Impact of cardiometabolic risk factors on hepatic fibrosis and clinical outcomes in MASLD: A population-based multi-cohort study

Background & Aims: Evaluating five cardiometabolic risk factors (CMRFs) is crucial for diagnosing metabolic dysfunction-associated steatotic liver disease (MASLD). This study investigated the impact of CMRFs on hepatic fibrosis and long-term clinical outcomes in patients with MASLD. Methods:...

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Main Authors: Huiyul Park, Terry Cheuk-Fung Yip, Eileen L. Yoon, Grace Lai-Hung Wong, Hye Sun Lee, Vincent Wai-Sun Wong, Jimmy Che-To Lai, Dae Won Jun
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:JHEP Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589555925000655
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author Huiyul Park
Terry Cheuk-Fung Yip
Eileen L. Yoon
Grace Lai-Hung Wong
Hye Sun Lee
Vincent Wai-Sun Wong
Jimmy Che-To Lai
Dae Won Jun
author_facet Huiyul Park
Terry Cheuk-Fung Yip
Eileen L. Yoon
Grace Lai-Hung Wong
Hye Sun Lee
Vincent Wai-Sun Wong
Jimmy Che-To Lai
Dae Won Jun
author_sort Huiyul Park
collection DOAJ
description Background & Aims: Evaluating five cardiometabolic risk factors (CMRFs) is crucial for diagnosing metabolic dysfunction-associated steatotic liver disease (MASLD). This study investigated the impact of CMRFs on hepatic fibrosis and long-term clinical outcomes in patients with MASLD. Methods: Two cross-sectional cohorts (Korean magnetic resonance elastography [n = 6,684] and US vibration-controlled transient elastography [n = 6,230]) were included to assess the impact of five CMRFs and their combinations on hepatic fibrosis. Two longitudinal cohorts (UK Biobank [n = 408,544; mean follow-up, 14.3 years] and Korea National Health Insurance data [n = 355,640; mean follow-up, 11.7 years]) were included to evaluate long-term outcomes, including liver-related events, hepatocellular carcinoma events, and overall, cardiovascular, and liver-related death. The risk of MASLD associated with CMRFs was assessed using logistic or Cox regression analysis, referencing participants without steatotic liver disease. Results: Across all four cohorts, patients with type 2 diabetes mellitus had the highest risk of hepatic fibrosis and long-term clinical outcomes. Among the five CMRFs, impaired fasting glucose (CMRF2) was the most significant risk factor for both hepatic fibrosis and long-term clinical outcomes. High blood pressure (CMRF3) was the second most significant risk factor for hepatic fibrosis, following CMRF2. Low high-density lipoprotein cholesterol level (CMRF5) exhibited comparable significance for long-term clinical outcomes. These clinical outcomes worsened with increasing severity of glucose abnormalities (normal and impaired fasting glucose levels and type 2 diabetes mellitus). Patients with MASLD and CMRF2 exhibited a two-to-four times higher risk of hepatic fibrosis and liver-related events compared with those without impaired fasting glucose levels, similar to MASLD accompanied by any four CMRFs. Conclusions: The impact of the five CMRFs on hepatic fibrosis and long-term clinical outcomes varied across different clinical outcomes and population characteristics. However, impaired fasting glucose (CMRF2) consistently demonstrated the highest risk. Impact and implications: Understanding the impact of the five cardiometabolic risk factors (CMRFs) used in the diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) on hepatic fibrosis and long-term clinical outcomes can improve the quality of care in the general population by facilitating the identification of at-risk individuals with MASLD. In our results, although the impact of each of the five CMRFs on hepatic fibrosis and long-term clinical outcomes varied depending on the type of clinical outcomes and the characteristics of the population, impaired fasting glucose (CMRF2) consistently showed the highest risk. Patients with MASLD and CMRF2 exhibited a two-to-four times higher risk of hepatic fibrosis and liver-related events compared with those without impaired fasting glucose levels, similar to MASLD accompanied by any four CMRFs. The utilization of impaired fasting glucose (CMRF2) can raise awareness among primary care providers regarding high-risk groups at the time of MASLD diagnosis.
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spelling doaj-art-5a069d466ae14e048fe30d08c970cf0b2025-08-20T03:10:24ZengElsevierJHEP Reports2589-55592025-06-017610138810.1016/j.jhepr.2025.101388Impact of cardiometabolic risk factors on hepatic fibrosis and clinical outcomes in MASLD: A population-based multi-cohort studyHuiyul Park0Terry Cheuk-Fung Yip1Eileen L. Yoon2Grace Lai-Hung Wong3Hye Sun Lee4Vincent Wai-Sun Wong5Jimmy Che-To Lai6Dae Won Jun7Department of Family Medicine, Myoungji Hospital, Hanyang University College of Medicine, Seoul, South KoreaDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China; Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, ChinaDepartment of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea; Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul, South KoreaDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China; Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, ChinaBiostatistics Collaboration Unit, Department of Research Affairs, Yonsei University College of Medicine, Seoul 03277, South KoreaDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China; Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, ChinaDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China; Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China; Corresponding author. Address: Department of Internal Medicine, Hanyang University College of Medicine, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, South Korea. Tel.: +82 2 2290 8338; Fax: +82 2 972 0068 (D.W. Jun); Department of Medicine and Therapeutics, 9/F Lui Che Woo Clinical Sciences Building, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong. Tel: +852-35053942; Fax: +852-26373852 (J.C-T. Lai).Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea; Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul, South Korea; Corresponding author. Address: Department of Internal Medicine, Hanyang University College of Medicine, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, South Korea. Tel.: +82 2 2290 8338; Fax: +82 2 972 0068 (D.W. Jun); Department of Medicine and Therapeutics, 9/F Lui Che Woo Clinical Sciences Building, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong. Tel: +852-35053942; Fax: +852-26373852 (J.C-T. Lai).Background & Aims: Evaluating five cardiometabolic risk factors (CMRFs) is crucial for diagnosing metabolic dysfunction-associated steatotic liver disease (MASLD). This study investigated the impact of CMRFs on hepatic fibrosis and long-term clinical outcomes in patients with MASLD. Methods: Two cross-sectional cohorts (Korean magnetic resonance elastography [n = 6,684] and US vibration-controlled transient elastography [n = 6,230]) were included to assess the impact of five CMRFs and their combinations on hepatic fibrosis. Two longitudinal cohorts (UK Biobank [n = 408,544; mean follow-up, 14.3 years] and Korea National Health Insurance data [n = 355,640; mean follow-up, 11.7 years]) were included to evaluate long-term outcomes, including liver-related events, hepatocellular carcinoma events, and overall, cardiovascular, and liver-related death. The risk of MASLD associated with CMRFs was assessed using logistic or Cox regression analysis, referencing participants without steatotic liver disease. Results: Across all four cohorts, patients with type 2 diabetes mellitus had the highest risk of hepatic fibrosis and long-term clinical outcomes. Among the five CMRFs, impaired fasting glucose (CMRF2) was the most significant risk factor for both hepatic fibrosis and long-term clinical outcomes. High blood pressure (CMRF3) was the second most significant risk factor for hepatic fibrosis, following CMRF2. Low high-density lipoprotein cholesterol level (CMRF5) exhibited comparable significance for long-term clinical outcomes. These clinical outcomes worsened with increasing severity of glucose abnormalities (normal and impaired fasting glucose levels and type 2 diabetes mellitus). Patients with MASLD and CMRF2 exhibited a two-to-four times higher risk of hepatic fibrosis and liver-related events compared with those without impaired fasting glucose levels, similar to MASLD accompanied by any four CMRFs. Conclusions: The impact of the five CMRFs on hepatic fibrosis and long-term clinical outcomes varied across different clinical outcomes and population characteristics. However, impaired fasting glucose (CMRF2) consistently demonstrated the highest risk. Impact and implications: Understanding the impact of the five cardiometabolic risk factors (CMRFs) used in the diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) on hepatic fibrosis and long-term clinical outcomes can improve the quality of care in the general population by facilitating the identification of at-risk individuals with MASLD. In our results, although the impact of each of the five CMRFs on hepatic fibrosis and long-term clinical outcomes varied depending on the type of clinical outcomes and the characteristics of the population, impaired fasting glucose (CMRF2) consistently showed the highest risk. Patients with MASLD and CMRF2 exhibited a two-to-four times higher risk of hepatic fibrosis and liver-related events compared with those without impaired fasting glucose levels, similar to MASLD accompanied by any four CMRFs. The utilization of impaired fasting glucose (CMRF2) can raise awareness among primary care providers regarding high-risk groups at the time of MASLD diagnosis.http://www.sciencedirect.com/science/article/pii/S2589555925000655cardiometabolic risk factorsMASLDcardiovascular mortalitygeneral populationliver-related deathhepatic fibrosis
spellingShingle Huiyul Park
Terry Cheuk-Fung Yip
Eileen L. Yoon
Grace Lai-Hung Wong
Hye Sun Lee
Vincent Wai-Sun Wong
Jimmy Che-To Lai
Dae Won Jun
Impact of cardiometabolic risk factors on hepatic fibrosis and clinical outcomes in MASLD: A population-based multi-cohort study
JHEP Reports
cardiometabolic risk factors
MASLD
cardiovascular mortality
general population
liver-related death
hepatic fibrosis
title Impact of cardiometabolic risk factors on hepatic fibrosis and clinical outcomes in MASLD: A population-based multi-cohort study
title_full Impact of cardiometabolic risk factors on hepatic fibrosis and clinical outcomes in MASLD: A population-based multi-cohort study
title_fullStr Impact of cardiometabolic risk factors on hepatic fibrosis and clinical outcomes in MASLD: A population-based multi-cohort study
title_full_unstemmed Impact of cardiometabolic risk factors on hepatic fibrosis and clinical outcomes in MASLD: A population-based multi-cohort study
title_short Impact of cardiometabolic risk factors on hepatic fibrosis and clinical outcomes in MASLD: A population-based multi-cohort study
title_sort impact of cardiometabolic risk factors on hepatic fibrosis and clinical outcomes in masld a population based multi cohort study
topic cardiometabolic risk factors
MASLD
cardiovascular mortality
general population
liver-related death
hepatic fibrosis
url http://www.sciencedirect.com/science/article/pii/S2589555925000655
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