In response to: Steatotic liver disease-know your enemies

Article information

Clin Mol Hepatol. 2024;30(2):284-286
Publication date (electronic) : 2024 February 19
doi : https://doi.org/10.3350/cmh.2024.0108
1Larner College of Medicine at the University of Vermont, Burlington, VT, USA
2Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
3Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, CA, USA
Corresponding author : Mindie H. Nguyen Division of Gastroenterology and Hepatology, Stanford University Medical Center, 780 Welch Road, Palo Alto, CA 94304, USA Tel: +1-650-498-6081, E-mail: mindiehn@stanford.edu
Editor: Mi Na Kim, Yonsei University College of Medicine, Korea
Received 2024 February 11; Accepted 2024 February 14.
Keywords: NAFLD; Epidemiology

Dear Editor,

We thank Dr. Mak for her review of our manuscript on the incidence of adverse outcomes associated with nonalcoholic fatty liver disease (NAFLD) which is now known as metabolic dysfunction associated steatotic liver disease (MASLD) [1,2]. As noted in the editorial, the new terminology of MASLD was selected to align with the co-morbidities most closely associated with this steatotic liver disease, in addition to recognizing the lack of alcohol use in certain cultures and in children. In addition to the change in terminology, the definition of MASLD was changed as well. Like NAFLD, MASLD requires steatosis to be present in ≥5% of hepatocytes and alcohol consumption to not be greater than 20 g for females and 30 g for males a day, in the absence of other liver disease associated with steatosis but in the presence of at least one cardiometabolic risk factor (CMR) [3]. As noted, the concordance between MASLD and NAFLD remains high even with the requirement for a CMR, which is promising given the vast amount of work that has already been completed to understand NAFLD and its’ burden [4,5].

Interestingly, these same studies noted that the presence of being overweight or obese is by far the most common CMR among those with MASLD, as well as being a significant and independent predictor for having MASLD. However, it must be noted that the cutoff for meeting the body mass index (BMI) CMR is ≥25 kg/m2 for non-Asians and ≥23.5 kg/m2 for Asians, which may miss those that are lean and have not yet developed other co-morbidities, especially those that are younger [3,4].

None the less, being overweight or obese appears to play a large role in defining MASLD and its prevalence, and with the rising rates of obesity among children and adults as well as the co-occurring increasing rates of type 2 diabetes (T2D), we can expect MASLD to continue to increase, especially in the younger population [5-9]. In fact, as highlighted in the editorial, we found that the age at which MASLD/NAFLD is being diagnosed is trending younger, which suggests that the adverse liver effects of obesity and T2D are already being seen in the increasing prevalence rates of NAFLD/MASLD. However, it is important to recognize that some of the increase in the number of cases could be due to the availability of non-invasive tests replacing the need for a liver biopsy. Despite this, the last forecasting model indicated that the prevalence of MASLD/NAFLD will be almost 60% by 2040 if nothing changes and that MASLD/NAFLD may no longer be considered just an older person’s disease [10].

With these facts in mind, along with the current incidence of adverse outcomes described in our study, the burden of MASLD/NAFLD may quickly become overwhelming for the healthcare system. Fortunately, as noted above, there are better non-invasive tests available for the diagnosis of MASLD/NAFLD and high-risk MASLD/NAFLD (those at risk for fibrosis stage 2 or higher), which have enabled the development of risk stratification algorithms to help clinicians institute appropriate interventions [11].

Although there are no direct pharmaceutical interventions yet for those with a more progressive disease, steatohepatitis (NASH/MASH), this position may soon change. In the meantime, diet and physical activity/exercise, which induce a weight loss of at least 5% to 10%, remain the cornerstones of treatment and have been better conceptualized to help clinicians intervene appropriately to assist in weight loss [12,13]. New T2D medications (Sodium-Glucose Transport Protein 2 [SGLT2] inhibitors and glucagon-like peptide-1 receptor agonists [GLP-1RAs]) are also showing promise in not only controlling diabetes but also assisting in weight loss and have been reported to improve cardiovascular health [14]. Bariatric surgery has also been shown to improve steatosis and maybe fibrosis if present and enough weight is lost [15]. However, most of these therapies, outside of diet and exercise, are approved for adults and not children. Therefore, work must also continue on developing community interventions with community and school policy makers to create a healthy environment in which children can not only learn but be physically active and provided healthy food on a consistent basis. A recent study that reviewed the availability of resources for a healthy community using six domains (policies, guidelines, civil awareness, epidemiology and data, NAFLD detection, and NAFLD care management) found no country was well prepared to address the burden of MASLD/NAFLD [16].

The lack of country preparedness is not surprising given that awareness of MASLD/NAFLD remains low [17]. Another purpose for the renaming of NAFLD to MASLD was to address what was thought to be a main driver of low awareness—patients and clinicians perceived stigma associated with the words “non-alcoholic” and “fatty”—whereby their presence hindered patient and healthcare provider communication. However, a recent survey among patients with NAFLD and healthcare providers of patients with NAFLD found a discrepancy between what patients perceived as stigmatizing and what healthcare providers perceived. In fact, only a very small percent of patients reported that the use of the terms “fatty’’ and “non-alcoholic” was stigmatizing compared to a majority of healthcare providers who thought these words caused discomfort and stigma among their patients [18]. As such, future research is needed to see if the name change will have helped to improve communication between patients and healthcare providers, with increased awareness as a result. Efforts must also continue to raise awareness of NAFLD/MASLD and its’ adverse outcomes, as outlined in our manuscript, among primary care physicians and endocrinologists where the majority of patients are seen.

Again, we thank Dr. Mak for her review, which brought attention to our work and allowed us the opportunity to expand the context of our work with the hope of bringing further awareness that MASLD/NAFLD is not a benign liver disease. As such, action is required among policymakers, healthcare providers, and the community to address this oncoming onslaught of liver disease, especially among the younger population.

Notes

Authors’ contribution

Michael H. Le: manuscript writing and editing. Linda Henry: manuscript writing and editing. Mindie H. Nguyen: manuscript writing and editing.

Conflicts of Interest

The authors have no conflicts to disclose.

Abbreviations

MASLD

metabolic dysfunction associated steatotic liver disease

NAFLD

non alcoholic fatty liver disease

MASH

metabolic dysfunction associated steatohepatitis

NASH

non alcoholic steatohepatitis

T2D

type 2 diabetes

SGLT2

Sodium-Glucose Transport Protein 2 Inhibitors

GLP

1Ras-glucagon-like peptide-1 receptor agonists

References

1. Mak LY. Steatotic Liver disease: Know your enemies. Clin Mol Hepatol 2024;30:171–173.
2. Le MH, Le DM, Baez TC, Dang H, Nguyen VH, Lee K, et al. Global incidence of adverse clinical events in non-alcoholic fatty liver disease: A systematic review and meta-analysis. Clin Mol Hepatol 2024;30:235–246.
3. Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol 2023;79:1542–1556.
4. Younossi ZM, Paik JM, Stepanova M, Ong J, Alqahtani S, Henry L. Clinical profiles and mortality rates are similar for metabolic dysfunction-associated steatotic liver disease and nonalcoholic fatty liver disease. J Hepatol 2024;Jan. 27. doi: 10.1016/j.jhep.2024.01.014.
5. Suzuki K, Tamaki N, Kurosaki M, Takahashi Y, Yamazaki Y, Uchihara N, et al. Concordance between metabolic dysfunction-associated steatotic liver disease and nonalcoholic fatty liver disease. Hepatol Res 2024. Jan. 17. doi: 10.1111/hepr.14011.
6. World Health Organization (WHO). Facts on obesity. World Obesity web site, <https://www.worldobesity.org/resources/resource-library/world-obesity-atlas-2023>. Accessed 21 Dec 2023.
7. Raygor V, Abbasi F, Lazzeroni LC, Kim S, Ingelsson E, Reaven GM, et al. Impact of race/ethnicity on insulin resistance and hypertriglyceridaemia. Diab Vasc Dis Res 2019;16:153–159.
8. Kodama K, Tojjar D, Yamada S, Toda K, Patel CJ, Butte AJ. Ethnic differences in the relationship between insulin sensitivity and insulin response: a systematic review and meta-analysis. Diabetes Care 2013;36:1789–1796.
9. Parcha V, Heindl B, Kalra R, Li P, Gower B, Arora G, et al. Insulin resistance and cardiometabolic risk profile among nondiabetic american young adults: Insights from NHANES. J Clin Endocrinol Metab 2022;107:e25–e37.
10. Le MH, Yeo YH, Zou B, Barnet S, Henry L, Cheung R, et al. Forecasted 2040 global prevalence of nonalcoholic fatty liver disease using hierarchical bayesian approach. Clin Mol Hepatol 2022;28:841–850.
11. Younossi Z, Alkhouri N, Cusi K, Isaacs S, Kanwal F, Noureddin M, et al. A practical use of noninvasive tests in clinical practice to identify high-risk patients with nonalcoholic steatohepatitis. Aliment Pharmacol Ther 2023;57:304–312.
12. Pouwels S, Sakran N, Graham Y, Leal A, Pintar T, Yang W, et al. Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss. BMC Endocr Disord 2022;22:63.
13. Younossi ZM, Zelber-Sagi S, Henry L, Gerber LH. Lifestyle interventions in nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 2023;20:708–722.
14. American Diabetes Association. Standards of care in diabetes—2023. Diabetes Care 2023;(Suppl 1)
15. Chauhan M, Singh K, Thuluvath PJ. Bariatric surgery in NAFLD. Dig Dis Sci 2022;67:408–422.
16. Lazarus JV, Mark HE, Villota-Rivas M, Palayew A, Carrieri P, Colombo M, et al. The global NAFLD policy review and preparedness index: Are countries ready to address this silent public health challenge? J Hepatol 2022;76:771–780.
17. Younossi ZM, Ong JP, Takahashi H, Yilmaz Y, Eguc Hi Y, El Kassas M, et al. A global survey of physicians knowledge about nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2022;20:e1456–e1468.
18. Younossi ZM, Alqahtani SA, Alswat K, Yilmaz Y, Keklikkiran C, Funuyet-Salas J, et al. Global survey of stigma among physicians and patients with nonalcoholic fatty liver disease. J Hepatol 2024;80:419–430.

Article information Continued