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)

To investigate whether sclerosing cholangitis with an autoimmune serology characteristic of autoimmune hepatitis (AIH) and AIH are distinct entities, we studied 55 consecutive children with clinical and/or biochemical evidence of liver disease and circulating antinuclear (ANA), anti-smooth muscle (SMA), and/or liver-kidney-microsomal type 1 (LKM1) autoantibodies. They underwent liver biopsy, direct cholangiography, sigmoidoscopy, and rectal biopsy at presentation. Twenty-eight were diagnosed as AIH in the absence and 27 autoimmune sclerosing cholangitis (ASC) in the presence of radiological features of cholangiopathy. Twenty-six ASC and 20 AIH had ANA and/or SMA; 1 ASC and 8 AIH LKM1 autoantibody. Similarities between the 2 conditions included most clinical and biochemical parameters and a lower frequency of HLA DR4. Inflammatory bowel disease and histological biliary changes were more common in ASC; coagulopathy, hypoalbuminemia, lymphocytic periportal hepatitis, and HLA DR3 were more common in AIH. Histological biliary changes were observed in 65% of ASC and 31% of AIH patients. Eighty-nine percent responded to immunosuppression. Follow-up liver biopsies from 17 ASC and 18 AIH patients had similarly reduced inflammatory activity and no progression to cirrhosis. Sixteen follow-up cholangiograms from AIH patients and 9 from ASC patients were unchanged, while 8 ASC patients showed a progressive cholangiopathy. One child with AIH and ulcerative colitis developed sclerosing cholangitis 8 years after presentation. At 2 to 16 years (median, 7 years) from presentation, all patients are alive, including 4 ASC patients who underwent liver transplantation. In conclusion, ASC and AIH are similarly prevalent in childhood; cholangiography is often needed to distinguish between these 2 entities, which are likely to lie within the same disease process.
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PMID:Autoimmune hepatitis/sclerosing cholangitis overlap syndrome in childhood: a 16-year prospective study. 1123 Jul 33

The diagnosis of biliary disease, namely malignant disorders, is frequently hampered by the inconclusive cytology. We investigated prospectively the frequency of molecular changes in p53 and ras compared with cytology in patients with primary or secondary hepato-biliary disease. We investigated 118 consecutive patients, aged 24-89 with the following clinical diagnoses: choledocho/cholecystolithiasis (28), cholangiocellular carcinoma (21), gall bladder tumor (8), liver metastasis (3), autoimmune disease (8), chronic pancreatitis (16), pancreatic carcinoma (11), papillary disease (4), hepatic cirrhosis (6), cholangitis (2), anomalies (2), and normal (9). Bile was aspirated during routine endoscopic retrograde cholangio pancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC). DNA was prepared freshly from a native aliquot. p53 mutations were detected by polymerase chain reaction (PCR) for exons 5 through 8 followed by TGGE. PCR for ras mutations was performed as RFLP-PCR with sequencing. In four cases, mutations in p53 could be found in exons 6 and 7. Twenty-two samples showed ras mutations; ras mutations were found in choledocholithiasis (4/28), bile duct (5/21), gall bladder (3/8) and pancreatic (1/11) carcinoma, liver metastasis (3/3), ulcerative colitis (2/3), PSC (1/2), and chronic pancreatitis (1/16). Cytology was clearly positive in seven cases, suspicious in three other, inconclusive in six, and negative in the rest. The molecular analysis resulted in a sensitivity of 33% and specificity of 87%, respectively, for the diagnosis of a malignant condition. PCR for p53 and ras mutations may aid the diagnosis of primary and secondary (metastatic) hepatobiliary disease if a malignant condition of the bile ducts and the liver is suspected and cytology is inconclusive or negative. However, the incidence of p53 and ras mutations in bile seems less frequent than in other malignant conditions of the gastrointestinal tract and the pancreas and lower than in tissue, leaving a poor sensitivity and specificity. Nevertheless, the presence of a p53 and/or ras mutation per se supports a clinical suspicion of malignancy, even when the conventional cytology is negative or inconclusive.
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PMID:Low frequency of p53 and ras mutations in bile of patients with hepato-biliary disease: a prospective study in more than 100 patients. 1126 52

We report the case of a 66-year-old male with ulcerative colitis diagnosed in 1987, who had been treated with azathioprine (AZA) for the past two years (average dose about 1.6 mg/kg/day). In May 1999 he presented with painless jaundice, fatigue and recent weight loss. Cholestatic enzymes were elevated, alpha-fetoprotein was normal and hepatitis B/C serology negative. After diagnosis of veno-occlusive disease (VOD) and hepatocellular carcinoma (HCC) via biopsy, tumour resection was performed. The histology was typical for a well-differentiated HCC with trabecular and pseudoglandular structures. Neighbouring liver tissue was atrophic, with nodular regenerative hyperplasia (NRH), peliosis-like sinusoidal ectasias and intra-sinusoidal accumulation of blood, associated with peri-sinusoidal fibrosis. Although none of the well-established risk factors for HCC such as cirrhosis, hepatitis B/C, metabolic liver disease or toxins were present, this patient developed HCC. This and previous reports suggest that NRH and/or VOD associated with AZA represent a risk factor for HCC. AZA should therefore not only be stopped in patients with NRH/VOD but patients should also be screened for HCC.
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PMID:Veno-occlusive disease, nodular regenerative hyperplasia and hepatocellular carcinoma after azathioprine treatment in a patient with ulcerative colitis. 1129 51

Carcinoembryonic antigen (CEA) is an oncofoetal protein first identified by Gold and Freedman (1965) in colorectal cancer. It is a cell surface tumor marker which has been characterised as a heterogenous group of glycoproteins. It is also present in a variety of benign and non-neoplastic diseases like ulcerative colitis, Adenomatous polyp, Liver cirrhosis and other cancers like GI tract tumors, Cancer of the breast, lung, ovary, pancreas, prostate, hepatoma etc. Elevated CEA levels serve as clinical tool in the diagnosis, monitoring, detecting early any recurrence or metastasis and in prognostication for confirmed colorectal cancers. In order to develop an Enzyme Immuno Assay and immunocytochemical assay for CEA, an MAb designated as CIBCHTB1 has been generated using CEA isolated from a cell line HT115, human adenocarcinoma of the colon, as immunogen by the conventional Hybridoma technology. This MAb of IgG1 isotope was selected by screening of culture supernatents by ELISA and then by its high binding affinity with HT115 cells as revealed by flowcytometric analysis. By ABC method of immunocytochemical assay, this Ab exhibited strong staining of cells in frozen tissue sections of normal colon and malignant colorectal lesions and various other types of human cancers. This MAb has useful application to study the expression of CEA in human cancers. Serum CEA levels of patients with colorectal cancers and other CEA producing cancers and controls determined by EIA using this MAb were in good correlation with the results obtained using commercial kit. The diagnostic potential of this Mab in the management of colorectal cancers is discussed.
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PMID:Monoclonal antibody CIBCHTB1 defining an epitope on carcinoembryonic antigen (CEA). 1134 Nov 76

In four cases we describe the unique association of primary sclerosing cholangitis (PSC) and rheumatoid arthritis (RA). In three of the cases the liver disease was unusually progressive, proceeding to cirrhosis in 14, 18 and 48 months from diagnosis. The three cases with progressive liver disease and ulcerative colitis were all HLA type DR4. The fourth patient also suffered from coeliac disease in addition to PSC and RA and has remained asymptomatic over 7 years of follow-up. RA in association with PSC may serve as a clinical marker of patients at high risk of progression to cirrhosis who need to be kept under particularly close observation. In addition, PSC needs to be considered in the differential diagnosis of all patients with RA and cholestatic liver function tests. This is especially important given the link between PSC and an increased risk of colonic carcinoma, and thus the need for surveillance colonoscopy.
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PMID:Primary sclerosing cholangitis associated with rheumatoid arthritis and HLA DR4: is the association a marker of patients with progressive liver disease? 1139 67

Since the aetiopathogenesis of primary sclerosing cholangitis (PSC) in humans remains undefined, investigators have studied a variety of animal models to gain insights into immunopathogenetic mechanisms associated with obliterative fibrous cholangitis of intra- and extra-hepatic bile ducts. To date, no animal model has been developed that exhibits all of the attributes of PSC. Rodent models instigated by bacterial cell components or colitis are promising because they may help to explain the strong association between PSC and inflammatory bowel disease (IBD). Other models of direct injury to biliary epithelia, peribiliary vascular endothelia or portal venous endothelia indicate that inflammation, chemokines and cytokines can produce diffuse sclerosis of bile ducts. Models of toxic, infectious or intra-luminal injury of the biliary tract also exhibit focal biliary sclerosis mediated by inflammation and cytokines. The histopathology of several models suggests a sequence of events beginning with secretion of proinflammatory cytokines by activated hepatic macrophages followed by peribiliary infiltration with CD4 and CD8 T cells with a T helper 1 phenotype. These results strongly suggest co-ordinated, pathogenetic roles for both the innate and adaptive immune responses. However, the stimuli that initiate and perpetuate peribiliary fibrosis remain unknown. Interestingly, several models are also associated with the development of anti-neutrophil cytoplasmic antibodies that react in a perinuclear and cytoplasmic pattern similar to that observed in patients with ulcerative colitis and/or PSC. Finally, models of extra-hepatic biliary obstruction continue to provide important information about the pathogenesis of portal fibrosis and secondary biliary cirrhosis that occurs in PSC and other diseases with obstruction of bile flow. Future studies in either existing or new animal models should advance our understanding of the pathogenesis of PSC, the major prerequisite for the development of effective therapies.
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PMID:Animal models for primary sclerosing cholangitis. 1149 70

Primary sclerosing cholangitis (PSC) is a chronic cholestatic and progressive disease, of unknown etiology, characterized by inflammation and fibrosis of intra-hepatic and extra-hepatic biliary tree. Two thirds of the patients have, simultaneously, ulcerative colitis (UC); on the other hand, PSC is the most common chronic hepatic disease in patients with inflammatory bowel disease (IBD). Patients who have both diseases simultaneously are prone to develop colorectal carcinoma and cholangiocarcinoma. The disease predominantly affects young men, may be asymptomatic or presented as fluctuating jaundice, pruritus and increased levels of the cholestasis biochemical markers, or as secondary billiary cirrhosis. The diagnostic gold standard are the cholangiographic abnormalities, consisting of multifocal stenosis and dilatations, involving both the intrahepatic and the extrahepatic biliary tree. Liver biopsy is useful only for staging the disease and to confirm the diagnosis, in the atypical forms. Ursodeoxycholic acid is a promising drug, nowadays, mainly in the first stages of the disease, in spite of doubtful efficacy. Combination therapy, using ursodeoxicolic acid, methotrexate and alternating antibiotics monthly may be sucessfull in PSC before bile strictures occur. Liver transplantation is the only life-saving therapeutic alternative, able to improve significantly the survival and the life quality of the patients.
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PMID:[PRIMARY SCLEROSING CHOLANGITIS] 1214 May 88

Cytosine guanine dinucleotide (CpG) island methylation is a known mechanism of epigenetic inheritance in postmeiotic cells. Through associated chromatin changes and silencing, such epigenetic states can influence cellular physiology and affect disease risk and severity. Our studies of CpG island methylation in normal colorectal mucosa revealed progressive age-related increases at multiple gene loci, suggesting genome-wide molecular alterations with potential to silence gene expression. However, there was considerable variation in the degree of methylation among individuals of comparable ages. Such variation could be related to genetic factors, lifestyle, or environmental exposures. Studies in ulcerative colitis and hepatocellular cirrhosis and neoplasia revealed that chronic inflammatory states are accompanied by marked increases in CpG island methylation in normal-appearing tissues, confirming the hypothesis that proinflammatory exposures could account for part of the epigenetic variation in human populations. Preliminary data also suggest potential influences of lifestyle and exposure factors on CpG island methylation. It is suggested that epigenetic variation related to aging, lifestyle, exposures and possibly genetic factors, is one of the modulators of acquired, age-related human diseases, including neoplasia.
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PMID:Epigenetic variation and human disease. 1216 98

Primary sclerosing cholangitis is a rare, cholestatic liver disease, most commonly affecting young men. The association of primary sclerosing cholangitis with other autoimmune disorders, although rare, indicates a genetic predisposition for this disease. We describe, for the first time, the association of primary sclerosing cholangitis, ulcerative colitis and coeliac disease in two sisters. Ulcerative colitis was mild and preceded liver disease in both patients. There were no symptoms of coeliac disease, and its silent form was diagnosed on the basis of serological tests. Both patients carried HLA molecules DR3 and DQ2. Although HLA DR4 was not found, there was a rapid progression of liver disease to cirrhosis and cholangiocarcinoma in one patient. The familial occurrence of primary sclerosing cholangitis, ulcerative colitis and coeliac disease supports the hypothesis of genetic predisposition for these diseases.
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PMID:Association of primary sclerosing cholangitis, ulcerative colitis and coeliac disease in female siblings. 1216 91

We report case of a peruvian patient with cirrhosis due to primary sclerosing cholangitis, associated with ulcerative colitis. The patient presented initially with intermittent diarrhea, manifesting features of chronic liver failure which progressed rapidly.Primary sclerosing cholangitis is a progressive diasease affecting intra and extrahepatic billary radicles, and is associated with ulcerative colitis in the majority of cases. The diagnosis is made by cholangiography, showing areas of stenosis, irregularity and dilatation of the biliary tree.In this article we report the clinical presentation and course of the patient, reviewing recent literature with emphasis in the association between primary sclerosing cholangitis and ulcerative colitis.
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PMID:[PRIMARY SCLEROSING CHOLANGITIS ASSOCIATED TO ULCERATIVECOLITIS AS A CAUSE OF CIRRHOSIS] 1220 10


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