https://link.springer.com/book/10.1007%2F978-4-431-55790-6
The liver contains a wide array of immune cells such as macrophages, dendritic cells, and lymphocytes. In addition, nonimmune liver cells participate in the immune system by producing soluble pattern recognition receptors (PRRs) and complement proteins. This liver-mediated immune system maintains the local defense against microbial infection as well as systemic homeostasis. In fact, patients with advanced liver diseases have a high risk for infection due to impaired biosynthesis of secreted PRRs. Thus, the liver is to be considered as an immune organ.
The innate immune system can promptly eliminate nonspecific pathogens using several types of PRRs, including Toll-like receptors, NOD-like receptors, RIG-I-like receptors, and complement proteins. Representative products that act through PRR signaling are cytokines, which have antibacterial and antiviral effects. These mediators are used to kill pathogens with the assistance of other immune cells. Indeed, mice deficient in PRRs are susceptible to infection. However, an excessive immune response may lead to a sustained elevation of harmful cytokines. As a result, mice deficient in PRRs also show rather mild liver injuries, indicating that the lack of PRR signaling can provide beneficial effects. Thus, the innate immune system has dual functions in the prevention of infection as well as the development of liver diseases.
The gut microbiota plays a key role in the development of chronic inflammatory liver disease. The gut-liver axis involves inflammatory cells, cytokines, and other
molecules that cause liver deterioration. Dysbiosis is important in understanding
several liver diseases, especially in relation to the development of nonalcoholic fatty
liver disease, cirrhosis, and hepatocellular carcinoma. The aim of this report is to
provide a current overview of alterations in the gut microbiota associated with liver
diseases.
Liver is a main organ to regulate energy metabolism, nutrients production, storage and supply to the whole body. Glucose is the essential energy source for the whole body organs, especially for brain which has no ability to synthesize glucose and store glycogen or utilize non-glucose nutrients. Liver plays pivotal role to regulate glucose metabolism by precise regulation of glycogenolysis and gluconeogenesis, which are controlled not only by endocrine system, insulin and its counterregulatory hormones, but also by neuronal network, autonomic nervous system and brain. Recent development of molecular biology and gene analysis has revealed the precise molecular mechanism of hepatic carbohydrate metabolism and regulatory system by endocrine system, insulin or glucagon signaling pathway and those hormone-induced transcription of effector molecules, CREB, FoxO1, ChREBP, SREBPs, PGC1 or several kinds of enzymes. Recent studies also revealed that organ-to-organ network medicated autonomic neural system plays important roles in hepatic glucose metabolism.
Energy controlling system of carbohydrate metabolism by the liver and organ-to-organ network is excellent to starvation, however dose not adapt to the persistent satiety. Excessive energy intake causes hepatic dysregulation of glucose and lipid metabolism which promote insulin resistance, diabetes mellitus or non-alcoholic fatty liver disease.
The liver is the central organ for the metabolism of iron and copper. Therefore,
primary metabolic disorders of iron and copper give rise to liver diseases, and
secondary iron and copper disorders induced by chronic liver diseases potentially
modify or aggravate the clinical courses of the original liver diseases. This chapter
will review and discuss (1) iron and copper metabolism, (2) hemochromatosis and
Wilson disease as primary iron and copper metabolic disorders, and (3) mechanisms underlying secondary iron metabolic disorders induced by chronic liver diseases
such as chronic hepatitis C and nonalcoholic fatty liver disease (NAFLD). The degree of hepatic iron accumulation in chronic hepatitis C and NAFLD is not as severe as
that in hereditary hemochromatosis. However, mild to moderate hepatic iron
accumulation potentially modifies the disease progression and induces the
development of hepatocellular carcinoma (HCC) in chronic hepatitis C and NAFLD. Abnormal metabolism of copper in the liver is detected in patients with Wilson
disease. This is a peculiar disease, because it is a rare genetic metabolic disorder that can be treated by pharmacological treatments. However, prompt recognition,
diagnosis, and adequate treatment are essential, because inadequate management is fatal for the patients.