The lean phenotype in metabolic dysfunction-associated steatotic liver disease: diagnostic challenges and prognostic implications: Correspondence to editorial on “Normal-weight metabolic dysfunction-associated steatotic liver disease: reclassification, ch Sherlot Juan Song, Terry Cheuk-Fung Yip, Vincent Wai-Sun Wong, Dae Won Jun Clinical and Molecular Hepatology.2026; 32(3): e389. CrossRef
Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver conditions that are characterized by excess accumulation of fat in the liver, and is diagnosed after exclusion of significant alcohol intake and other causes of chronic liver disease. In the majority of cases, NAFLD is associated with overnutrition and obesity, although it may be also found in lean or non-obese individuals. It has been estimated that 19.2% of NAFLD patients are lean and 40.8% are non-obese. The proportion of patients with more severe liver disease and the incidence of all-cause mortality, liver-related mortality, and cardiovascular mortality among non-obese and obese NAFLD patients varies across studies and may be confounded by selection bias, underestimation of alcohol intake, and unaccounted weight changes over time. Genetic factors may have a greater effect towards the development of NAFLD in lean or non-obese individuals, but the effect may be less pronounced in the presence of strong environmental factors, such as poor dietary choices and a sedentary lifestyle, as body mass index increases in the obese state. Overall, non-invasive tests, such as the Fibrosis-4 index, NAFLD fibrosis score, and liver stiffness measurement, perform better in lean or non-obese patients compared to obese patients. Lifestyle intervention works in non-obese patients, and less amount of weight loss may be required to achieve similar results compared to obese patients. Pharmacological therapy in non-obese NAFLD patients may require special consideration and a different approach compared to obese patients.
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Fatty liver is now a major cause of liver disease in the Asia-Pacific region. Liver diseases in this region have distinctive characteristics. First, fatty liver is frequently observed in lean/normal-weight individuals. However, there is no standard definition of this unique phenotype. Second, fatty liver is often observed in patients with concomitant viral hepatitis. The exclusion of viral hepatitis from non-alcoholic fatty liver disease limits its value and detracts from the investigation and holistic management of coexisting fatty liver in patients with viral hepatitis. Third, fatty liver-associated hepatocellular carcinoma (HCC) is generally categorized as non-B non-C HCC. Fourth, the population is aging rapidly, and it is imperative to develop a practicable, low-intensity exercise program for elderly patients. Fifth, most patients and nonspecialized healthcare professionals still lack an awareness of the significance of fatty liver both in terms of intrahepatic and extrahepatic disease and cancer. Recently, an international expert panel proposed a new definition of fatty liver: metabolic dysfunction-associated fatty liver disease (MAFLD). One feature of MAFLD is that metabolic dysfunction is a prerequisite for diagnosis. Pertinent to regional issues, MAFLD also provides its diagnostic criteria in lean/normal-weight individuals. Furthermore, MAFLD is independent of any concomitant liver disease, including viral hepatitis. Therefore, MAFLD may be a more suitable definition for fatty liver in the Asia-Pacific region. In this review, we introduce the regional characteristics of fatty liver and discuss the advantages of MAFLD for improving clinical practice for liver disease in the region.
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