About the book
This book will deal with the basic concepts and immunopathological aspects of the pathogenesis of non-alcoholic fatty liver diseases (NAFLD), which is a global burden on human health. In particular, the relationship between NAFLD and systemic metabolic syndrome, which is highly likely to coexist, and the relationship between the intestinal microbiota and the immune environment is described. In addition, in a situation where there is no clear treatment yet, the status of treatment development in the clinical trial pipeline will be described.
A summary of its contents is as follows.
• As a consequence of the pandemic spread of obesity, NAFLD is one of the most important causes of liver disease worldwide in adults and children. The large volume of patients sets NAFLD apart from other liver diseases, meaning the major focus of clinical care is discerning those at the highest risk of progressive liver disease
• Because the overweighting in childhood and adolescence is associated with an increased risk of NAFLD later in life, the threshold of liver-related morbidity and/or mortality is reached at a younger age. Patients with NAFLD have a high risk of liver-related morbidity and mortality along with metabolic comorbidities and might place a growing strain on healthcare systems
• Whereas animal studies have demonstrated a potential causal role of gut microbiota in NAFLD, human studies have only just started to describe microbiome signatures in NAFLD.
• Proteobacteria are consistently enriched in steatosis and non-alcoholic steatohepatitis.
• Discrepant microbiome signatures across studies could be linked to the heterogeneity of geographical regions, ethnicity, population characteristics, microbiome sequencing tools, NAFLD diagnostic tools, disease spectrum, drug consumption, and circadian rhythm.
• The composition of the diet, in particular the types of lipids and carbohydrates, have an important role in the progression of NAFLD to NASH and fibrosis
• A complex interplay between the environment (especially diet), host genetics, and the gut microflora is crucial for the development and progression of NAFLD
• Activation of the innate immune system has an essential role in maintaining homeostasis and liver regeneration, as well as disease pathogenesis, acting in a cooperative rather than independent fashion
• Discoveries that characterized the importance of cell death in NAFLD progression triggered the development of novel therapeutic and diagnostic approaches for NAFLD
• Various types of cell death contribute to the development of NAFLD; extensive crosstalk and biochemical cooperation exists between these cell death pathways to drive disease progression
• Chronic hepatic inflammation represents the driving force in the evolution of nonalcoholic steatohepatitis (NASH) to liver fibrosis and/or cirrhosis.
• In both humans and rodents, NASH is characterized by B cell and T cell infiltration of the liver as well as by the presence of circulating antibodies targeting antigens originating from oxidative stress.
• Alterations in regulatory T cell and hepatic dendritic cell homeostasis have a role in triggering immune responses during the progression of NASH.
• While NAFLD progression to non-alcoholic steatohepatitis is becoming the leading cause of end-stage liver failure, the leading causes of death in patients with NAFLD are complications of cardiometabolic disease and a tight relationship exists between NAFLD, insulin resistance, and type II diabetes mellitus.
• A NAFLD has become the most common liver disease globally, yet there are currently no approved therapies and It is likely that developing therapeutics that target both NAFLD and cardiometabolic risk factors might be extremely beneficial.
