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Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most common chronic liver disease worldwide. Its development is multifactorial and involves genetic predisposition, metabolic dysfunction, lifestyle, environmental influences, and the gut microbiome (25).
Non-Alcoholic Fatty Liver Disease (NAFLD) / Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most common and increasing liver diseases worldwide, with a prevalence of 20–33%. NAFLD may progress to fibrosis, compensated cirrhosis, advanced cirrhosis, or hepatocellular carcinoma (24).
In 1980, the term non-alcoholic fatty liver disease (NAFLD) was introduced to describe fatty liver disease without other chronic liver diseases or alcohol consumption exceeding 140 grams per week for women and 210 grams per week for men. Because NAFLD is frequently associated with dysmetabolic comorbidities, it has recently been renamed metabolic dysfunction-associated fatty liver disease (MAFLD) (23).
NAFLD includes two pathologically distinct conditions: non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). The presence and extent of fibrosis on liver biopsy are the most relevant features for predicting liver-related mortality. NAFLD is the most common chronic liver disease in adults and children in the Western world. It is characterized by excessive hepatic fat accumulation associated with insulin resistance and is defined by steatosis in more than 5% of hepatocytes or a proton density fat fraction greater than 5.6% assessed by imaging (1).
Patients typically exhibit steatosis, hepatocellular ballooning, lobular polymorphonuclear cell infiltration and inflammation, fibrosis, lobular distortion, and cirrhosis (22).
NAFLD is a systemic disease that affects adipose tissue, pancreatic beta cells, and the cardiovascular system. It is the liver manifestation of metabolic syndrome and includes a spectrum ranging from liver steatosis, or NAFL, without inflammation to steatohepatitis, or NASH, fibrosis, cirrhosis, and eventual liver failure (2, 3, 4, 5, 6, 7, 8, 9).
NAFLD is the hepatic consequence of metabolic syndrome, which is associated with increased energy intake and reduced energy expenditure following lifestyle changes. It is also one of the earliest signs of metabolic syndrome and is associated with type 2 diabetes, insulin resistance, and dyslipidemia (11, 12, 13, 14, 15). NAFLD commonly occurs with obesity, diabetes, and high cholesterol or dyslipidemia (15).
Not all people with obesity develop NAFLD or NASH. NAFLD has also been reported in lean individuals, indicating that increased energy harvest alone is insufficient to induce NAFLD or NASH (16). Genetic predisposition, lifestyle, metabolic dysfunction, and environmental influences all contribute to disease development (25).
The gut–liver axis is a key communication pathway in MASLD. Changes in the composition and function of gut microbes may contribute to disease initiation and progression (25).
Microbiome disturbances may increase oxidative stress and impair mitochondrial function. Because mitochondria produce cellular energy, their dysfunction can aggravate metabolic disturbances and liver damage. Together, impaired gut barrier integrity, altered microbial metabolites, oxidative stress, and mitochondrial dysfunction provide important mechanistic links between the gut and MASLD (25).
NAFLD is a common and underdiagnosed comorbidity of many chronic diseases and is associated with altered gut bacterial communities (17). The gut microbiota is involved in the development of liver fat and fibrosis, and the association between the gut microbiota and liver is termed the gut–liver axis (20, 21).
Fatty liver can lead to fibrosis and is a risk factor for liver cancer, varicose veins, and sarcopenia. Liver fat and fibrosis are closely related to daily diet (18, 19).
End-stage liver disease (ESLD) or cirrhosis is a rare but often fatal complication of NAFLD. The crucial step in developing ESLD or cirrhosis is not triglyceride accumulation but hepatocyte damage (10).
Liver fat and fibrosis are closely related to daily dietary intake. The Mediterranean diet is known to help prevent the development and progression of NAFLD (18, 19).
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(17) Loman et al. 2018 Nutr Rev. 76(11):822–39
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see also:
Classic ketogenic diet (4:1) / Standard ketogenic diet (SKD)
Gut microbiota and NAFLD / MAFLD
Gut Microbiota–Liver Axis and Liver Fibrosis / Cirrhosis
Hepatic Disease and the Microbiota–Gut–Liver Axis
Leaky Gut Syndrome and Pro-inflammatory Cytokines
Liver Fibrosis / Cirrhosis