Non-alcoholic Fatty Liver Disease (NAFLD), Type 2 Diabetes, and Non-viral Hepatocarcinoma: Pathophysiological Mechanisms and New Therapeutic Strategies

In recent years, the incidence of non-viral hepatocellular carcinoma (HCC) has increased dramatically, which is probably related to the increased prevalence of metabolic syndrome, together with obesity and type 2 diabetes mellitus (T2DM). Several epidemiological studies have established the associat...

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Published in:Biomedicines 2023-02, Vol.11 (2), p.468
Main Authors: Vetrano, Erica, Rinaldi, Luca, Mormone, Andrea, Giorgione, Chiara, Galiero, Raffaele, Caturano, Alfredo, Nevola, Riccardo, Marfella, Raffaele, Sasso, Ferdinando Carlo
Format: Article
Language:English
Subjects:
Alcoholism
Apoptosis
Cirrhosis
Diabetes
Diabetes mellitus (non-insulin dependent)
Epidemiology
Fatty acids
Fatty liver
Fibrosis
Hepatitis
Hepatocellular carcinoma
Hypertension
Immunomodulation
Inflammation
Insulin resistance
Insulin-like growth factor I
Insulin-like growth factors
Intestinal microflora
Iron
Lipids
Liver cancer
Liver cirrhosis
Liver diseases
Metabolic disorders
Metabolic syndrome
nonalcoholic fatty liver disease
Obesity
Oxidative stress
Pathogenesis
Physiological aspects
Review
Risk factors
type 2 diabetes
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Summary:In recent years, the incidence of non-viral hepatocellular carcinoma (HCC) has increased dramatically, which is probably related to the increased prevalence of metabolic syndrome, together with obesity and type 2 diabetes mellitus (T2DM). Several epidemiological studies have established the association between T2DM and the incidence of HCC and have demonstrated the role of diabetes mellitus as an independent risk factor for the development of HCC. The pathophysiological mechanisms underlying the development of Non-alcoholic fatty liver disease (NAFLD) and its progression to Non-alcoholic steatohepatitis (NASH) and cirrhosis are various and involve pro-inflammatory agents, oxidative stress, apoptosis, adipokines, JNK-1 activation, increased IGF-1 activity, immunomodulation, and alteration of the gut microbiota. Moreover, these mechanisms are thought to play a significant role in the development of NAFLD-related hepatocellular carcinoma. Early diagnosis and the timely correction of risk factors are essential to prevent the onset of liver fibrosis and HCC. The purpose of this review is to summarize the current evidence on the association among obesity, NASH/NAFLD, T2DM, and HCC, with an emphasis on clinical impact. In addition, we will examine the main mechanisms underlying this complex relationship, and the promising strategies that have recently emerged for these diseases' treatments.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines11020468