Classic Autoimmune Liver Disorders and Celiac Hepatitis

Abstract

In addition to functioning in metabolism and detoxification, the liver also plays a key role in many essential immune-related tasks. Liver parenchyma hosts cellular elements of both innate and adaptive immune systems. The liver immune system repeatedly encounters foreign molecules belonging to microbes, environmental toxins, and food, which requires constant immune modulation in this complex microenvironment. 1 Therefore, it is no surprise that the liver can become a target of classic autoimmune disorders, such as autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and celiac disease (CD)-related liver injury, termed celiac hepatitis (CH). PaTHOGenesisDespite extensive research, the exact pathogenesis of autoimmune liver diseases remains uncertain (Table 1) 2-6 ; however, a common underlying hypothesis appears to be inflammation induced by a loss of tolerance to self-antigens in a genetically predisposed individual (Fig. 1). Aberrant and hyperactive immune response preferentially damages hepatocytes in AIH and cholangiocytes in PBC and PSC. Theoretically, foreign antigens resulting from common infections or xenobiotics may share structural similarities to hepatocyte or cholangiocyte self-antigens, triggering an autoimmune response, a mechanism termed molecular mimicry. 2 Cell-mediated autoimmunity is evident in both AIH and PBC by the presence of self-antigen-specific T cells within the liver. Specific targets of cellular or humoral autoimmunity in PSC are not clear yet. 2,7 Quantity and immunosuppressive capacity of regulatory T cells (Tregs) are altered in AIH, PBC, and PSC. 2,8,9 Sixty to eighty percent of patients with PSC have inflammatory bowel disease (IBD), and thus PSC may share underlying autoimmunity predisposition with IBD.

Delivery Strategy to Enhance the Therapeutic Efficacy of Liver Fibrosis via Nanoparticle Drug Delivery Systems

“…2,3 Liver fibrosis (LF) is considered to be a protective response to injury and is a common pathological feature of most chronic liver diseases. 4,5 The causes of LF are broad including chronic viral hepatitis B and C, 6 autoimmune and biliary diseases, 7 alcoholic steatohepatitis and nonalcoholic steatohepatitis (NASH), 8−11 and so on. The formation of LF is related to the activation of hepatic stellate cells (HSCs) and the secretion of an excessively deposited extracellular matrix (ECM).…”

“…Over the past few decades, chronic liver disease has created a significant social burden worldwide, and more than 2 million people have died of it according to the Global Burden of Disease Project, which has become one of the major public health problems in the world. , Liver fibrosis (LF) is considered to be a protective response to injury and is a common pathological feature of most chronic liver diseases. , The causes of LF are broad including chronic viral hepatitis B and C, autoimmune and biliary diseases, alcoholic steatohepatitis and nonalcoholic steatohepatitis (NASH), − and so on. The formation of LF is related to the activation of hepatic stellate cells (HSCs) and the secretion of an excessively deposited extracellular matrix (ECM).…”