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World Journal of Gastroenterology Mar 2014Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic liver disease characterized by immune-mediated destruction of the small- and medium-sized... (Review)
Review
Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic liver disease characterized by immune-mediated destruction of the small- and medium-sized intrahepatic bile ducts and the presence of antimitochondrial antibodies (AMA) in the serum. AMA are detected in over 90% of patients with PBC, whereas their prevalence in the general population is extremely low, varying from 0.16% to 1%. Previous studies have shown that the unique characteristics of biliary epithelial cells undergoing apoptosis may result in a highly direct and very specific immune response to mitochondrial autoantigens. Moreover, recent studies have demonstrated that serum from AMA-positive PBC patients is reactive with a number of xenobiotic modified E2 subunits of the pyruvate dehydrogenase complex, which is not observed in the serum of normal individuals. These findings indicate that chemicals originating from the environment may be associated with a breakdown in the tolerance to mitochondrial autoantigens. While it is currently generally accepted that AMA are the most specific serological markers of PBC, more than 60 autoantibodies have been investigated in patients with PBC, and some have previously been considered specific to other autoimmune diseases. This review covers the recent progress in research on the pathogenetic and clinical significance of important autoantibodies in PBC. Determining the pathogenic role of those autoantibodies in PBC remains a priority of basic and clinical research.
Topics: Animals; Antibodies, Antinuclear; Apoptosis; Autoantibodies; Autoimmunity; Bile Ducts, Intrahepatic; Biomarkers; Humans; Liver Cirrhosis, Biliary; Mitochondria; Prognosis
PubMed: 24627596
DOI: 10.3748/wjg.v20.i10.2606 -
Liver Transplantation and Surgery :... Sep 1998Liver transplantation is a highly effective treatment for patients with advanced primary biliary cirrhosis and primary sclerosing cholangitis. Transplantation is... (Review)
Review
Liver transplantation is a highly effective treatment for patients with advanced primary biliary cirrhosis and primary sclerosing cholangitis. Transplantation is indicated when the patient's survival with transplantation is better than without or, earlier than this, if the patient's quality of life is intolerable from intractable fatigue or pruritus. Medical therapies for chronic cholestatic liver diseases are very limited. Ursodeoxycholic acid therapy in primary biliary cirrhosis reduces cholestasis and prolongs transplant-free survival; no other drugs are of proven efficacy in primary biliary cirrhosis, and none have any benefit on the disease progression of primary sclerosing cholangitis. Aggressive endoscopic therapy may produce symptomatic and biochemical improvement in primary sclerosing cholangitis but should be done without the expectation of retarding disease progression. Bilirubin is one of five criteria of the Child-Turcotte-Pugh score, which is necessary for the United Network for Organ Sharing listing for orthotopic liver transplantation. In addition, it is a major prognostic indicator in all the predictive models for primary biliary cirrhosis. Bilirubin reduction with ursodeoxycholic acid therapy in primary biliary cirrhosis appears to parallel disease severity, and prognostic models utilizing bilirubin retain their predictive power for survival even in treated patients. In summary, medical therapies for chronic cholestatic liver disease have very little effect on disease progression and, subsequently, on the timing or selection for transplantation. Liver transplantation is the only definitive therapy for primary biliary cirrhosis and primary sclerosing cholangitis.
Topics: Cholagogues and Choleretics; Cholangitis, Sclerosing; Chronic Disease; Endoscopy; Female; Humans; Liver Cirrhosis, Biliary; Liver Transplantation; Male; Patient Selection; Prognosis; Quality of Life; Randomized Controlled Trials as Topic; Survival Rate; Time Factors; Treatment Outcome; Ursodeoxycholic Acid
PubMed: 9742489
DOI: No ID Found -
Journal of Autoimmunity 2007Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease characterized by inflammation and destruction of intrahepatic biliary epithelial cells, ultimately... (Review)
Review
Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease characterized by inflammation and destruction of intrahepatic biliary epithelial cells, ultimately leading to liver failure. The serological hallmark of PBC is the presence of high-titer antimitochondrial antibodies (AMA) against the inner lipoyl domain of E2 subunits of 2-oxo-acid dehydrogenase complexes, in particular the E2 component of the pyruvate dehydrogenase complex (PDC-E2). The initiating events triggering the autoimmune response are not yet identified but the hypothesis of molecular mimicry is a widely proposed mechanism for the development of autoimmunity in PBC. Several candidates, including bacteria and viruses, have been suggested as causative agents, but also environmental factors, such as chemical xenobiotics, have been implicated in the pathogenesis of primary biliary cirrhosis. In this review, we will discuss our current knowledge of the immunoreactivity of xenobiotically modified PDC peptide antigens. In addition, we will provide a working hypothesis how xenobiotic modification of antigens might occur that ultimately leads to the breaking of self-tolerance and the induction of PBC.
Topics: Animals; Autoantibodies; Autoimmune Diseases; Humans; Liver Cirrhosis, Biliary; Mitochondrial Proteins; Molecular Mimicry; Pyruvate Dehydrogenase Complex; Xenobiotics
PubMed: 17360156
DOI: 10.1016/j.jaut.2007.02.003 -
The Korean Journal of Hepatology Sep 2011Primary biliary cirrhosis (PBC) is a slowly progressive cholestatic liver disease of autoimmune etiology. The initial presentation of PBC is various from asymptomatic,... (Review)
Review
Primary biliary cirrhosis (PBC) is a slowly progressive cholestatic liver disease of autoimmune etiology. The initial presentation of PBC is various from asymptomatic, abnormal liver biochemical tests to overt cirrhosis. The diagnosis of PBC is based on cholestatic biochemical liver tests, presence of antimitochondrial antibody and histologic findings of nonsuppurative destructive cholangitis. Although the diagnosis is straightforward, it could be underdiagnosed because of its asymptomatic presentation, or underrecognition of the disease. UDCA in a dose of 13-15 mg/kg is the widely approved therapy which can improve the prognosis of patients with PBC. However, one-third of patients does not respond to UDCA therapy and may require liver transplantation. Every effort to diagnose PBC in earlier stage and to develop new therapeutic drugs and clinical trials should be made.
Topics: Autoantibodies; Autoimmunity; Cholagogues and Choleretics; Humans; Liver Cirrhosis, Biliary; Liver Transplantation; Ursodeoxycholic Acid
PubMed: 22102382
DOI: 10.3350/kjhep.2011.17.3.173 -
World Journal of Gastroenterology Jun 2008Primary biliary cirrhosis (PBC), which is characterised by progressive destruction of intrahepatic bile ducts, is not a rare disease since both prevalence and incidence... (Review)
Review
Primary biliary cirrhosis (PBC), which is characterised by progressive destruction of intrahepatic bile ducts, is not a rare disease since both prevalence and incidence are increasing during the last years mainly due to the improvement of case finding strategies. The prognosis of the disease has improved due to both the recognition of earlier and indolent cases, and to the wide use of ursodeoxycholic acid (UDCA). New indicators of prognosis are available that will be useful especially for the growing number of patients with less severe disease. Most patients are asymptomatic at presentation. Pruritus may represent the most distressing symptom and, when UDCA is ineffective, cholestyramine represents the mainstay of treatment. Complications of long-standing cholestasis may be clinically relevant only in very advanced stages. Available data on the effects of UDCA on clinically relevant end points clearly indicate that the drug is able to slow but not to halt the progression of the disease while, in advanced stages, the only therapeutic option remains liver transplantation.
Topics: Animals; Autoimmune Diseases; Bone Diseases, Metabolic; Cholagogues and Choleretics; Cholestyramine Resin; Disease Progression; Fatigue; Humans; Hyperlipidemias; Hypertension, Portal; Liver Cirrhosis, Biliary; Liver Transplantation; Malnutrition; Pruritus; Risk Factors; Treatment Outcome; Ursodeoxycholic Acid
PubMed: 18528929
DOI: 10.3748/wjg.14.3313 -
The Cochrane Database of Systematic... Oct 2004D-penicillamine is used for patients with primary biliary cirrhosis due to its hepatic copper decreasing and immunomodulatory potentials. The results from randomised... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
D-penicillamine is used for patients with primary biliary cirrhosis due to its hepatic copper decreasing and immunomodulatory potentials. The results from randomised clinical trials have been inconsistent.
OBJECTIVES
To systematically review the beneficial and harmful effects of D-penicillamine for patients with primary biliary cirrhosis.
SEARCH STRATEGY
We identified trials through electronic searches of The Cochrane Hepato-Biliary Group Controlled Trials Register (September 2003), The Cochrane Central Register of Controlled Trials on The Cochrane Library (Issue 3, 2003), MEDLINE (January 1966 to September 2003), EMBASE (January 1980 to September 2003), The Chinese Biomedical CD Database (January 1979 to August 2003), and LILACS (1982 to 2003); through manual searches of bibliographies; and by contacting authors of the trials and pharmaceutical companies.
SELECTION CRITERIA
We included randomised clinical trials comparing D-penicillamine with placebo/no intervention or other control intervention irrespective of language, year of publication, and publication status.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed the methodological quality of the trials and extracted data, validated by a third reviewer. The primary outcomes were 1) mortality and 2) a combination of those who died or underwent liver transplantation. We analysed dichotomous outcomes as relative risk (RR) with 95% confidence interval (CI) by a fixed effect model and a random effects model. We investigated sources of heterogeneity by subgroup analyses and tested the robustness of our findings by sensitivity analyses.
MAIN RESULTS
We included seven trials randomising 706 patients with primary biliary cirrhosis. D-penicillamine compared with placebo/no intervention tended to increase mortality (RR 1.34, 95% CI 1.09 to 1.64, fixed; RR 1.46, 95% CI 0.85 to 2.50, random). However, there was substantial heterogeneity. No significant differences were detected regarding the risks of mortality or liver transplantation, pruritus, liver complications, progression of liver histological stage, or the levels of liver biochemical variables (except alanine aminotransferase). D-penicillamine versus placebo/no intervention significantly increased the risk of adverse events (RR 3.11, 95% CI 2.33 to 4.16, fixed; RR 4.18, 95% CI 1.38 to 12.69, random).
REVIEWERS' CONCLUSIONS
D-penicillamine did not appear to reduce the risk of mortality, but significantly increased the occurrences of adverse events in patients with primary biliary cirrhosis. We do not support the use of D-penicillamine for patients with primary biliary cirrhosis.
Topics: Chelating Agents; Humans; Liver Cirrhosis, Biliary; Penicillamine; Randomized Controlled Trials as Topic
PubMed: 15495127
DOI: 10.1002/14651858.CD004789.pub2 -
Internal Medicine (Tokyo, Japan) 2011The natural history of the disease varies greatly among individual patients with primary biliary cirrhosis (PBC). Some patients live long without any symptoms while... (Review)
Review
The natural history of the disease varies greatly among individual patients with primary biliary cirrhosis (PBC). Some patients live long without any symptoms while other patients present jaundice and develop hepatic failure in early phases of the disease. Previous studies showed that the natural course of PBC is altered by the use of ursodeoxy cholic acid (UDCA). In this review we discuss variation in the natural course of the disease and it's alteration by UDCA, and risk factors that predict disease progression. Based on clinical observations, there are three types of clinical evolution in PBC: 1) minimal to slow progression over several years; 2) rapid progression to jaundice and hepatic failure, and 3) progression to portal hypertension without developing deep jaundice. Notably, based on our analyses accelerated progression to jaundice and liver failure are reflected by a sustained serologic presence of anti-gp210 antibodies whereas patients with portal hypertension in the absence of jaundice have anti-centromere autoantibodies. These observations highlight the clinical importance of antinuclear antibody analysis in patients with PBC.
Topics: Autoantibodies; Disease Progression; Genetic Predisposition to Disease; HLA-DR Antigens; HLA-DRB1 Chains; Humans; Liver Cirrhosis, Biliary; Liver Failure; Prognosis; Risk Factors; Ursodeoxycholic Acid
PubMed: 21212566
DOI: 10.2169/internalmedicine.50.4462 -
World Journal of Gastroenterology Apr 2006Primary biliary cirrhosis (PBC) is a disease of unknown etiology leading to progressive destruction of small intrahepatic bile ducts and eventually to liver cirrhosis... (Review)
Review
Primary biliary cirrhosis (PBC) is a disease of unknown etiology leading to progressive destruction of small intrahepatic bile ducts and eventually to liver cirrhosis and failure. It is characterised by female predominance and serum auto-antibodies to mitochondrial antigens targeting the E2 components of the 2-oxoacid dehydrogenase complex. Although they are associated with disease pathogenesis, no concrete evidence has been presented so far. Epidemiological data indicate that a geographical clustering of cases and possible environmental factors are implicated in pathogenesis. A number of genetic factors play a role in determining disease susceptibility or progression, although no definitive conclusion has been reached so far. A key factor to immune pathogenesis is considered to be the breakdown of immune tolerance, either through molecular mimicry or through the so called determinant density model. In this review, the available data regarding the pathogenesis of primary biliary cirrhosis are described and discussed. A new unifying hypothesis based on early endothelin overproduction in primary biliary cirrhosis (PBC) is presented and discussed.
Topics: Apoptosis; Autoantibodies; Humans; Liver Cirrhosis, Biliary; Mitochondria; Models, Biological; Molecular Mimicry; Reactive Oxygen Species; Self Tolerance; T-Lymphocytes
PubMed: 16688819
DOI: 10.3748/wjg.v12.i15.2320 -
Clinics in Liver Disease May 2008Primary biliary cirrhosis (PBC) is well known as a disease that predominantly affects women and has been hitherto only described in humans. The absence of an animal... (Review)
Review
Primary biliary cirrhosis (PBC) is well known as a disease that predominantly affects women and has been hitherto only described in humans. The absence of an animal model has significantly impaired research into both etiology and treatment. However, in the past 2 years, several spontaneous and two induced models of PBC were described. This article reviews the data on these animal models and places it in the perspective of human PBC and generic autoimmunity.
Topics: Animals; Disease Models, Animal; Humans; Liver Cirrhosis, Biliary; Mice; Mice, Inbred NOD; Receptors, Interleukin-2; Receptors, Transforming Growth Factor beta
PubMed: 18456184
DOI: 10.1016/j.cld.2008.02.011 -
World Journal of Gastroenterology Apr 2003To summarize the characteristics of patients suffered from primary biliary cirrhosis associated with ulcerative colitis. (Review)
Review
AIM
To summarize the characteristics of patients suffered from primary biliary cirrhosis associated with ulcerative colitis.
METHODS
To report a new case and review the literature.
RESULTS
There were 18 cases (including our case) of primary biliary cirrhosis complicated with ulcerative colitis reported in the literature. Compared with classical primary biliary cirrhosis, the patients were more often males and younger similar. The bowel lesions were usually mild with proctitis predominated. While ulcerative colitis was diagnosed before primary biliary cirrhosis in 13 cases, the presentation of primary biliary cirrhosis was earlier than that of ulcerative colitis in our new case reported here. The prevalence of primary biliary cirrhosis among patients of ulcerative colitis was almost 30 times higher than in general population.
CONCLUSION
Association of primary biliary cirrhosis with ulcerative colitis is rare. It should be considered in the differential diagnosis of hepatobiliary disease in patients with ulcerative colitis, and vice versa.
Topics: Adult; Aged; Biopsy; Colitis, Ulcerative; Colonoscopy; Diagnosis, Differential; Female; Humans; Liver Cirrhosis, Biliary; Male; Middle Aged
PubMed: 12679954
DOI: 10.3748/wjg.v9.i4.878