Page 28 - EJMO-9-3

Eurasian Journal of
Medicine and Oncology Role of common CXC chemokines in NAFLD

development of HCC. As a result, globally, NAFLD is beyond the superficial histopathologic similarities to
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rapidly escalating as the leading cause of liver-related deaths alcohol-induced liver disease, in 2020, a global group of
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and is becoming a critical factor for terminal liver disease, specialists formulated a more fitting terminology for the
primary liver cancer, and liver transplants. Although viral disease: metabolic dysfunction-associated fatty liver disease
hepatitis remains the major cause of death from chronic (MAFLD). In addition, the expert consensus emphasizes
liver disease, its deleterious effects are dwindling each year the important role of systemic metabolic dysregulation in
as the prevalence of hepatitis C virus declines worldwide; in driving liver disease and proposes a series of simple positive
contrast, NAFLD has evolved to become the primary cause criteria for the diagnosis and evaluation of MAFLD.
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of chronic liver disease and needs more attention from Diagnostically, however, the most significant difference
society. At present, invasive liver biopsy cytology is still the between NAFLD and MAFLD is not the dysregulation of
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“gold standard” for diagnosing NAFLD, but popularizing metabolic pathways, but rather whether or not concomitant
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this test in clinics is difficult, which leads to many patients liver disease is excluded. In summary, NAFLD tends to be an
being diagnosed with NAFLD at a more severe stage; in exclusionary diagnosis, whereas MAFLD is more focused
addition, since the pathophysiology of NAFLD is affected on telling us what the disease is. 14,15 This change has helped
by numerous metabolic, genetic, and microbiome factors, physicians to be able to recognize and treat all of the diseases
the underlying mechanisms of NAFLD remain largely of the liver in a holistic way in some patients. In comparison
unclear, leading to a scarcity of specific drugs to treat the to NAFLD, studies have found that the use of MAFLD
disease. 7 increases the identification of individuals with high-risk
The development of NAFLD can be described with features for progressive liver disease, and its relatively simple
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a multiple-hit model involving multiple stressors, and diagnosis facilitates awareness and understanding of the
although the underlying mechanisms of hepatocellular disease by clinicians other than hepatologists, facilitating
steatosis are well elucidated, the pathogenesis of NASH early management of the disease. 16,17 The term “non-
remains elusive. It is certain that during the development alcoholic” has been used for more than 40 years since it was
of NAFLD, disorders of lipid metabolism lead to the first coined in 1980, and the introduction of MAFLD has
production of lipotoxic lipids, which induce cellular stress had the effect of undermining public understanding of the
(including oxidative stress and endoplasmic reticulum two diseases; moreover, a proportion of patients who meet
stress), activation of inflammatory vesicles, and apoptotic the diagnostic criteria for NAFLD but have no metabolic
cell death, as well as subsequent inflammatory stimulation, risk factors have been identified as being at high risk for
tissue regeneration, and fibrosis, in which inflammatory and MAFLD. Most importantly, MAFLD has been proposed
pro-fibrotic macrophages are implicated in the progression for a relatively short period of time and its research data is
of liver fibrosis. Inflammatory factors are a major driving significantly less compared to NAFLD, so the main body
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force in the development of non-alcoholic steatohepatitis of the discussion in this article places a bigger focus on
and liver fibrosis, which in turn is a substantial predictor NAFLD.
of liver-related morbidity and mortality, thus, there is great While the early stages of NAFLD show only simple
clinical potential to reverse the progression of NASH by steatosis of the liver cells, the progressive stages of NASH
modulating inflammatory factors. The interplay between result in liver cell damage and inflammation, and the
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chemokines and their respective receptors is recognized histologic features of NASH are the presence of liver cell
as a crucial element in the evolution from simple steatosis ballooning and inflammation in the liver lobes in addition
to steatohepatitis, in which the CXC chemokine family- with liver steatosis. Overnutrition is a major driver of
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mediated inflammatory response is highly relevant in the NAFLD. Excessive intake of energy-dense substances
pathogenesis of NAFLD, and there exists a considerable such as fats and carbohydrates leads to dilation of adipose
research potential for the diagnosis and treatment of depots and accumulation of ectopic fat. In this context,
NAFLD. macrophage infiltration into visceral tissues creates a pro-
inflammatory state that further promotes insulin resistance.
2. Definitions and pathogenesis Insulin resistance promotes free fatty acid transport to
NAFLD is metabolic disease that is closely associated the liver, ultimately leading to dysregulation of lipid
with insulin resistance and genetic susceptibility. With metabolism and further development of lipotoxic lipids,
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the understanding of the disease and the need for clinical causing intracellular oxidative and endoplasmic reticulum
diagnosis, many clinicians and researchers find it difficult stress, inflammatory vesicle activation, and apoptotic cell
to meet the clinical, scientific, and patient needs of NAFLD death, resulting in hepatocellular injury and development
as a traditional generic term. To more accurately reflect the of hepatic inflammation. However, these pathways in
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pathogenesis of the disease and to expand the terminology NAFLD are influenced by numerous metabolic, genetic,

Volume 9 Issue 3 (2025) 20 doi: 10.36922/ejmo.8383