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Annals of Transplantation Sep 2014Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver, characterized by the presence of antimitochondrial antibodies (AMA) and progressive... (Review)
Review
Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver, characterized by the presence of antimitochondrial antibodies (AMA) and progressive immune-mediated destruction of biliary ductules, which lead to cirrhosis. Theories of the PBC etiopathogenesis assume that the disease develops secondarily as an improper immunological reaction to undefined environmental and/or infectious factors in genetically predisposed individuals. Ursodeoxycholic acid (UDCA) is the only drug recommended to treat PBC; it delays the progression of liver disease, but remains only a symptomatic treatment. In the advanced stage of PBC, the treatment of choice is liver transplantation (LTx). Nowadays, PBC is the third indication for LTx, after viral-related and alcoholic liver cirrhosis. Unfortunately, PBC recurs in 21-37% of patients at 10 years after LTx, and in 43% at 15 years after LTx, with the median time to recurrence of 3-5.5 years. Diagnosis of recurrent PBC (rPBC) is based on the liver histopathology. Although various risk factors of rPBC have been investigated, the cause of the recurrence is not clear. There is no specific treatment of rPBC. Together with immunosuppression after LTx, UDCA remains the treatment of choice. New diagnostic technologies (e.g., genomics, proteomics, cell-based therapy, and clinical study of the rPBC patients) may be helpful in understanding the pathogenesis of PBC and the development of new treatment modalities.
Topics: Cholagogues and Choleretics; Humans; Immunosuppression Therapy; Liver Cirrhosis, Biliary; Liver Transplantation; Recurrence; Risk Factors; Ursodeoxycholic Acid
PubMed: 25262831
DOI: 10.12659/AOT.890753 -
Journal of Gastrointestinal and Liver... Dec 2016Primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) are the most common immune-mediated chronic cholestatic liver diseases leading to cirrhosis and... (Review)
Review
Primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) are the most common immune-mediated chronic cholestatic liver diseases leading to cirrhosis and liver failure. Although magnetic resonance imaging (MRI) is not a necessary procedure for the diagnosis of PBC, MRI is recommended for monitoring disease progression and early detection of complications. Even though liver cirrhosis subtypes have similar MR imaging features, there are some findings which could indicate PBC, such as the periportal halo sign. Additionally, MRI using diffusion-weighted imaging with apparent diffusion coefficient measurements provides non-invasive assessment of the stage of liver fibrosis. The role of cholangiography is crucial for the diagnosis of PSC. Since endoscopic retrograde cholangiography is an invasive procedure with occasional post-procedural complications, the latest guidelines suggest magnetic resonance cholangiography as a reference procedure for evaluation of patients suspected with PSC. Characteristic magnetic resonance cholangiography findings include multiple segmental strictures with slightly dilated ducts among them, usually on both intrahepatic and extrahepatic bile ducts. Furthermore, magnetic resonance cholangiography is useful in the follow-up of these patients, allowing for timely diagnosis of complications such as cholangiocellular carcinoma. With the exception of ursodeoxycholic acid, which slows the progression of PBC, the only curative treatment for both PSC and PBC is still liver transplantation. However, recurrent disease occurs in some patients indicating the need for development of new more effective therapies.
Topics: Adult; Bile Ducts; Cholangiopancreatography, Magnetic Resonance; Cholangitis, Sclerosing; Diffusion Magnetic Resonance Imaging; Female; Humans; Liver; Liver Cirrhosis, Biliary; Male; Middle Aged; Predictive Value of Tests; Prognosis
PubMed: 27981308
DOI: 10.15403/jgld.2014.1121.254.vac -
The Yale Journal of Biology and Medicine 1997Previous studies suggested endotoxin, derived from the intestine through the portal blood to the liver, was predominantly metabolized by Kupffer cells. In the present... (Review)
Review
Previous studies suggested endotoxin, derived from the intestine through the portal blood to the liver, was predominantly metabolized by Kupffer cells. In the present study, fluorescent-labeled endotoxin injected into the rat portal vein was demonstrated not only in Kupffer cells but also in hepatocytes. Furthermore a great amount of labeled endotoxin was recovered in bile. In the livers of patients with primary biliary cirrhosis (PBC), immunohistochemistry demonstrated significant retention of endotoxin in the biliary epithelial cells, and treatment with ursodeoxycholic acid significantly reduced the retention in those cells. The study for detection of apoptosis demonstrated increased rates of apoptosis in hepatocytes and biliary epithelial cells in PBC liver, and the rate of apoptosis in biliary epithelial cells was significantly reduced after treatment with ursodeoxycholic acid. Immunohistochemistry in PBC liver demonstrated significant reduction of fluorescence intensity for a 7H6 antigen in biliary epithelial cells, indicating the increased paracellular permeability of bile ducts, because cellular immunolocalization of that antigen has been shown to be inversely correlated with the paracellular permeability of the tight junction. These results suggest that, in biliary epithelial cells, retention of endotoxin, increased apoptosis, and increased permeability of tight junctions may be involved in the pathogenesis of PBC.
Topics: Animals; Apoptosis; Bile Ducts; Biliary Tract; Cell Membrane Permeability; Endotoxins; Epithelial Cells; Humans; Liver; Liver Cirrhosis, Biliary; Rats
PubMed: 9626760
DOI: No ID Found -
Medical Science Monitor : International... 2000Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease that predominantly occurs in middle-aged women of various ethnic and racial populations. The... (Review)
Review
Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease that predominantly occurs in middle-aged women of various ethnic and racial populations. The disease slowly progresses over decades and is supposed to be caused by immune reactions against host antigens. Histologically, it is characterized by inflammatory destruction of intrahepatic small bile ducts, subsequent fibrosis, and finally liver cirrhosis. It is more frequently diagnosed now than in the past probably because of a greater awareness of the disease. There is only week association of PBC with genetic markers. Liver function tests reveal an elevation of serum alkaline phosphatase and gamma-glutamyl transpeptidase levels with or without elevated aminotransferase levels. The hallmark of the disease is the presence of antimitochondrial antibodies (AMAs), which are found in 95% of patients with PBC. AMAs have been shown to be directed against the 2-oxo-acid dehydrogenase complexes located on the inner membrane of the mitochondria. However, AMA titers do not correlate with the disease severity of progression, and the role of AMAs in the pathogenesis of PBC has not been shown. The disease is frequently associated with other autoimmune diseases, including Sjögren's syndrome, scleroderma and thyroid disorders. Most therapeutic efforts have been directed at altering the immune response. Ursodeoxycholic acid (UDCA) appears to be effective therapy in preventing or delaying the need for liver transplantation and improving survival. However, a number of patients receiving UDCA still develop progressive disease and go on to transplantation, which is an effective therapy at the end stage of the disease. Various prognostic models have been proposed to estimate the survival probability and assist in the determination of the optimum timing of liver transplantation.
Topics: Autoantibodies; Autoimmune Diseases; Diagnosis, Differential; Humans; Liver Cirrhosis, Biliary; Liver Transplantation; Mitochondria; Prognosis; Ursodeoxycholic Acid
PubMed: 11208308
DOI: No ID Found -
International Journal of Molecular... Nov 2016Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) represent the major clinical entities of chronic cholestatic liver diseases. Both disorders are... (Review)
Review
Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) represent the major clinical entities of chronic cholestatic liver diseases. Both disorders are characterized by portal inflammation and slowly progress to obliterative fibrosis and eventually liver cirrhosis. Although immune-pathogenic mechanisms have been implicated in the pathogenesis of PBC and PSC, neither disorder is considered to be a classical autoimmune disease, as PSC and PBC patients do not respond to immune-suppressants. Furthermore, the decreased bile flow resulting from the immune-mediated tissue assault and the subsequent accumulation of toxic bile products in PBC and PSC not only perpetuates biliary epithelial damage, but also alters the composition of the intestinal and biliary microbiota and its mutual interactions with the host. Consistent with the close association of PSC and inflammatory bowel disease (IBD), the polyclonal hyper IgM response in PBC and (auto-)antibodies which cross-react to microbial antigens in both diseases, an expansion of individual microbes leads to shifts in the composition of the intestinal or biliary microbiota and a subsequent altered integrity of epithelial layers, promoting microbial translocation. These changes have been implicated in the pathogenesis of both devastating disorders. Thus, we will discuss here these recent findings in the context of novel and alternative therapeutic options.
Topics: Anti-Bacterial Agents; Antibodies, Bacterial; Bacterial Translocation; Bile; Cholangiopancreatography, Endoscopic Retrograde; Cholangitis, Sclerosing; Gastrointestinal Microbiome; Host-Pathogen Interactions; Humans; Immunoglobulin M; Liver Cirrhosis, Biliary
PubMed: 27834858
DOI: 10.3390/ijms17111864 -
Disease Markers 2010Primary biliary cirrhosis (PBC) is an autoimmune disease of unclear etiology. It is a chronic, progressive condition that causes intrahepatic ductal destruction... (Review)
Review
Primary biliary cirrhosis (PBC) is an autoimmune disease of unclear etiology. It is a chronic, progressive condition that causes intrahepatic ductal destruction ultimately leading to symptoms of cholestasis, cirrhosis and liver failure. The disease predominantly affects middle aged Caucasian women. It has a predilection to certain regions and is found in higher incidences in North America and Northern Europe. It also has a genetic predisposition with a concordance rate of 60% among monozygotic twins. Combinations of genetic and environmental factors are proposed in the pathogenesis of this disease with a compelling body of evidence that suggests a role for both these factors. This review will elucidate data on the proposed environmental agents involved the disease's pathogenesis including xenobiotic and microbial exposure and present some of the supporting epidemiologic data.
Topics: Animals; Environmental Exposure; Genetic Predisposition to Disease; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Liver Cirrhosis, Biliary; Risk Factors; Xenobiotics
PubMed: 21297251
DOI: 10.3233/DMA-2010-0770 -
BMJ (Clinical Research Ed.)
Topics: Clinical Trials as Topic; Humans; Liver Cirrhosis, Biliary; Treatment Outcome; Ursodeoxycholic Acid
PubMed: 8086896
DOI: 10.1136/bmj.309.6953.491 -
Journal of Hepatology May 2010Primary biliary cirrhosis (PBC) is a chronic inflammatory autoimmune disease that mainly targets the cholangiocytes of the interlobular bile ducts in the liver. The... (Review)
Review
Primary biliary cirrhosis (PBC) is a chronic inflammatory autoimmune disease that mainly targets the cholangiocytes of the interlobular bile ducts in the liver. The condition primarily affects middle-aged women. Without treatment, PBC generally progresses to cirrhosis and eventually liver failure over a period of 10-20 years. PBC is a rare disease with prevalence of less than 1/2000. PBC is thought to result from a combination of multiple genetic factors and superimposed environmental triggers. The contribution of the genetic predisposition is evidenced by the familial clustering. Several risk factors, including exposure to infectious agents and chemical xenobiotics, have been suggested. Ursodeoxycholic acid (UDCA) is currently the only FDA-approved medical treatment for PBC. When administered at doses of 13-15 mg/kg/day, a majority of patients with PBC have a normal life expectancy without additional therapeutic measures. One out of three patients does not adequately respond to UDCA therapy and may need additional medical therapy and/or liver transplantation. This review summarises current knowledge on the epidemiology, ethiopathogenesis, clinical, and therapeutic aspects of PBC.
Topics: Diagnosis, Differential; Environment; Genetic Predisposition to Disease; Hepatitis; Humans; Liver Cirrhosis, Biliary; Liver Diseases; Lymphocytes; Prevalence; Prognosis; Risk Factors
PubMed: 20347176
DOI: 10.1016/j.jhep.2009.11.027 -
The Israel Medical Association Journal... Jan 2011Primary biliary cirrhosis (PBC) is considered a model autoimmune disease because of the similarities between patients, their relative homogeneous presentation and... (Review)
Review
Primary biliary cirrhosis (PBC) is considered a model autoimmune disease because of the similarities between patients, their relative homogeneous presentation and natural history, and the presence of the signature autoantibody, the antimitochondrial antibodies. PBC also illustrates the potential role of genetic and environmental influence and is unique in having several well-defined animal models that recapitulate distinct features of the disease. The pathogenesis of the disease includes genetic predisposition, the production of both innate and adaptive immune responses, and cholangiocyte-specific biology that addresses the specificity of disease. In this review we highlight these features of PBC in comparison to other autoimmune diseases.
Topics: Humans; Liver Cirrhosis, Biliary
PubMed: 21446239
DOI: No ID Found -
Journal of Internal Medicine May 1997
Review
Topics: Autoimmune Diseases; Causality; Disease Progression; Genetic Predisposition to Disease; Humans; Immunotherapy; Liver Cirrhosis, Biliary; Liver Transplantation
PubMed: 9183301
DOI: 10.1046/j.1365-2796.1997.127138000.x