Ursodeoxycholic acid reduces increased circulating endothelin 2 in primary biliary cirrhosis

Dimoulios, Philipos; Kolios, George; Notas, George; Matrella, Erminia; Xidakis, C.; Koulentaki, Mairi; Tsagarakis, Nikolaos J.; Kouroumalis, A.

doi:10.1111/j.1365-2036.2005.02307.x

Cited by 10 publications

(15 citation statements)

References 47 publications

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“…A significant increase of endothelins, particularly ET2 (and to a lesser extent of ET1) both in peripheral blood and in the hepatic vein of PBC patients from the early stages of the disease has been reported in our earlier study [179] . We then proposed a new hypothesis for the pathogenesis of PBC.…”

Section: Pathogenesis Of Pbc: a Unifying Hypothesissupporting

confidence: 70%

“…We therefore propose that patients with PBC an initiating damage of the biliary epithelium is caused by ischaemia due to ET2 induced vasoconstriction observed from the ealy stages PBC. This finding was disease specific since it was not observed in other chronic liver disease patient with or without cirrhosis [179] . Ischaemia might then lead to apoptosis of bile ductular cells a mechanism already reported in epithelial destruction of PBC.…”

Section: Pathogenesis Of Pbc: a Unifying Hypothesismentioning

confidence: 61%

“…We have suggested that an increase in ET2 observed from the early stages of the disease may be the initiative mechanism causing ischemic damage to cholangiocytes. UDCA treatment caused a significant reduction of ET2, possibly interrupting the early detrimental effect of ET2 [179] . A second mechanism may involve the CXCL chemokines.…”

Section: Mode Of Action Of Udcamentioning

confidence: 97%

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Primary biliary cirrhosis: From bench to bedside

Notas

2015

WJGPT

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Primary biliary cirrhosis (PBC) is a chronic nonsuppurative destructive intrahepatic cholangitis leading to cirrhosis after a protractive non cirrhotic stage. The etiology and pathogenesis are largely unknown and autoimmne mechanisms have been implicated to explain the pathological lesions. Many epitopes and autoantigens have been reported as crucial in the pathophysiology of the disease and T and B cells abnormalities have been described, the exact pathways leading to the destruction of small intrahepatic ductules are mostly speculative. In this review we examined the various epidemiologal and geoepidemiological data as well as the complex pathogenetic aspects of this disease, focusing on recent in vivo and in vitro studies in this field. Initiation and progression of PBC is believed to be a multifactorial process with strong infuences from the patient's genetic background and by various environmental factors. The role of innate and adaptive immunity, including cytokines, chemokines, macrophages and the involvement of apoptosis and reactive oxygen species are outlined in detailed. The current pathogenetic aspects are presented and a novel pathogenetic theory unifying the accumulated clinical information with in vitro and in vivo data is formulated.A review of clinical manifestations and immunological and pathological diagnosis was presented. Treatment modalities, including the multiple mechanisms of action of ursodeoxycholate were finally discussed. Core tip: Primary biliary cirrhosis (PBC) is a chronic nonsuppurative destructive intrahepatic cholangitis leading to cirrhosis of largely unknown pathophysiology. We examined the epidemiological and geoepidemiological data as well as the pathogenetic aspects of PBC. A novel pathogenetic theory unifying the accumulated clinical information with in vitro and in vivo data is formulated.

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Section: Pathogenesis Of Pbc: a Unifying Hypothesissupporting

confidence: 70%

Section: Pathogenesis Of Pbc: a Unifying Hypothesismentioning

confidence: 61%

Section: Mode Of Action Of Udcamentioning

confidence: 97%

See 1 more Smart Citation

Primary biliary cirrhosis: From bench to bedside

Notas

2015

WJGPT

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“…Incubation with HBV sera yielded positive staining of the hepatocytes, intra-sinusoidal and portal lymphocytes and cholangiocytes of some PBC ( Figure 3A-C tissue, we have identified sinusoidal cells as liver cells targeted by circulating autoantibodies in PBC patients. We previously hypothesized that the primary event in PBC is the excessive production of endothelin 2, possibly by sinusoidal cells [21,22] . The role of certain autoantibodies in PBC is well …”

Section: Sections From Disease Controls or Sections Of Normal Controlmentioning

confidence: 99%

“…In our previous studies, we hypothesized that the primary initiating event in PBC may be the overproduction of endothelins by liver sinusoidal cells [21,22] . The aim of the present study was therefore to identify the presence of circulating antibodies against liver sinusoidal cells in PBC patients.…”

Section: Introductionmentioning

confidence: 99%