1. Introduction
Metabolic disorders are one of the most important problems of modern society
[1]. Metabolic syndrome and related diseases are an important part of the epidemiology of chronic non-communicable diseases. Their prevalence is growing in many countries of the world, increasing the economic and social burdens
[2][3].
Non-alcoholic fatty liver disease (NAFLD) is closely associated with impaired metabolic processes and is considered one of the most common liver diseases in European countries. Its prevalence among the adult population varies depending on the method of diagnosis, age, sex, and some other characteristics and, according to various data, ranges from 17% to 46%
[4]. Such data roughly correspond to the occurrence of metabolic syndrome, which increases the risk of developing a severe form of the disease. NAFLD confidently demonstrates negative growth trends in parallel with the prevalence of obesity and type 2 diabetes, the key problems of modern society associated with impaired metabolism
[5]. It is assumed that the increase in the prevalence of NAFLD in the coming years will make it one of the leading causes of liver diseases, requiring its transplantation
[6][7][8][9]. It is important to note that NAFLD occurs not only in overweight and obese people, but also in 7% of people with normal body weight, often in young women with normal levels of liver enzymes
[10][11]. These data, as well as information about excessive health care costs associated with the disease, demonstrate the importance of NAFLD as a serious health problem worldwide
[12].
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of fat in the liver and is determined in the presence of steatosis in more than 5% of hepatocytes according to the results of histological examination or with a proton density of the fat fraction >5.6% according to proton magnetic resonance spectroscopy (PMRS) or fat–water MRI (magnetic resonance imaging). NAFLD includes two morphological forms with different prognosis: nonalcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). The severity of the disease in NASH is very variable, including fibrosis, the activity of which correlates with the stage of the disease, and cirrhosis. A liver biopsy should be performed to establish the final diagnosis of NAFLD.
The diagnosis of NAFLD involves the exclusion of secondary causes and significant alcohol consumption (more than 30 g per day for men and 20 g per day for women)
[13]. Alcohol consumption in doses exceeding those specified indicates alcoholic liver disease. It should be noted that a moderate amount of alcohol can also contribute to the development of NAFLD in patients with metabolic risk factors. At the same time, the overall effect of metabolic risk factors on the development of steatosis exceeds the effect of alcohol in these patients
[14].
Given the close and incompletely understood association of NAFLD with impaired metabolism, as well as the lack of understanding of all mechanisms of pathomorphological and clinical heterogeneity of the disease, another term, which is believed to better reflect current understanding of the pathogenesis of this disease, metabolically associated fatty liver disease (MAFLD), was proposed in 2020
[15][16]. The use of this term, as suggested by experts, will allow leveling out the influence of other liver diseases and alcohol intake in the diagnosis, while emphasizing the heterogeneity of all fatty liver diseases, and can also help in stratifying patients in order to choose the best treatment strategy
[16][17]. It should be noted that discussions regarding terminology continue, which once again underlines the complexity of the problem and the need for a better comprehensive analysis of it.
The relevance of the NAFLD problem is also due to the fact that patients may not seek medical care for a long time, and reliable tools required to confirm the diagnosis are not available to clinicians or are characterized by high cost and require qualified personnel, which is a serious problem for many countries of the world. Such conditions reduce the possibility of early diagnosis and prompt choice of an effective therapeutic intervention. In addition, NAFLD patients are more likely to have comorbidities that can present a much more severe clinical picture and are a major reason for seeking medical care. Among the most significant diseases that are associated with NAFLD are cardiovascular diseases
[17]. This relationship is well demonstrated by the commonality of key risk factors and some links of pathogenesis.
It is of interest to know that there is a higher prevalence of NAFLD among patients with chronic obstructive pulmonary disease (COPD). It was found that the frequency of steatosis, NASH, and fibrosis in COPD patients is 41.4%, 36.9%, and 61.3%, respectively
[18][19]. However, the data on the mechanisms of disease communication are incomplete and partially contradictory, which can be explained by the difficulties of diagnosis and variability of both NAFLD and the clinical heterogeneity of COPD. These connections are probably complex and include the involvement of impaired metabolic mechanisms, inflammation, and the resulting effects on organs and tissues of decreased pulmonary function and hypoxia (
Figure 1). It is shown that the severity of NAFLD is characterized by an independent association with a decrease in pulmonary function
[20]. At the same time, a greater decrease in forced expiratory volume in 1 s (FEV1) corresponds to a greater degree of liver steatosis
[21]. Patients with COPD and NAFLD with severe liver fibrosis showed a higher risk of cardiovascular events than in the general population of patients with liver fibrosis
[19].
Figure 1. The scheme of the relationship between NAFLD and COPD through metabolic disorders and inflammation.