellitus (DM). We investigated whether fibrotic burden in liver differs across subtypes of MAFLD patients. Methods: This cross-sectional multicenter study was based on cohorts of patients who underwent a comprehensive medical health checkup between January 2014 and December 2020. A total of 42,652 patients with ultrasound-diagnosed fatty liver were included. Patients were classified as no MAFLD, OW-MAFLD, lean-MAFLD, and DM-MAFLD. Advanced liver fibrosis was defined based on the non-alcoholic fatty liver disease fibrosis score (NFS) or fibrosis-4 (FIB-4) index. Results: The mean age of the patients was 50.0 years, and 74.1% were male. The proportion of patients with NFS-defined advanced liver fibrosis was the highest in DM-MAFLD (6.6%), followed by OW-MAFLD (2.0%), lean-MAFLD (1.3%), and no MAFLD (0.2%). The proportion of patients with FIB-4-defined advanced liver fibrosis was the highest in DM-MAFLD (8.6%), followed by lean-MAFLD (3.9%), OW-MAFLD (3.0%), and no MAFLD (2.0%). With the “no MAFLD” group as reference, the adjusted odds ratios (95% confidence intervals) for NFS-defined advanced liver fibrosis were 4.46 (2.09–9.51), 2.81 (1.12–6.39), and 9.52 (4.46–20.36) in OW-MAFLD, lean-MAFLD, and DM-MAFLD, respectively, and the adjusted odds ratios for FIB-4-defined advanced liver fibrosis were 1.03 (0.78–1.36), 1.14 (0.82–1.57), and 1.97 (1.48–2.62) in OW-MAFLD, lean-MAFLD, and DM-MAFLD, respectively. Conclusions: Fibrotic burden in liver differs across MAFLD subtypes. Optimized surveillance strategies and therapeutic options might be needed for different MAFLD subtypes.

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초록/요약

배경 및 목적: 대사이상관련 지방간질환 (metabolic dysfunction-associated fatty liver disease, 이하 MAFLD)은 세개의 아형으로 분류된다: 과체중/비만 (overweight/obesity, 이하 OW), 대사이상을 동반한 정상체중 (이하 lean), 당뇨 (diabetes mellitus, 이하 DM). 우리는 MAFLD아형에 따라 간 섬유화의 정도가 다른 지 여부를 조사하였다. 방법: 이 횡단면 다기관 연구는 2014년 1월부터 2020년 12월 사이에 종합 건강 검진을 받은 코호트를 기반으로 하였다. 초음파로 진단된 지방간이 있는 총 42,652명의 환자가 본 연구에 포함되었다. 환자들은 no MAFLD, OW-MAFLD, lean-MAFLD, DM-MAFLD로 분류되었다. 진행된 간 섬유화는 non-alcoholic fatty liver disease fibrosis score (이하 NFS) 또는 fibrosis-4 (이하 FIB-4) index를 기반으로 정의하였다. 결과: 환자의 평균연령은 50.0세였고, 남자가 74.1%였다. NFS로 정의된 진행된 간 섬유화가 있는 환자의 비율은 DM-MAFLD (6.6%)에서 가장 높았고, OW-MAFLD (2.0%), lean-MALFD (1.3%), no MALFD (0.2%)가 그 뒤를 이었다. FIB-4로 정의된 진행된 간 섬유화가 있는 환자의 비율은 DM-MAFLD (8.6%)에서 가장 높았고, 그 다음이 lean-MAFLD (3.9%), OW-MAFLD (3.0%), no MAFLD (2.0%)의 순서였다. “no MAFLD”그룹을 참조로 하여 NFS로 정의된 진행된 간 섬유화에 대한 adjusted odds ratios (95% 신뢰구간)는 OW-MAFLD, lean-MAFLD, DM-MAFLD에서 각각 4.46 (2.09–9.51), 2.81 (1.12–6.39), 9.52 (4.46–20.36) 였고, FIB-4로 정의된 진행된 간 섬유화의 adjusted odds ratios (95% 신뢰구간)는 OW-MAFLD, lean-MAFLD, DM-MAFLS에서 각각 1.03 (0.78–1.36), 1.14 (0.82–1.57), and 1.97 (1.48–2.62)였다. 결론: 간 섬유화의 정도는 MAFLD의 아형에 따라 다르다. 따라서, 각각의 MAFLD 하위 유형에 따른 최적화된 감시 전략 및 치료 선택이 필요할 수 있다.

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목차

I. INTRODUCTION 1
II. METHODS 3
A. Study population 3
B. Definition of MAFLD 4
C. Assessment of fibrotic burden in liver 5
D. Definition of co-variates 6
E. Statistical analysis 7
III. RESULTS 8
A. Baseline characteristics 8
B. Comparison of participants with or without advanced liver fibrosis 10
C. Risk for advanced liver fibrosis according to the presence and subtypes of MAFLD 11
IV. DISCUSSION 20
V. CONCLUSION 24
VI. REFERENCE 25
VII. SUPPLEMENTARY APPENDIX 32
국문요약 37

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