Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholestatic liver disease is primarily caused by impaired bile production on the level of hepatocytes and cholangiocytes. Clinically cholestasis can be divided into intrahepatic and extrahepatic forms based on the presence or absence of dilated bile ducts (sonography). Intrahepatic cholestasis is most frequently caused by end stage liver cirrhosis followed by primary cholangiopathies and canalicular transport defects in hepatocytes. The causes of the most important cholangiopathies, such as Primary Biliary Cirrhosis (PBC) and Primary Sclerosing Cholangitis (PSC) are so far not known. Therefore, drug therapy of cholestatic liver disease focuses on the improvement of symptoms such as fatigue, pruritus, abdominal discomfort, jaundice, xanthoma, hypercholesterolemia, portal hypertension, blood count abnormalities, osteoporosis/osteomalacia, and the prevention of complications such as bile-duct strictures in PSC and development of cholangiocarcinoma. The first choice drug in the treatment of cholestatic liver disease of various causes is urosodeoxycholic acid (UDCA), that has been shown to decrease bile acid toxicity in general and prolong the transplant free survival of patients with PBC. If cholestasis persists cirrhosis of the liver is the major complication and liver transplantation may be the definitive treatment in advanced cases of cholestatic liver disease.
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PMID:[Cholestatic liver diseases]. 945 66

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) share many clinical and pathologic features. Central to the symptoms and biochemical alterations of both conditions is a substantial loss of intrahepatic bile ducts, leading to interference with bile flow. This pathologic change may ultimately result in cirrhosis of the biliary type. In addition, however, biopsy specimens usually show an element of liver-cell destruction and associated inflammation, mainly interface hepatitis. This finding is more pronounced in PBC than in PSC but can lead in both diseases to features that resemble those of cirrhosis as a result of hepatitis virus infection. The resemblance often leads to diagnostic confusion, which is easily overcome by attention to the clinical, radiologic, serologic, and biochemical context. Histologic staging of PBC and PSC has led to a greater appreciation of their evolution but is hampered in biopsy material by sampling error. Examination of explanted livers at transplantation has demonstrated a wide variation in the maturation of lesions in various parts of the organ.
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PMID:Ludwig Symposium on biliary disorders--part II. Pathologic features and evolution of primary biliary cirrhosis and primary sclerosing cholangitis. 947 3

Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic liver disease whose aetiopathogenesis is unknown. PSC is frequently associated with inflammatory bowel disease, in particular chronic ulcerative colitis, is most commonly observed in young males and is clinically characterized by fatigue, pruritus and jaundice. The diagnosis is supported by a cholestatic biochemical profile and histological abnormalities, and confirmed by visualization of an abnormal biliary tree. The natural history of the disease is currently being evaluated but is generally recognized to be slowly progressive, leading to complications of chronic cholestasis, portal hypertension and biliary cirrhosis. There is no specific medical treatment, and orthotopic liver transplantation remains the only definitive treatment for patients with end-stage PSC. A more rational approach to medical therapy will ensue upon a better understanding of the aetiopathogenesis of this disease.
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PMID:Sclerosing cholangitis. 951 10

Primary sclerosing cholangitis (PSC) is a cholestatic liver disease characterized by fibro-obliterative inflammation of the entire biliary tree. It is a slowly progressive disease with an undulating course, resulting in terminal biliary cirrhosis after a median period of about 12 years after diagnosis. The etiology of the disease is unknown and there is no effective therapy that can halt disease progression. Around 8% of PSC patients develop cholangiocarcinoma, which, by the time it is diagnosed, cannot be treated curatively. The purpose of this article is to review the current knowledge about primary sclerosing cholangitis and to speculate on future strategies to address the issues of etiology and therapy.
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PMID:Primary sclerosing cholangitis: a clinical review. 957 40

We present here three paediatric patients with primary sclerosing cholangitis. In case 1, the serum gamma-glutamyl transpeptidase was decreased only temporarily by ursodeoxycholic acid (UDCA) treatment and 34 months later, sulphasalazine was added because of microscopic colitis. The enzyme level decreased with dual therapy. Similarly, in case 3, first diagnosed as autoimmune hepatitis, the transpeptidase levels remained elevated for 18 months during treatment with UDCA, prednisolone and mizoribin. The enzyme decreased only after a diagnosis of primary sclerosing cholangitis complicated with ulcerative colitis was established and sulphasalazine was introduced. Case 2 also had Crohn's colitis and was put on UDCA and sulphasalazine from the start. The enzyme level was normalized within 1 month and has remained normal for the following 5 years. Liver biopsies were analysed repeatedly in these three patients. In case 1, periductal fibrosis remained unchanged while being treated by UDCA. There appeared to be no progression in liver cirrhosis in case 3 while being treated by UDCA, prednisolone, and mizoribin. In case 2, who has been treated with both UDCA and sulphasalazine from the start, periductal fibrosis and portal fibrosis were remarkably improved 45 months later. We suggest that sulphasalazine in addition to UDCA might be a viable treatment for children with primary sclerosing cholangitis.
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PMID:Three paediatric cases of primary sclerosing cholangitis treated with ursodeoxycholic acid and sulphasalazine. 973 77

Idiopathic adult ductopenia is very rare. We report one case in a 30-year-old man, whose clinical course was characterized by jaundice and pruritus. Laboratory investigations revealed cholestasis and polyclonal hypergammaglobulinemia. Serum antinuclear, antimitochondrial, and anti-smooth muscle antibodies and serological markers for viral hepatitis were negative. Endoscopic retrograde cholangiography showed no liver or biliary tract abnormalities. Histological examination of a liver specimen showed a vanishing bile duct syndrome and moderate portal infiltration with lympho-histiocytic cells; there were no granulomas. Liver transplantation was performed due to rapid development of cirrhosis. The differential diagnosis of idiopathic adult ductopenia with small duct primary sclerosing cholangitis, auto-immune cholangiopathy, and non syndromic paucity of intrahepatic bile ducts is unclear.
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PMID:[Adult idiopathic ductopenia. 1 case]. 976 95

Anti-neutrophil cytoplasmic antibodies (ANCA) are autoantibodies directed against cytoplasmic constituents of neutrophil granulocytes. Antibodies with specificity for proteinase 3 and myeloperoxidase are seromarkers for systemic vasculitides. ANCA with specificity for lactoferrin were described in patients with several idiopathic inflammatory diseases, such as the inflammatory bowel diseases and rheumatoid arthritis. However, the clinical significance of anti-lactoferrin autoantibodies is still unclear. In this study, we determined the clinical significance of anti-lactoferrin autoantibodies in sera from large groups of patients with ulcerative colitis (UC), Crohn's disease (CD), and primary sclerosing cholangitis (PSC). Antibodies to human lactoferrin were detected by ELISA and by immunoblotting, using an extract of sonicated neutrophils as antigen source. Autoantibodies to lactoferrin were found in 29% of patients with UC, 13% of patients with CD, and 22% of patients with PSC. In inflammatory bowel diseases, the presence of anti-lactoferrin antibodies was not related to treatment, disease activity, duration of disease, or disease extent. In PSC, the presence of autoantibodies to lactoferrin did not correlate with duration of disease or the presence of cirrhosis. However, patients with PSC and coexistent UC had significantly more frequently antibodies to lactoferrin than PSC patients without IBD. In conclusion, autoantibodies to lactoferrin are a common feature of inflammatory bowel diseases and PSC. However, the clinical significance of those autoantibodies is limited as they lack sensitivity and specificity for those disorders. Future research should address the pathophysiological role of anti-lactoferrin ANCA and the influence of anti-lactoferrin ANCA binding on the functional properties of the lactoferrin molecule.
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PMID:Prevalence and clinical significance of anti-lactoferrin autoantibodies in inflammatory bowel diseases and primary sclerosing cholangitis. 978 75

Primary sclerosing cholangitis (PSC) is generally associated with ulcerative colitis (UC). The disease typically progresses slowly, but ultimately, and leads to cirrhosis, liver failure or bile duct cancer. PSC patients with simultaneous ulcerative colitis are also at higher risk for colorectal cancer. At the present time, there is no effective treatment for PSC, although preliminary data show encouraging results after treatment with ursodeoxycholic acid. However, there are no data concerning the delay or prevention of progress of the disease with this drug, because follow-up time is not yet long enough. Isolated bile duct strictures should be treated endoscopically. The possible effect of proctocolectomy on the course of PSC is controversial. Liver transplantation is the therapy of choice for PSC in its final stage. The 5-year survival rate (89%) is significantly better than after transplantation for other indications. Patients with ulcerative colitis have to be followed up by lifelong colonoscopy. Although the course of UC after transplantation is mostly asymptomatic, these patients are at higher risk for colorectal cancer.
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PMID:[Primary sclerosing cholangitis--an ulcerative colitis-associated illness with surgical consequences]. 983 81

The clinical histories of 46 adult patients (24 men and 22 women, mean age 20.6 +/- 5.1 years) diagnosed of cystic fibrosis were reviewed evaluating the digestive alterations. The age at diagnosis of cystic fibrosis was 5.63 +/- 5.3 years (range: newborns-19 years). The initial diagnosis was established by ileus meconium, in four, lung disease in 15, steatorrhea in 12, lung disease and steatorrhea in 13 and following the diagnosis of cystic fibrosis in siblings in two. Four patients presented ileus meconium, nine occlusive syndrome of the distal intestine, 42 steatorrhea (20 severe, 12 moderate and 10 mild), with the severity of the steatorrhea not being associated with the severity of the respiratory insufficiency. Two patients presents rectal prolapse, five gastroesophageal reflux syndrome (four with hiatal hernia), six cholelithiasis, one recurrent pancreatitis without detection of biliary lithiasis, one neonatal cholestasis and 10 malnutrition (five severe and five moderate) fundamentally in relation to the severity of the lung disease and, to a lesser degree, liver disease. In 10 patients chronic liver disease was diagnosed corresponding to established cirrhosis in seven, indicating liver transplantation in two. In most cases, the liver disease was already manifest in adolescence even in the cirrhotic stage. Cholangiography by magnetic resonance was useful in the study of liver disease showing abnormalities which imitated primary sclerosing cholangitis. Treatment with ursodesoxicholic acid at a dosis of 20 mg/kg/day led to a significant decrease in the transaminase values and overall of gammaglutamyltranspeptidase but did not avoid complications in the cirrhotic stages. Genetic studies performed in 36 patients detected the delta F508 mutation in 69.4%, being found in almost all of the patients with ileus meconium, occlusive syndrome of the distal intestine, liver disease, cholelithiasis and malnutrition.
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PMID:[Digestive alterations in cystic fibrosis. Retrospective study of a series of 46 adult patients]. 1019 90

Primary sclerosing cholangitis is a generally progressive, sometimes fatal, chronic hepatobiliary disorder for which no effective medical or surgical therapy now exists. The syndrome occurs most frequently in young men and is characterized by chronic cholestasis, frequent association with CUC, a paucity of serologic markers, hepatic copper overload, and characteristic abnormalities in some liver biopsy specimens and in virtually all cholangiograms. The natural history of the syndrome is still somewhat unclear; the disease likely progresses slowly and relentlessly over a decade or longer from an asymptomatic stage to a condition characterized by symptoms of cholestasis and complicated by cirrhosis and portal hypertension and carcinoma of the bile ducts. Management should first involve a thoughtful decision to observe, which is reasonable in the asymptomatic patient with early disease, or to intervene, particularly in patients with symptoms. Therapeutic goals should be defined and should concentrate on either alleviating symptoms, dealing with complications, or attempting to affect the underlying hepatobiliary disease. Symptomatic treatment and therapy for complications is similar to that employed in other chronic liver diseases, but also involves balloon dilatation of dominant strictures in appropriately selected symptomatic patients. Biliary tract reconstructive surgery may alleviate symptoms in selected patients with PSC, but its effect on the natural history of the syndrome has not been determined. Proctocolectomy for CUC in a patient with CUC and PSC does not beneficially affect the progression of the underlying hepatobiliary disease. In contrast, orthotopic liver transplantation may be life-saving for patients with advanced disease. Medical therapy directed at arresting the progression of the underlying hepatobiliary disease is currently experimental and includes cupruretic, immunosuppressive, antifibrogenic, and choleretic agents. Although a single recently completed controlled trial makes it unlikely that cupruretic agents will be helpful in this syndrome, immunosuppressive (i.e. cyclosporin A and methotrexate) and choleretic (i.e. ursodeoxycholic acid) agents alone or in combination are currently undergoing evaluation in randomized trials.
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PMID:The Fifth Carlos E. Rubio Memorial Lecture. Sclerosing cholangitis: pathogenesis, pathology, and practice. 1034 81


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