Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Current Concepts and Future Challenges

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Gastroenterology & Hepatopancreatobiliary Medicine".

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 13249

Special Issue Editors


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Guest Editor
1. Department of Medicine, Division of Gastroenterology and Hepatology, University of Arizona College of Medicine, Phoenix, AZ, USA
2. Department of Internal Medicine, Division of Gastroenterology and Hepatology, Banner University Medical Center, Phoenix, AZ, USA
Interests: nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; epidemiology; cirrhosis; liver transplantation; clinical research; meta-analysis

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Guest Editor
Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University, Stanford, CA, USA
Interests: nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; viral hepatitis; noninvasive panels; epidemiology; fibrosis; metabolic syndrome; clinical research; obesity; cirrhosis; hepatocellular carcinoma

Special Issue Information

Dear Colleagues,

Nonalcoholic fatty liver disease (NAFLD) is clinically defined as the presence of hepatic lipid accumulation that may progress to the more severe nonalcoholic steatohepatitis (NASH) with the development of cirrhosis, hepatocellular carcinoma, and need for liver transplantation. NAFLD is a multiorgan disease and has been strongly associated with type 2 diabetes mellitus, cardiovascular disease, chronic kidney disease, and extrahepatic malignancies. Interestingly, NAFLD can also be developed in individuals without overweight or obese or called “lean NAFLD or NAFLD in lean individuals”. More data for natural history and management of lean NAFLD are warranted to better understand this spectrum of NAFLD. Recently, a panel of international experts have proposed metabolic dysfunction-associated steatotic liver Disease (MASLD) instead of NAFLD. This proposed name change to MASLD has led to a hot debate in the field of NAFLD. This Special Issue will extensively cover key areas in NAFLD and MASLD research covering a wide spectrum that includes a population with normal body mass index or lean NAFLD/MASLD. The topic includes epidemiology, natural history, economic burden, risk factors, extrahepatic manifestation, current screening, and diagnostic methods, including noninvasive markers, lifestyle modification, current treatments, research gaps between NAFLD and MASLD, and future trajectories.

Dr. Karn Wijarnpreecha
Dr. Donghee Kim
Guest Editors

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Keywords

  • metabolic dysfunction-associated steatotic liver disease
  • nonalcoholic steatohepatitis
  • lean nonalcoholic fatty liver disease
  • epidemiology
  • screening and diagnostic method
  • artificial intelligence
  • noninvasive markers
  • treatment

Published Papers (8 papers)

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Research

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11 pages, 703 KiB  
Article
The Clinical Diagnosis-Based Nationwide Epidemiology of Metabolic Dysfunction-Associated Liver Disease in Korea
by Nam-Hun Lee, Seok-Ju Jeong, Jing-Hua Wang, Yu-Jin Choi, Hyeon-Muk Oh, Jung-Hyo Cho, Yo-Chan Ahn and Chang-Gue Son
J. Clin. Med. 2023, 12(24), 7634; https://doi.org/10.3390/jcm12247634 - 12 Dec 2023
Viewed by 843
Abstract
Background: Although most epidemiological studies have been conducted using a relatively small population or subjects who had medical screenings, the present study aimed to investigate the incidence and prevalence of MASLD (formerly NAFLD) in Korea using nationwide registry data provided by the Health [...] Read more.
Background: Although most epidemiological studies have been conducted using a relatively small population or subjects who had medical screenings, the present study aimed to investigate the incidence and prevalence of MASLD (formerly NAFLD) in Korea using nationwide registry data provided by the Health Insurance Review and Assessment Service (HIRA). Methods: Using nationwide medical records provided by HIRA, we analyzed the entire dataset of patients with MASL (KCD10-K76.0) and MASH (KCD10-K75.8) from 2010 to 2021 and calculated the incidence and prevalence by year, age, and gender. The prevalence and incidence rates were calculated by analyzing the HIRA data covering almost the entire population of Korea for 12 years, from 2010 to 2021, with an average population of 50,856,244 during this period. Statistical analyses included calculating confidence intervals using Ulm’s formula and conducting sex- and age-specific analyses with a Cochran–Armitage test for trends. Results: The annual incidence of MASL/MASH increased significantly from 9.71/0.37 in 2010 to 13.95/5.52 per 1000 persons in 2021 (p < 0.01). The annual prevalence of MASL increased from 15.69 in 2010 to 34.23 per 1000 persons in 2021, while the annual prevalence of MASH increased from 0.49 to 9.79 per 1000 persons between 2010 and 2021 (p < 0.01). Regarding the sex-dimorphic feature of MASLD, there was a male predominance in those < 50 years old but a female predominance in those ≥ 50 years old for the incidence and prevalence of MASL and the incidence of MASH. Conclusion: The incidence of MASL increased by 3% to 4% every year, while the incidence of MASH increased 14.91-fold from 2010 to 2021. The increasing trend is noteworthy compared with previous reports. Full article
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11 pages, 789 KiB  
Article
Clinical Predictive Score for Identifying Metabolic Dysfunction-Associated Steatotic Liver Disease in Individuals with Prediabetes Using Transient Elastography
by Nutthachoke Mahachai, Chaiwat Washirasaksiri, Pinyapat Ariyakunaphan, Chayanis Kositamongkol, Tullaya Sitasuwan, Rungsima Tinmanee, Chonticha Auesomwang, Naruemit Sayabovorn, Thanet Chaisathaphol, Pochamana Phisalprapa, Phunchai Charatcharoenwitthaya and Weerachai Srivanichakorn
J. Clin. Med. 2023, 12(24), 7617; https://doi.org/10.3390/jcm12247617 - 11 Dec 2023
Viewed by 675
Abstract
Scoring systems for metabolic dysfunction-associated steatotic liver disease (MASLD) in individuals with prediabetes have not been extensively explored. This study aimed to investigate the prevalence of MASLD and to develop predictive tools for its detection in high cardiometabolic people with prediabetes. A cross-sectional [...] Read more.
Scoring systems for metabolic dysfunction-associated steatotic liver disease (MASLD) in individuals with prediabetes have not been extensively explored. This study aimed to investigate the prevalence of MASLD and to develop predictive tools for its detection in high cardiometabolic people with prediabetes. A cross-sectional study was conducted using baseline data from the prediabetes cohort. All participants underwent transient elastography to assess liver stiffness. MASLD was defined using a controlled attenuation parameter value > 275 dB/m and/or a liver stiffness measurement ≥ 7.0 kPa. Cases with secondary causes of hepatic steatosis were excluded. Out of 400 participants, 375 were included. The observed prevalence of MASLD in individuals with prediabetes was 35.7%. The most effective predictive model included FPG ≥ 110 mg/dL; HbA1c ≥ 6.0%; sex-specific cutoffs for HDL; ALT ≥ 30 IU/L; and BMI levels. This model demonstrated good predictive performance with an AUC of 0.80 (95% CI 0.73–0.86). At a cutoff value of 4.5, the sensitivity was 70.7%, the specificity was 72.3%, the PPV was 58.8%, and the NPV was 81.5%. Our predictive model is practical, easy to use, and relies on common parameters. The scoring system should aid clinicians in determining when further investigations of MASLD are warranted among individuals with prediabetes, especially in settings with limited resources. Full article
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11 pages, 276 KiB  
Article
NAFLD Associates with Sarcopenia Defined by Muscle Mass and Slow Walking Speed: A Cross-Sectional Analysis from the Framingham Heart Study
by Sarah Altajar, Na Wang, Max P. Rosenthaler, Joanne M. Murabito and Michelle T. Long
J. Clin. Med. 2023, 12(24), 7523; https://doi.org/10.3390/jcm12247523 - 06 Dec 2023
Cited by 1 | Viewed by 740
Abstract
Sarcopenia is associated with NAFLD. It is unknown if the association is explained by shared risk factors. Our study sought to investigate the association between liver fat and sarcopenia in our cohort. Liver fat was measured on CT between 2008 and 2011. We [...] Read more.
Sarcopenia is associated with NAFLD. It is unknown if the association is explained by shared risk factors. Our study sought to investigate the association between liver fat and sarcopenia in our cohort. Liver fat was measured on CT between 2008 and 2011. We excluded heavy alcohol use and missing covariates. Muscle mass in a subset (n = 485) was measured by 24 h urinary creatinine. Physical function was defined by h strength and walking speed. Sarcopenia was defined as low muscle mass and/or low physical function. We created multivariable-adjusted regression models to evaluate cross-sectional associations between liver fat and low muscle mass, grip strength, and walking speed. The prevalence of hepatic steatosis was 30% (n = 1073; 58.1% women; mean age 65.8 ± 8.6 years). There was a significant positive association between liver fat and muscle mass in linear regression models. The association was not significant after adjusting for BMI. The odds of sarcopenia increased by 28% for each SD in liver fat (OR 1.28; 95% CI 1.02, 1.60) and persisted after accounting for confounders in multivariable-adjusted models (OR 1.30, 95% CI 1.02, 1.67). Further studies are needed to determine if there is a causal relationship between liver fat and sarcopenia and whether treatment of sarcopenia improves liver fat. Full article
14 pages, 1030 KiB  
Article
Aerobic and Muscle-Strengthening Physical Activity, Television Viewing, and Nonalcoholic Fatty Liver Disease: The CARDIA Study
by Daniel J. McDonough, Mahesh Mathew, Zachary C. Pope, Pamela J. Schreiner, David R. Jacobs, Jr., Lisa B. VanWagner, John Jeffrey Carr, James G. Terry, Kelley Pettee Gabriel, Jared P. Reis and Mark A. Pereira
J. Clin. Med. 2023, 12(17), 5603; https://doi.org/10.3390/jcm12175603 - 28 Aug 2023
Cited by 1 | Viewed by 1270
Abstract
Background: The prevalence of non-alcoholic fatty liver disease (NAFLD) in U.S. adults is over 30%, yet the role of lifestyle factors in the etiology of NAFLD remains understudied. We examined the associations of physical activity, by intensity and type, and television viewing with [...] Read more.
Background: The prevalence of non-alcoholic fatty liver disease (NAFLD) in U.S. adults is over 30%, yet the role of lifestyle factors in the etiology of NAFLD remains understudied. We examined the associations of physical activity, by intensity and type, and television viewing with prevalent NAFLD. Methods: Cross-sectional analysis of a population-based sample of 2726 Black (49%) and White (51%) adults (Mean (SD) age, 50 (3.6) years; 57.3% female) from the CARDIA study. Exposures were aerobic activity by intensity (moderate, vigorous; hours/week); activity type (aerobic, muscle-strengthening; hours/week); and television viewing (hours/week), examined concurrently in all models and assessed by validated questionnaires. Our outcome was NAFLD (liver attenuation < 51 Hounsfield Units), measured by non-contrast computed tomography, after exclusions for other causes of liver fat. Covariates were sex, age, race, study center, education, diet quality, smoking status, alcohol consumption, and body mass index or waist circumference. Results: 648 participants had NAFLD. In the fully adjusted modified Poisson regression model, the risk ratios per interquartile range of each exposure were moderate-intensity aerobic activity, 1.10 (95% CI, 0.97–1.26); vigorous-intensity aerobic activity, 0.72 (0.63–0.82); muscle-strengthening activity, 0.89 (0.80–1.01); and television viewing, 1.20 (1.10–1.32). Relative to less active participants with higher levels of television viewing, those who participated in ≥2 h/week of both vigorous-intensity aerobic and muscle-strengthening activity and <7 h/week of television viewing had 65% lower risk of NAFLD (risk ratio = 0.35, 95% CI = 0.23–0.51). Conclusion: Adults who follow public health recommendations for vigorous-aerobic and muscle-strengthening activity, as well as minimize television viewing, are considerably less likely to have NAFLD than those who do not follow the recommendations and who have relatively high levels of television viewing. Full article
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12 pages, 314 KiB  
Article
The Association between Personality Factors and Metabolic Parameters among Patients with Non-Alcoholic-Fatty Liver Disease and Type 2 Diabetes Mellitus—A Cross-Sectional Study
by Marcin Kosmalski, Rafał Frankowski, Monika Różycka-Kosmalska, Kasper Sipowicz, Tadeusz Pietras and Łukasz Mokros
J. Clin. Med. 2023, 12(13), 4468; https://doi.org/10.3390/jcm12134468 - 03 Jul 2023
Cited by 1 | Viewed by 1607
Abstract
Background: The increasing prevalence of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) states a serious problem for public health. The introduction of effective methods of treatment and prevention is crucial to avoid complications of these diseases. Among them, we [...] Read more.
Background: The increasing prevalence of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) states a serious problem for public health. The introduction of effective methods of treatment and prevention is crucial to avoid complications of these diseases. Among them, we can specify psychological factors that affect everyday life and determine the patient’s attitude towards therapy, and what follows, their compliance in treatment. The literature indicates these connections in various ways; in our study, we extend this view to include a broader perspective of human personality. Objective: We decided to investigate the associations between personality factors and metabolic parameters in patients with NAFLD and T2DM in order to better understand the patient’s approach to the treatment of a chronic disease, such as those mentioned, and to establish the basis for further research implementing psychological interventions in the treatment of NAFLD and T2DM. Methods: One hundred participants with NAFLD and T2DM underwent blood tests and anthropometric measures. Each of them was asked to complete five questionnaires evaluating their personality properties. Results: We revealed that a rise in body mass index is related to a fall in the emotional intelligence factor of utilizing emotions, and a rise in emotional perception. The decrease in task-oriented coping style and a rise in emotion-oriented coping style are associated with a waist-hip ratio increase. The increase in fasting plasma glucose is predicted by a decrease in task-oriented coping style score. A fall in social diversion coping style score is associated with a high-density lipoprotein increase; in turn, a triglycerides increase is connected with a decline in rhythmicity score. Conclusions: The personality factors are in relationship in the management of NAFLD and T2DM. They affect a patient’s approach to treatment, which is very important, because we know lifestyle and dietary interventions are an important part of the treatment of these diseases. The compliance manifests by lifestyle modifications, taking medications regularly, measuring blood glucose, and inspection visits in outpatients’ clinics are a large part of a diabetic’s life. Future studies introducing psychological intervention to improve, e.g., coping styles or rhythmicity are needed to implement new methods of patient management. Full article
13 pages, 254 KiB  
Article
Types of Physical Activity in Nonalcoholic Fatty Liver Disease and All-Cause and Cardiovascular Mortality
by Donghee Kim, Karn Wijarnpreecha, Brittany B. Dennis, George Cholankeril and Aijaz Ahmed
J. Clin. Med. 2023, 12(5), 1923; https://doi.org/10.3390/jcm12051923 - 28 Feb 2023
Cited by 3 | Viewed by 1495
Abstract
The impact of different types of physical activity (PA) on mortality in the context of nonalcoholic fatty liver disease (NAFLD) is not clearly defined and was investigated. This prospective study was performed using the 2007–2014 US National Health and Nutrition Examination Survey with [...] Read more.
The impact of different types of physical activity (PA) on mortality in the context of nonalcoholic fatty liver disease (NAFLD) is not clearly defined and was investigated. This prospective study was performed using the 2007–2014 US National Health and Nutrition Examination Survey with mortality follow-up through 2019. Over a median follow-up of 8.6 years, leisure-time and transportation-related PA that fulfilled the criteria outlined in the PA guidelines (≥150 min/week) in NAFLD were associated with a risk reduction in all-cause mortality (hazard ratio [HR]: 0.76, 95% confidence interval [CI]: 0.59–0.98 for leisure-time PA; HR: 0.62, 95% CI: 0.45–0.86 for transportation-related PA). Leisure-time and transportation-related PA in NAFLD were inversely associated with all-cause mortality in a dose-dependent manner (p for trends <0.01). Furthermore, the risk for cardiovascular mortality was lower in those meeting the PA guidelines for leisure-time PA (HR: 0.63, 95% CI: 0.44–0.91) and transportation-related PA (HR: 0.38, 95% CI: 0.23–0.65). Increasing sedentary behavior was linked to an increased risk of all-cause and cardiovascular mortality (p for trend <0.01). Meeting PA guidelines (≥150 min/week) for leisure-time and transportation-related PA has beneficial health effects on all-cause and cardiovascular mortality among individuals with NAFLD. Sedentary behavior in NAFLD showed harmful effects on all-cause and cardiovascular mortality. Full article
12 pages, 3043 KiB  
Article
DEXA Scan Body Fat Mass Distribution in Obese and Non-Obese Individuals and Risk of NAFLD—Analysis of 10,865 Individuals
by Caitlyn Tan, Kai En Chan, Cheng Han Ng, Michael Tseng, Nicholas Syn, Ansel Shao Pin Tang, Yip Han Chin, Wen Hui Lim, Darren Jun Hao Tan, Nicholas Chew, Elden Yen Hng Ong, Teng Kiat Koh, Jieling Xiao, Douglas Chee, Arun Valsan, Mohammad Shadab Siddiqui, Daniel Huang, Mazen Noureddin, Karn Wijarnpreecha and Mark D. Muthiah
J. Clin. Med. 2022, 11(20), 6205; https://doi.org/10.3390/jcm11206205 - 21 Oct 2022
Viewed by 2474
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide yet predicting non-obese NAFLD is challenging. Thus, this study investigates the potential of regional fat percentages obtained by dual-energy X-ray absorptiometry (DXA) in accurately assessing NAFLD risk. Using the United [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide yet predicting non-obese NAFLD is challenging. Thus, this study investigates the potential of regional fat percentages obtained by dual-energy X-ray absorptiometry (DXA) in accurately assessing NAFLD risk. Using the United States National Health and Nutrition Examination Survey (NHANES) 2011–2018, multivariate logistic regression and marginal analysis were conducted according to quartiles of regional fat percentages, stratified by gender. A total of 23,752 individuals were analysed. Males generally showed a larger increase in marginal probabilities of NAFLD development than females, except in head fat, which had the highest predictive probabilities of non-obese NAFLD in females (13.81%, 95%CI: 10.82–16.79) but the lowest in males (21.89%, 95%CI: 20.12–23.60). Increased percent of trunk fat was the strongest predictor of both non-obese (OR: 46.61, 95%CI: 33.55–64.76, p < 0.001) and obese NAFLD (OR: 2.93, 95%CI: 2.07–4.15, p < 0.001), whereas raised percent gynoid and leg fat were the weakest predictors. Ectopic fat deposits are increased in patients with non-obese NAFLD, with greater increases in truncal fat over gynoid fat. As increased fat deposits in all body regions can increase odds of NAFLD, therapeutic intervention to decrease ectopic fat, particularly truncal fat, may decrease NAFLD risk. Full article
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Review

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17 pages, 2227 KiB  
Review
Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Dysfunction-Associated Steatohepatitis: The Patient and Physician Perspective
by Wayne Eskridge, Donna R. Cryer, Jörn M. Schattenberg, Amalia Gastaldelli, Harmeet Malhi, Alina M. Allen, Mazen Noureddin and Arun J. Sanyal
J. Clin. Med. 2023, 12(19), 6216; https://doi.org/10.3390/jcm12196216 - 26 Sep 2023
Cited by 2 | Viewed by 3202
Abstract
Diagnosing and managing metabolic dysfunction-associated steatotic liver disease (MASLD) remains a major challenge in primary care due to lack of agreement on diagnostic tools, difficulty in identifying symptoms and determining their cause, absence of approved pharmacological treatments, and limited awareness of the disease. [...] Read more.
Diagnosing and managing metabolic dysfunction-associated steatotic liver disease (MASLD) remains a major challenge in primary care due to lack of agreement on diagnostic tools, difficulty in identifying symptoms and determining their cause, absence of approved pharmacological treatments, and limited awareness of the disease. However, prompt diagnosis and management are critical to preventing MASLD from progressing to more severe forms of liver disease. This highlights the need to raise awareness and improve understanding of MASLD among both patients and physicians. The patient perspective is invaluable to advancing our knowledge of this disease and how to manage it, as their perspectives have led to the growing recognition that patients experience subtle symptoms and that patient-reported outcomes should be incorporated into drug development. This review and expert opinion examine MASLD and metabolic dysfunction-associated steatohepatitis from the patient and physician perspective from pre-diagnosis to diagnosis and early care, through to progression to advanced liver damage. Specifically, the paper dives into the issues patients and physicians experience, and, in turn, what is required to improve diagnosis and management, including tips and tools to empower patients and physicians dealing with MASLD. Full article
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