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.