Primary Biliary Cholangitis: Its Pathological Characteristics and Immunopathological Mechanisms

Abstract

: Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is an organ-specific autoimmune disease that predominantly affects middle-aged women and is characterized by the chronic progressive destruction of small intrahepatic bile ducts with portal inflammation and, ultimately, fibrosis. The serological hallmark of PBC is the presence of anti-mitochondrial autoantibodies (AMA). Several mechanisms have been proposed for immune-mediated bile duct damage in PBC, including the roles of T cells, B cells, other cell phenotypes, and AMA. A sign of fragility of biliary epithelial cells caused by apoptosis, senescence, and autophagy has also been noted. Several complex steps and mechanisms appear to be involved in the induction and progression of cholangitis and biliary degeneration in patients with PBC.

Soluble CD163 and mannose receptor as markers of liver disease severity and prognosis in patients with primary biliary cholangitis

“…Hence, there is good reason to believe that the levels of sCD163 and sMR measured in our study stem from macrophages from the liver, which is also supported by a gradient across the liver as shown in alcohol cirrhosis and NASH patients 15,17 . Thus, our results suggest that macrophages play a pivotal role in disease development and progression in PBC, further supported by the known pathophysiological mechanism of PBC 7‐9 …”

“…The pathogenesis includes both CD4 and CD8 cells, which, in the presence of biliary cells expressing the 2‐oxo‐dehydrogenase pathway (PDC‐E2), activate macrophages via granulocyte macrophage colony‐stimulating factor. The activated macrophages, together with AMAs, produce a pro‐inflammatory response with subsequent liver inflammation and fibrosis 7‐9 . Furthermore, macrophages comprise around 30% of mononuclear cells found in the cellular infiltrate at biopsies in PBC patients 10 .…”

Primary Biliary Cholangitis and Ursodeoxycholic Acid: Therapy Progress and Challenges

“…Индекс конкордантности у монозиготных близнецов Гастроэнтерология № 3 (158), 2019 | | ГЕПАТОЛОГИЯ составляет 63% -он один из самых высоких среди таковых у прочих аутоиммунных заболеваний [23]. Наконец, при гистологическом исследовании плотные инфильтраты, состоящие из Т-и В-лимфоцитов, обнаруживаются вблизи пораженных внутрипеченочных желчных протоков [24]. Однако последние исследования выявили специфические генетически опосредованные предпосылки развития ПБХ.…”

Aging-Related Molecular Pathways in Chronic Cholestatic Conditions

“…This pathology is characterized by destruction of intrahepatic/extrahepatic bile ducts, chronic biliary inflammation, liver fibrosis (9,10) and is often associated with inflammatory bowel disease rising risks of developing colorectal cancer and cholangiocarcinoma (11)(12)(13). PBC, is an autoimmune disorder that specifically target cholangiocytes, characterized by the injury of small-and medium-sized bile ducts, cholestasis, and lymphocyte infiltration (14)(15)(16). Has been shown that PBC predominantly affects women, with higher incidence in patients who have a relative with PBC or any other autoimmune disorder (17).…”