Correspondence on Letter regarding “Non-alcoholic fatty liver disease: Definition and subtypes”

Article information

Clin Mol Hepatol. 2023;29(3):817-819

Publication date (electronic) : 2023 May 17

doi : https://doi.org/10.3350/cmh.2023.0155

Seul Ki Han^1,2,3, Soon Koo Baik^1,2,3, Moon Young Kim^,1,2,3

¹Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea

²Regenerative Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea

³Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Korea

Corresponding author : Moon Young Kim Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju 26426, Korea Tel: +82-33-741-1229, Fax: +82-33-741-0951, E-mail: drkimmy@yonsei.ac.kr

Editor: Seung Up Kim, Yonsei University College of Medicine, Korea

Received 2023 April 25; Revised 2023 May 13; Accepted 2023 May 15.

Dear Editor,

We appreciate the constructive recommendation of Jeong et al. [1], which was a meaningful insight regarding fatty liver conceptualization. Fatty liver disease is characterized by fat accumulation resulting in hepatic inflammation, cirrhosis, and carcinoma. Currently, non-alcoholic fatty liver disease (NAFLD) is phenotypically considered a systemic metabolic syndrome. In metabolic syndrome, fatty liver is represented by one phenotype of a high-energy state, and various other complications resulting from this high-energy state can exist beyond the liver.

A recent review provided evidence that NAFLD is a risk factor for cerebrovascular disease (CVD) [2]. Kasper et al. [2] reported that NAFLD and CVD share a common pathophysiology, such as, PNPLA3, HSD 17B13, and PGC1a were related to genetic factors. Endothelial dysfunction, atherogenic dyslipidemia, systemic inflammation, coagulopathy, and altered gut microbiome are relevant factors. Moreover, NAFLD is reported as an independent risk factor for a CVD event, after adjusting other known risk factors. In some meta-analyses, outcomes were inconsistent; although, this may be due to the diversity in NAFLD definitions.

However, controversies regarding NAFLD as a risk factor for dementia are ongoing (Tables 1 and 2) [3-11]. In a recent study that included a large number of patients with NAFLD, the patients had a higher dementia rate, including vascular dementia [10]. This outcome is similar to that reported in a previous study [7]. However, primary care data from Germany have reported that NAFLD is not related to dementia occurrence [9]. Insulin resistance and hyperglycemia are known to cause dementia through glucose neurotoxicity and glycated end products [12]; however, they share some similarities with CVD. NAFLD is associated with arterial hypertension, atherosclerosis, coronary artery disease, and atrial fibrillation. Furthermore, NAFLD is often diagnosed at a young age and dementia at an old age; thus a limitation in revealing a direct relationship between the two diseases exists. Therefore, additional direct evidence is required. However, accumulating and updated data suggest that some mechanisms between NAFLD and brain dysfunction that result in dementia and Alzheimer’s disease are not fully investigated. This can be inferred from the fact that one author reported opposing results in 2 years.

Table 1.

Published papers suggesting the correlation between NAFLD and dementia

Table 2.

Published papers that do not suggest a correlation between NAFLD and dementia

Our review paper describes the simple, basic classification of NAFLD and its subtypes and summarizes the well-accepted contents for NAFLD. Relevance to other diseases and the latest concepts of prognosis are beyond the scope of our review. The productive opinion of Jeong et al. is also acceptable, and we hope that more evidence will be accumulated and new findings will be revealed throughout active investigations.