By analysing the health examination results of 795 participants using the new definition of MAFLD, the findings are as follows.
The prevalence of NAFLD was 43.40% and that of MAFLD was 44.78%. Compared with healthy individuals and NAFLD + MAFLD- patients, MAFLD patients had a worse metabolic profile. The MAFLD diagnostic criteria facilitated the identification of metabolic disorders in this subset of patients who had been excluded by the NAFLD criteria due to other concurrent diseases, emphasizing the risk of progressive liver fibrosis in this subset. This finding has important implications for this population.
Fatty liver was present in 46.41% (369/795) of the 795 individuals investigated in this study, and the prevalence of liver steatosis detected by abdominal B-ultrasound was high. Possible reasons were that the health examination centre recruited participants in this study who were mostly from the urban area of Shanghai and mostly city dwellers with relatively affluent family status. In this study, the blood sample examination findings of patients with ultrasound confirmed fatty liver disease were significantly different in comparison with healthy participants. The normal population without hepatic steatosis had a lower BMI, blood pressure, serum liver enzyme profile and neutrophil percentage. They also had lower glucose metabolism disorder, liver fibrosis score and healthier lipid profile. These findings are highly consistent with previous studies on NAFLD[7, 17].
With the increase of the prevalence of liver steatosis caused by various factors, NAFLD diagnostic criteria gradually become difficult to meet the needs of clinical work. NAFLD diagnosis was an exclusion criterion, and a diagnosis of NAFLD required exclusion of specific diseases such as alcohol abuse, autoimmune hepatitis, drug-induced liver disease and chronic viral hepatitis. During NAFLD diagnosis, a subset of patients is excluded based on the presence of excessive alcohol intake, some types of systemic diseases that may cause liver injury, or other chronic liver diseases. As the prevalence increases in the population, the complexity of its clinical application makes patient management difficult. As an inclusive disease, the diagnosis of MAFLD can coexist with other liver diseases or systemic diseases that lead to liver steatosis. In the clinic, MAFLD can be regarded as an independent systemic disease, and its diagnosis is directly based on metabolic abnormalities together with liver findings, efficiently facilitating the classification of patients with liver steatosis confirmed by various methods.
The harmful effects of hepatic steatosis in the human body are mainly reflected in two aspects: the risk of cardiovascular and cerebrovascular disease due to metabolic disorders and the adverse liver outcomes due to hepatic inflammation and liver fibrosis[3, 18].In this study, NAFLD- MAFLD + patients had statistically higher blood pressure, BMI, waist, NFS, and abnormal glucose metabolism (e.g., fasting glucose, fasting insulin, glycated haemohemoglobin, insulin resistance index). The NAFLD + MAFLD- and NAFLD- MAFLD + groups differed significantly based on their glucose metabolism profile, with the MAFLD + group exhibiting increased metabolic disorder and a possible trend towards cardiovascular and cerebrovascular disease; however, this study failed to find a significant difference due to the small sample size[5, 19].
The presence of metabolic disorders in this subset of patients is highly overlooked, and their risks of metabolic disorders, steatohepatitis, and advanced liver fibrosis are also difficult to appreciate, representing a blind area for diagnosis, monitoring, and treatment of NAFLD-related diseases. As a group of acquired metabolic stress-related disorders, most simple fatty livers are benign, whereas a subset of patients may develop NASH, which is at risks of progression to liver fibrosis and associated complications, including hepatocellular cancer[20]. Therefore, timely detection of NASH and progressive liver fibrosis is very important[21]. Previous studies showed that NAFLD patients with obesity and abnormal glucose metabolism were more likely to have adverse hepatic outcomes, whereas this study found that the NAFLD- MAFLD + group had a higher noninvasive liver fibrosis score NFS than the NAFLD + MAFLD- group. Previous studies have found that the new diagnostic criteria for MAFLD will be more helpful in identifying patients with advanced liver fibrosis than the NAFLD criteria[4, 14]. These results suggest that the MAFLD diagnostic criteria not only alert the population to a greater risk of CVD but also identify a group who may have adverse hepatic outcomes due to fatty liver progression[22, 23].
Other previous studies have shown that NAFLD patients with intercurrent diabetes have different liver disease outcomes than NAFLD patients without diabetes. The prevalence of NASH in NAFLD patients with diabetes was 68–78%, and the rate of progression to fibrosis was 22–60%[24]. Use of MAFLD diagnostic criteria with T2DM, at least 2 risk factors of metabolic disorder or overweight facilitates the identification of patients at high risk for liver disease[25].
A previous study compared the prevalence and incidence of MAFLD and previous NAFLD standards, evaluated the risk of fatty liver patients combined with other risk factors[26]. Another study found a group of NAFLD + MAFLD- patients who will not develop significant liver disease and lack other risk factors for liver injury due to low metabolic burden [27]. A prospective cohort study compared the all-cause mortality of MAFLD patients in different subgroups according to metabolic disorders[28]. However, the noninvasive liver injury evaluation indicators of adverse liver outcomes, such as NASH and advanced liver fibrosis, HOMA-IR calculated using fasting insulin, prediabetes assessed by glycosylated haemoglobin measurements, and important indicator C-reactive protein (CRP) were not totally available in these studies, making it difficult to accurately reflect the situation in patients. A meta-analysis showed that the new definition of MAFLD is helpful to identify a group of patients who may have serious liver injury[29]. This study verified this conclusion. Most of the studies included in the meta-analysis did not assess fasting insulin, CRP or other examination indicators in patients; thus, the situation of patients was not accurately reflected. On the other hand, the studies included in this meta-analysis came from different regions, and only some of them focused on Asian participants.
This study collected patients’ health examination data, including the history of hypertension, diabetes and other diseases as well as glycosylated haemoglobin, fasting insulin, CRP and other indicators, and this information very accurate for the diagnosis of MAFLD. On the other hand, this investigation has some limitations. The population with MAFLD had more severe metabolic abnormalities with a tendency to develop atherosclerosis. However, as the sample size of this group of NAFLD + MAFLD- patients was smaller, the difference only represented a trend, and no further significant results could be found. The relatively small number of samples in this study and the insufficient number of patients with fatty liver make it difficult to detect subtle differences between the two diagnostic criteria. In addition, the population recruited by the health examination centre included only the adult population and urban residents, and the relatively limited representation of this study may not reflect the most realistic and accurate disease prevalence in the whole population. Finally, in the general health examination results of the population investigated in this study, only abdominal B-ultrasound was used to evaluate the patients' liver lesions. If other techniques are applied, such as proton density fat fraction assessed by magnetic resonance imaging (MRI-PDFF), magnetic resonance spectroscopy (MRS), quantitative ultrasound techniques, biomarker tests for liver fibrosis, and liver biopsy, a more accurate and efficient assessment of liver injury in these patients will be possible in these patients[30, 31]. In the future, further large-scale research on the impact of new MAFLD diagnostic criteria will have important clinical significance.