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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-02-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/11/2/468 |
| _version_ | 1827758394599014400 |
|---|---|
| author | Erica Vetrano Luca Rinaldi Andrea Mormone Chiara Giorgione Raffaele Galiero Alfredo Caturano Riccardo Nevola Raffaele Marfella Ferdinando Carlo Sasso |
| author_facet | Erica Vetrano Luca Rinaldi Andrea Mormone Chiara Giorgione Raffaele Galiero Alfredo Caturano Riccardo Nevola Raffaele Marfella Ferdinando Carlo Sasso |
| author_sort | Erica Vetrano |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T09:06:44Z |
| format | Article |
| id | doaj.art-2fcbda27755444e3bd022ac33869b973 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T09:06:44Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-2fcbda27755444e3bd022ac33869b9732023-11-16T19:18:41ZengMDPI AGBiomedicines2227-90592023-02-0111246810.3390/biomedicines11020468Non-alcoholic Fatty Liver Disease (NAFLD), Type 2 Diabetes, and Non-viral Hepatocarcinoma: Pathophysiological Mechanisms and New Therapeutic StrategiesErica Vetrano0Luca Rinaldi1Andrea Mormone2Chiara Giorgione3Raffaele Galiero4Alfredo Caturano5Riccardo Nevola6Raffaele Marfella7Ferdinando Carlo Sasso8Department of Advanced Medical and Surgical Sciences, Università della Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, Università della Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, Università della Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, Università della Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, Università della Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, Università della Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, Università della Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, Università della Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, Università della Campania “Luigi Vanvitelli”, 80138 Naples, ItalyIn 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.https://www.mdpi.com/2227-9059/11/2/468nonalcoholic fatty liver diseasetype 2 diabeteshepatocellular carcinoma |
| spellingShingle | Erica Vetrano Luca Rinaldi Andrea Mormone Chiara Giorgione Raffaele Galiero Alfredo Caturano Riccardo Nevola Raffaele Marfella Ferdinando Carlo Sasso Non-alcoholic Fatty Liver Disease (NAFLD), Type 2 Diabetes, and Non-viral Hepatocarcinoma: Pathophysiological Mechanisms and New Therapeutic Strategies Biomedicines nonalcoholic fatty liver disease type 2 diabetes hepatocellular carcinoma |
| title | Non-alcoholic Fatty Liver Disease (NAFLD), Type 2 Diabetes, and Non-viral Hepatocarcinoma: Pathophysiological Mechanisms and New Therapeutic Strategies |
| title_full | Non-alcoholic Fatty Liver Disease (NAFLD), Type 2 Diabetes, and Non-viral Hepatocarcinoma: Pathophysiological Mechanisms and New Therapeutic Strategies |
| title_fullStr | Non-alcoholic Fatty Liver Disease (NAFLD), Type 2 Diabetes, and Non-viral Hepatocarcinoma: Pathophysiological Mechanisms and New Therapeutic Strategies |
| title_full_unstemmed | Non-alcoholic Fatty Liver Disease (NAFLD), Type 2 Diabetes, and Non-viral Hepatocarcinoma: Pathophysiological Mechanisms and New Therapeutic Strategies |
| title_short | Non-alcoholic Fatty Liver Disease (NAFLD), Type 2 Diabetes, and Non-viral Hepatocarcinoma: Pathophysiological Mechanisms and New Therapeutic Strategies |
| title_sort | non alcoholic fatty liver disease nafld type 2 diabetes and non viral hepatocarcinoma pathophysiological mechanisms and new therapeutic strategies |
| topic | nonalcoholic fatty liver disease type 2 diabetes hepatocellular carcinoma |
| url | https://www.mdpi.com/2227-9059/11/2/468 |
| work_keys_str_mv | AT ericavetrano nonalcoholicfattyliverdiseasenafldtype2diabetesandnonviralhepatocarcinomapathophysiologicalmechanismsandnewtherapeuticstrategies AT lucarinaldi nonalcoholicfattyliverdiseasenafldtype2diabetesandnonviralhepatocarcinomapathophysiologicalmechanismsandnewtherapeuticstrategies AT andreamormone nonalcoholicfattyliverdiseasenafldtype2diabetesandnonviralhepatocarcinomapathophysiologicalmechanismsandnewtherapeuticstrategies AT chiaragiorgione nonalcoholicfattyliverdiseasenafldtype2diabetesandnonviralhepatocarcinomapathophysiologicalmechanismsandnewtherapeuticstrategies AT raffaelegaliero nonalcoholicfattyliverdiseasenafldtype2diabetesandnonviralhepatocarcinomapathophysiologicalmechanismsandnewtherapeuticstrategies AT alfredocaturano nonalcoholicfattyliverdiseasenafldtype2diabetesandnonviralhepatocarcinomapathophysiologicalmechanismsandnewtherapeuticstrategies AT riccardonevola nonalcoholicfattyliverdiseasenafldtype2diabetesandnonviralhepatocarcinomapathophysiologicalmechanismsandnewtherapeuticstrategies AT raffaelemarfella nonalcoholicfattyliverdiseasenafldtype2diabetesandnonviralhepatocarcinomapathophysiologicalmechanismsandnewtherapeuticstrategies AT ferdinandocarlosasso nonalcoholicfattyliverdiseasenafldtype2diabetesandnonviralhepatocarcinomapathophysiologicalmechanismsandnewtherapeuticstrategies |