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Metabolic-associated Fatty Liver Disease
Ming-Hua Zheng
Highlights
A panel of experts from 22 countries recently proposed a name change from nonalcoholic fatty liver disease (NAFLD) to metabolic-associated fatty liver disease, or MAFLD. Subsequently, new criteria for diagnosing MAFLD were provided to help guide clinicians in their clinical practice. The criteria are based on evidence of hepatic steatosis in the presence of one or more of overweight/obesity, type 2 diabetes, or metabolic dysregulation. The proposed novel diagnostic criteria represent a landmark in hepatology that combines our current understanding of obesity, metabolic syndrome and system biology into a single focus.
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PNPLA3 rs738409 C>G Variant Influences the Association Between Visceral Fat and Significant Fibrosis in Biopsy-proven Nonalcoholic Fatty Liver Disease
Gang Li, Liang-Jie Tang, Pei-Wu Zhu, Ou-Yang Huang, Rafael S. Rios, Kenneth I. Zheng, Sui-Dan Chen, Hong-Lei Ma, Giovanni Targher, Christopher D. Byrne, Xiao-Yan Pan, Ming-Hua Zheng
Highlights
Intra-abdominal visceral fat accumulation and patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 G/C gene polymorphism confer a greater susceptibility to nonalcoholic fatty liver disease (NAFLD). We examined whether the relationship between visceral fat accumulation and liver disease severity may be influenced by PNPLA3 rs738409 polymorphism.
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Redefinition of Fatty Liver Disease from NAFLD to MAFLD through the Lens of Drug Development and Regulatory Science
Yasser Fouad, Melissa Palmer, Minjun Chen, Arie Regev, Rajarshi Banerjee, Rob Myers, Robert Riccio, Richard Torstenson, Ramy Younes, Puneet S. Arora, Henrik Landgren, Morten A. Karsdal, Martin Blake, David A. Shapiro, Hans-Juergen Gruss, Muhammad Y. Sheikh, Dina Attia, Steven Bollipo, Alastair D. Smith, Bradley Freilich, Robert G. Gish, Detlef Schuppan
Highlights
Metabolic (dysfunction)-associated fatty liver disease (MAFLD) affects a third of the population and is a leading cause of liver-related death. Since no effective treatments exist, novel approaches to drug development are required. Unfortunately, outdated terminology and definitions of the disease are hampering efforts to develop new drugs and treatments. An international consensus panel has put forth an influential proposal for the disease to be renamed from nonalcoholic fatty liver disease (NAFLD) to MAFLD, including a proposal for how the disease should be diagnosed. As allies with the many stakeholders in MAFLD care―including patients, patients’ advocates, clinicians, researchers, nurse and allied health groups, regional societies, and others―we are aware of the negative consequences of the NAFLD term and definition. We share the sense of urgency for change and will act in new ways to achieve our goals. Although there is much work to be done to overcome clinical inertia and reverse worrisome recent trends, the MAFLD initiative provides a firm foundation to build on. It provides a roadmap for moving forward toward more efficient care and affordable, sustainable drug and device innovation in MAFLD care. We hope it will bring promising new opportunities for a brighter future for MAFLD care and improve care and outcomes for patients of one of the globe’s largest and costliest public health burdens. From this viewpoint, we have revisited this initiative through the perspectives of drug development and regulatory science.
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Metabolic-associated Fatty Liver Disease (MAFLD): A Multi-systemic Disease Beyond the Liver
Eda Kaya, Yusuf Yilmaz
Highlights
| • | An international panel of experts from 22 countries proposed a change in terminology and definition which reflects the pathogenesis of the disease more accurately from NAFLD to MAFLD;
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| • | NAFLD is a systemic disorder beyond the liver. Its extrahepatic involvements such as CKD, CVD, extrahepatic malignancy etc. have been studied before;
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| • | MAFLD and NAFLD seem to cover more or less the same patient population. However, the influence of the semantic change to “MAFLD” needs a reanalyzing of extrahepatic diseases in this newly defined group of patients. |
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Biomarkers of Metabolic (Dysfunction)-associated Fatty Liver Disease: An Update
Jawaher Alharthi, Mohammed Eslam
Highlights
The prevalence of metabolic (dysfunction)-associated fatty liver disease (MAFLD) is rapidly increasing and affects up to two billion individuals globally, and this has also resulted in increased risks for cirrhosis, hepatocellular carcinoma, and liver transplants. In addition, it has also been linked to extrahepatic consequences, such as cardiovascular disease, diabetes, and various types of cancers. However, only a small proportion of patients with MAFLD develop these complications. Therefore, the identification of high-risk patients is paramount. Liver fibrosis is the major determinant in developing these complications. Although, liver biopsy is still considered the gold standard for the assessment of patients with MAFLD. Because of its invasive nature, among many other limitations, the search for noninvasive biomarkers for MAFLD remains an area of intensive research. In this review, we provide an update on the current and future biomarkers of MAFLD, including a discussion of the associated genetics, epigenetics, microbiota, and metabolomics. We also touch on the next wave of multiomic-based biomarkers.
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Metabolic Dysfunction-associated Fatty Liver Disease (MAFLD) and Viral Hepatitis
Xiaolin Wang, Qing Xie
Highlights
| • | Patients with concomitant MAFLD and viral hepatitis are increasingly encountered in clinical practice;
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| • | wMost studies reveal a negative association between MAFLD and chronic HBV infection;
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| • | wGrowing evidence suggest the synergistic effect of MAFLD and CHB/CHC on liver disease progression;
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| • | wFurther clinical studies are required to provide evidence for the management of patients with coincidental MAFLD and viral hepatitis. |
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Epidemiology and Clinical Outcomes of Metabolic (Dysfunction)-associated Fatty Liver Disease
Huapeng Lin, Xinrong Zhang, Guanlin Li, Grace Lai-Hung Wong, Vincent Wai-Sun Wong
Highlights
| • | MAFLD not only is a new name but also involves a new definition;
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| • | MAFLD is the most common chronic liver disease with a global prevalence of 30%;
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| • | Genetic, lifestyle and environmental factors drive regional epidemiological differences;
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| • | Cardiovascular disease is the leading cause of death in MAFLD patients;
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| • | Liver complications are the leading cause of death in patients with F3-4 fibrosis. |
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Nonalcoholic Fatty Liver Disease (NAFLD) Name Change: Requiem or Reveille?
Shivaram P. Singh, Prajna Anirvan, Reshu Khandelwal, Sanjaya K. Satapathy
Highlights
| • | Lack of homogeneity and need for an inclusive definition are the reasons behind renaming NAFLD as MAFLD;
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| • | However, pathophysiology of NAFLD extends beyond Metabolic Syndrome;
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| • | Definition of MAFLD includes alcohol intake which would make it more heterogeneous;
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| • | This will create confusion among non hepatologists;
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| • | The word nonalcoholic goes a long way in destigmatising the patient. |
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Interaction of SAMM50-rs738491, PARVB-rs5764455 and PNPLA3-rs738409 Increases Susceptibility to Nonalcoholic Steatohepatitis
Ke Xu, Kenneth I. Zheng, Pei-Wu Zhu, Wen-Yue Liu, Hong-Lei Ma, Gang Li, Liang-Jie Tang, Rafael S. Rios, Giovanni Targher, Christopher D. Byrne, Xiao-Dong Wang, Yong-Ping Chen, Ming-Hua Zheng
Highlights
| • | Three SNPs independently associated with NASH in Chinese individuals;
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| • | Three SNPs synergistically increase susceptibility to NASH;
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| • | The synergistic effect elicits potent interactions among these three genes. |
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Pharmacological Therapeutics: Current Trends for Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)
Thaninee Prasoppokakorn, Panyavee Pitisuttithum, Sombat Treeprasertsuk
Highlights
| • | Many pharmacological therapies targeting different pathogenetic pathways for metabolic dysfunction-associated fatty liver disease (MAFLD), especially the term nonalcoholic steatohepatitis (NASH), are a focus of NASH resolution and fibrosis improvement in ongoing clinical trials. However, with redefinition of the disease, the terminology "NASH" has been abandoned;
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| • | The combination of different types of targeted pharmacotherapies is currently under investigation;
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| • | The comprising core drug or ultimate combination will need further studies and outcomes. We postulate that Farnesoid X receptor (FXR) agonists may be the fundamental drug for combination. |
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Alcohol and Metabolic-associated Fatty Liver Disease
Fu-Rong Sun, Bing-Yuan Wang
Highlights
| • | Metabolic dysfunction is common in drinking population;
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| • | MAC with low-risk lifestyle behaviors is related with decreased risk of MAFLD;
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| • | Heavy or binge drinking is related with insulin resistance and MAFLD. |
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Metabolic-associated Fatty Liver Disease as Assessed by the Fatty Liver Index Among Migrant and Non-migrant Ghanaian Populations
Anne-Marieke van Dijk, Sjoerd Dingerink, Felix Patience Chilunga, Karlijn Anna Catharina Meeks, Silver Bahendeka, Matthias Bernd Schulze, Ina Danquah, Tracy Bonsu Osei, Erik Serné, Charles Agyemang, Adriaan Georgius Holleboom
Highlights
| • | FLI as MAFLD proxy increased upon migration from rural Ghana to urban Europe;
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| • | The proportion of people with an elevated FLI significantly increased upon migration;
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| • | A strong independent association was found between type 2 diabetes mellitus and elevated FLI;
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| • | FLI was positively and independently associated with elevated 10-year asCVD risk. |
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Metabolic Disorders Combined with Noninvasive Tests to Screen Advanced Fibrosis in Nonalcoholic Fatty Liver Disease
Yi-Wen Shi, Fang-Ping He, Jin-Jun Chen, Hong Deng, Jun-Ping Shi, Cai-Yan Zhao, Yu-Qiang Mi, Zheng-Sheng Zou, Yong-Jian Zhou, Fu-Sheng Di, Rui-Dan Zheng, Qin Du, Jia Shang, Rui-Xu Yang, Branko Popovic, Bi-Hui Zhong, Jian-Gao Fan
Highlights
| • | lMetabolic disorders and even metabolic syndrome were frequent in NAFLD patients;
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| • | lReduced HDL-C and raised FPG were risk factors of advanced fibrosis;
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| • | lConsidering metabolic disorders could improve non-invasive diagnosis of fibrosis. |