Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0008370 (cholestasis)
 9,378 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pruritus and fatigue are the most common symptoms of patients with PBC, and both have marked negative impact on quality of life. Over the past decade, evidence has emerged supporting a role of the central nervous system in the pathogenesis of these two common manifestations of PBC. There is no evidence that the pruritus of cholestasis is mediated in the skin. Clinical and laboratory data do support a role of the opioid neurotransmitter system in the mediation of the pruritus of cholestasis; a central mechanism has been proposed. Treatment with opiate antagonist is thus a specific alternative. Studies of the behavioral consequence of the pruritus of cholestasis, scratching activity, allow for the design of clinical trials with objective end-points. The etiology of fatigue is unknown. A central component is being considered. The identification of objective alterations in fatigue and the adoption of a definition that incorporates the perception and the behavioral consequences of fatigue should facilitate the development of objective methodology. The potential role of various neurotransmitter systems, including the serotonin system and the opioid system, in the mediation of the fatigue of PBC seems to merit further investigation.
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PMID:Pruritus and fatigue in primary biliary cirrhosis. 1459 35

Primary biliary cirrhosis (PBC) is an autoimmune liver disease of unknown etiology resulting in the progressive destruction of the intrahepatic bile ducts and leading to chronic cholestasis and ultimately liver cirrhosis and failure. The immune response in PBC seems to be mediated by autoantibodies as well as autoreactive T lymphocytes directed against mitochondrial antigens in biliary epithelial cells, primarily PDC-E2. Experimental evidence suggests a role of the hormone/cytokine leptin in autoimmune diseases. Leptin is an adipocyte-derived molecule that acts as a hormone influencing food intake and energy metabolism as well as a cytokine with pro-inflammatory, immune-regulatory functions. To study serum leptin in PBC and its association with disease severity, we evaluated serum levels in 37 patients with PBC (27 with no signs of fibrosis or cirrhosis at histologic examination) and 37 age- and sex-matched healthy controls using a validated ELISA method. We found that patients with PBC had significantly lower leptin serum levels compared with healthy controls (13.6 +/- 13.8 vs. 17.6 +/- 11.6; P < 0.05). No correlation between disease severity and serum leptin levels was found. This study has demonstrated that leptin levels are decreased in the serum of patients with PBC but do not seem to be associated with disease severity. Data do not seem to indicate a direct role of leptin in the perpetuation of the autoimmune response in PBC. However, further studies are warranted to further characterize the functions of leptin during the natural history of autoimmunity.
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PMID:Decreased serum leptin levels in primary biliary cirrhosis: a link between metabolism and autoimmunity? 1612 61

Inflammatory disorders of the biliary tract present difficult diagnostic problems in liver needle biopsies. The aim of this study was to perform a detailed histologic analysis of liver biopsies from patients with biliary tract disorders, classify them by pattern of inflammation, and determine the accuracy of the histologic classification by clinical follow-up. Percutaneous liver needle biopsies from the surgical pathology files of UmassMemorial Healthcare (UMMHC) from 2000 to 2003 with a diagnosis suggesting a biliary tract process (n = 32) and four biopsies from cases with systemic non-biliary tract disorders were analyzed for multiple histologic features and classified as one of five patterns: acute cholangitis/pericholangitis (ACP), lymphocytic cholangitis (LC), granulomatous (G), ductopenia (D), or non-specific (NS). When compared to the "gold standard" diagnosis based on all clinical data, the concordance between the histologic classification and the clinical diagnosis was: 50% for ACP and bile duct obstruction; 77% for LC and immune-mediated cholangitis NOS; 100% for G and G cholangitis; 100% for D and idiopathic adulthood D; and 50% for NS and non-biliary tract disorders. Our findings suggest that classifying biopsies by pattern of injury is helpful in guiding the subsequent clinical work-up. ACP pattern correlates with bile duct obstruction, infection, and ischemia. LC correlates with serologic studies supporting immune-mediated processes. G pattern suggests further work-up for PBC, drug, tuberculosis, or sarcoidosis. D pattern establishes the clinical diagnosis. NS pattern includes cases of primary sclerosing cholangitis, which cannot be diagnosed by biopsy alone.
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PMID:Cholangitis: a histologic classification based on patterns of injury in liver biopsies. 1625 9

Primary biliary cirrhosis is a chronic liver disease of unknown etiology, characterized by inflammation and destruction of the intrahepatic biliary ducts, resulting in chronic cholestasis and eventually cirrhosis. The main clinical manifestations consists of pruritus, jaundice, xanthomas, and the consequences of intestinal malabsorption, including vitamin deficiencies and osteodystrophy. Treatment of PBC is addressed at preventing or relieving the symptoms and clinical consequences of chronic cholestasis, and also at correcting the bile duct abnormalities by specific treatments. Pruritus is treated with cholestyramine, but in some cases other drugs, such as rifampicin or opioid antagonists are needed. Bisphosphanates are effective for increasing bone mass in osteopenic patients. Vitamin D and cAlcium supplements are also recommended, particularly in patients with severe cholestasis. Ursodeoxycholic acid (UDCA) has become the standard treatment (13-15 mg/kg/day), resulting in marked relieving of cholestasis. UDCA also prevents the histological progression of the disease, although the effects on survival are less apparent. Small trials of combination therapy using UDCA with methotrexate, colchicine, or prednisone, have been reported but have not shown any increased efficacy over UDCA therapy. Liver transplantation is the only treatment available when cholestasis progresses, with very good survival rates.
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PMID:Treatment of primary biliary cirrhosis. 1649 78

Liver function tests include biochemical parameters (AST, ALT, GGT or Alkaline phosphatase), bilirubin and albumin levels and coagulation tests as prothrombin activity. These tests are commonly used in the routine screening even in symptomatic as in asymptomatic patients, and the right evaluation of the results is of vital importance. Cytolytic elevation in serum aminotransferases: In mild chronic elevation pharmacological toxicity, viral hepatitis, alcoholic and non-alcoholic fatty liver disease and hemochromatosis, should be excluded. Cholestatic elevation os serum enzymes: The first option should be to establish the origin of the alkaline phosphatase elevation, with the evaluation of the GGT levels to confirm the hepatic origin. The next step should be to distinguish the presence of an extrahepatic (biliary obstruction) or intrahepatic (PBC, PSC, drugs, etc) cholestasis, in these cases the most important test should be the abdominal ultrasound, in order to evaluate the biliary system. Hyperbilirubinemia: Non conjugated hyperbilirubinemia (hemolysis, ineffective erythropoiesis, Gilbert or Criggler-Najjar syndromes) and conjugated hyperbilirubinemia, an unusual situation in which Rotor and Dubin-Johnson Syndromes should be considered. The evaluation of albumin and prothrombin levels evaluates the hepatic function per se, allowing to differentiate between acute and chronic diseases. At present, there are not prospective studies to evaluate the efficacy of the liver function tests. To carry out a complete medical history, an appropriate physical examination and the appropriate application of non-invasive diagnostic tests (serology, iron levels, autoimmunity or abdominal ultrasound) allow to perform a right diagnosis in most patients, making more complex tests, including liver biopsy, secondary.
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PMID:[Utility of analytical parameters in the diagnosis of liver disease]. 1737 60

A 75 year old patient was admitted to hospital due to painless jaundice and fatigue. Patient's history was not remarkable for chronic viral hepatitis, autoimmune hepatitis, hereditary metabolic disorders or a hepatotoxic damage. Laboratory tests revealed significant elevation of the parameters of cholestasis and aminotransferase activity, a significantly elevated titer of both antinuclear (ANA) and antimitochondrial (AMA) antibodies. Abdominal ultrasound and computertomography showed no mechanic cholestasis nor tumorous process but a situs inversus abdominalis of the abdominal parenchymatous organs. Portal and periportal inflammation, consistent with autoimmune hepatitis, was diagnosed histologically after performing laparoscopic liver biopsy. Regarding the significantly elevated cholestatic parameters and the positive AMA-autoantibodies AIH-PBC overlap syndrome was highly probable so medical treatment including both ursodeoxycholic acid and immunosuppressive therapy with corticosteroids and azathioprine was started resulting in a continous downward tendency of liver enzymes and an improvement of the patient's clinical condition. Finding the correct diagnosis and therapy of autoimmune liver disease is not always easy and unproblematic. Regarding its sometimes fatal progression and good response towards medical treatment prompt diagnosis and institution of autoimmune hepatitis--alone or combined as PBC/AIH overlap syndrome--should not be deferred. Laparoscopic liver biopsy should be the method of choice in patients's with situs inversus abdominalis regading the variable anatomy.
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PMID:[Cholestatic hepatitis in situs inversus abdominalis]. 1763 66

New insights into the molecular mechanisms of bile formation and cholestasis have provided new concepts for pharmacotherapy of cholestatic liver diseases. The major aim in all forms of cholestasis is the reduction of hepatocellular retention of bile acids and other potentially toxic constituents of bile. Reduction of hepatocellular retention may be achieved by drugs that stimulate hepatocellular secretion via the canalicular route into the bile or via the alternative route across the basolateral membrane into the blood, and by drugs that stimulate the hepatocellular metabolism of hydrophobic bile acids to hydrophilic, less toxic metabolites. In cholestatic liver diseases that start with an injury of the biliary epithelium (e.g., primary biliary cirrhosis; PBC), protection of the cholangiocytes against the toxic effects of hydrophobic bile acids is most important. When hepatocellular retention of bile acids has occurred, the inhibition of bile acid-induced apoptosis becomes another target of therapy. Ursodeoxycholic acid protects the biliary epithelium by reducing the toxicity of bile, stimulates hepatobiliary secretion by upregulating transporters and inhibits apoptosis. It is the mainstay of therapy in PBC but of benefit also in a number of other cholestatic liver diseases. New drugs such as 6-ethyl-chenodeoxycholic acid and 24-nor-ursodeoxycholic acid are being evaluated for the treatment of cholestatic liver diseases.
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PMID:Pharmacotherapy of cholestatic liver diseases. 2057 15

The care of the patient with cholestasis hinges on identifying the etiology, treating reversible causes, and managing chronic cholestatic processes. PBC and PSC are important causes of chronic cholestasis, and are the most common causes of cholestatic liver disease. Effective therapy is available for patients with PBC, whereas none exists for patients with PSC. Awareness of the complications that may be associated with cholestasis and implementing the appropriate management are essential.
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PMID:Cholestatic liver disease. 2426 15

Primary biliary cirrhosis with autoimmune hepatitis (PCB/AIH) overlap is characterized by uncertain behavior and no standardized treatment. A 35 year-old-woman with vitiligo, jaundice and cholestasis fulfilled serological, biochemical and histological criteria for PBC/AIH overlap. Treatment was initiated with conventional doses of corticosteroid and ursodeoxycholic acid. Her condition worsened with poor biochemical hepatic response. The course of action was altered to institute high doses of ursodiol, azathioprine and corticosteroids for extended periods of time. This case illustrates how increased understanding of the overlap PBC/AIH leads to new interventions. Recognition of these variant forms is critical for institutional management of both disease entities.
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PMID:Vitiligo, jaundice and cholestasis in a middle aged woman: a case report. 2506 50

Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by the destruction of interlobular biliary ductules, which progressively leads to cholestasis, hepatic fibrosis, cirrhosis, and eventually liver failure. Several mouse models have been used to clarify the pathogenesis of PBC and are generally considered reflective of an autoimmune cholangitis. Most models focus on issues of molecular mimicry between the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), the major mitochondrial autoantigen of PBC and xenobiotic cross reactive chemicals. None have focused on the classic models of breaking tolerance, namely immunization with self-tissue. Here, we report a novel mouse model of autoimmune cholangitis via immunization with syngeneic bile duct protein (BDP). Our results demonstrate that syngeneic bile duct antigens efficiently break immune tolerance of recipient mice, capturing several key features of PBC, including liver-specific inflammation focused on portal tract areas, increased number and activation state of CD4 and CD8 T cells in the liver and spleen. Furthermore, the germinal center (GC) responses in the spleen were more enhanced in our mouse model. Finally, these mice were 100% positive for anti-mitochondrial antibodies (AMAs). In conclusion, we developed a novel mouse model of PBC that may help to elucidate the detailed mechanism of this complex disease.
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PMID:A Mouse Model of Autoimmune Cholangitis via Syngeneic Bile Duct Protein Immunization. 2912 60


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