Cholestatic syndrome

The possibility of defining serum BA composition was also assessed in the reported study. Analysis of the free fraction before and after treatment with ampicillin of a patient with PBC was performed (Fig. 5.4.9). The antibiotics are used in the therapy of cholestatic syndrome, but some studies have been carried out to define their use. This kind of therapy inhibits the production of secondary BAs (DCA and LCA) and the deconjugation of taurine and glycine conjugates. Consequently, an... 

Detection of biliary obstruction, such as in cholestatic syndrome with and without jaundice... 

Trauner, M, Boyer, J.L. Cholestatic syndromes. Curr. Opin. Gastroenterol. 2003 19 216-231... 

A severe cholestatic syndrome (H. Ballard et al., 1961) can be observed in patients suffering from alcoholic fatty liver, (s. fig. 28.16) The clinical picture may correspond to that of obstructive jaundice and cause great problems in differential diagnosis, particularly because such patients may not have been known before to be suffering from alcohol-induced liver disease. Extremely severe forms to the point of acute liver failure have been observed. 

Trauner M, Boyer JL. Cholestatic syndromes. Curr Opin Gastroenterol 2001 I7 242-56. 

Although such purely hepatitic and cholestatic syndromes are recognizable, the clinical picture in individual patients may not be clear cut. Furthermore, there are many agents that tend to produce mixed effects. Representative hepatotoxins from each group are presented in Table 10. 

Trauner, M., Fickert, P., and Wagner, M. (2007) MDR3 (ABCB4) defects a paradigm for the genetics of adult cholestatic syndromes. Semin. Liver Dis. 27, 77-98. 

With the exception of genetically impaired individuals with Menkes disease and Wilson s disease, individuals who suffer from various grossly inadequate diets, diarrhea and severe malnutrition, and the patients who suffer from primary biliary cirrhosis, and cholestatic syndromes of Indian childhood cirrhosis, the development of copper deficiency and toxicity is not a significant risk for man. 

Hepatic copper > 250 p g dry weight Due to regional variation - In pts with active Uver disease - In pts with regenerative nodules Cholestatic syndromes... 

As mentioned previously, patients with hepatic sarcoidosis may develop a chronic cholestatic syndrome with jaundice, fever, malaise, anorexia, weight loss, pruritus, and a cholestatic pattern of abnormal Uver function tests (77-79). These symptoms are often severe and require treatment. Prednisone in doses of 30 to 60 mg/day may improve symptoms, lower serum alkaline phosphatase levels, and improve hepatomegaly (77,96). Ursodeoxycholic acid, which inhibits intestinal absorption and increases biliary secretion of cholic and chenodeoxycholic acids (97), is often effective for the cholestatic syndrome of hepatic sarcoidosis (98,99). A dose of 10 mg/kg/day has been recommended (98,99). 

There is very little evidence relating to the role of ROMs in cholestatic liver disease. Serum selenium and glutathione peroxidase activity are decreased in humans with intrahepatic cholestasis of pregnancy (Kauppila et al., 1987). Low levels of vitamin E have been reported in patients with primary biliary cirrhosis, and in children with Alagille s syndrome or biliary atresia (Knight et al., 1986 Jeffrey etal., 1987 Lemonnier etal., 1987 Babin etal., 1988 Kaplan et al., 1988 Sokol etal., 1989). Serum levels of Mn-SOD are increased in patients with all stages of primary biliary cirrhosis compared with patients with other forms of chronic liver disease, although whether this causes or results from the disease process is unclear (Ono etal., 1991). 

Adverse effects that are not unequivocally related to inhibition of prostaglandin synthesis include hepatic effects (hepatitis, hepatic necrosis, cholestatic jaundice, increased serum aminotransferases), dermal effects (photosensitivities, Stevens-Johnson syndrome, toxic epidermal necrolysis, onycholysis), central nervous system (CNS) effects (headaches, dizziness, tinnitus, deafness, drowsiness, confusion, nervousness, increased sweating, aseptic meningitis), ocular effects (toxic amblyopia, retinal disturbances), and certain renal effects (acute interstitial nephritis, acute papillary necrosis). 

Signs and symptoms of gold toxicity, the primary serious reaction, include decreased Hgb level, decreased granulocyte count (less than 150,000/mm ), proteinuria, hematuria, stomatitis, blood dyscrasias (anemia, leukopenia WBC count less than 4000/mm, thrombocytopenia, and eosinophilia), glomerulonephritis, nephrotic syndrome, and cholestatic jaundice. 

Serious reactions such as blood dyscrasias, agranulocytosis, leukocytopenia, thrombocytopenia, cholestatic jaundice, neuroleptic malignant syndrome (NMS), constipation or paralytic ileus, priapism, QT prolongation and torsades de pointes, seizure, systemic lupus erythematosusdike syndrome, and temperature regulation dysfunction (heatstroke or hypothermia) occur rarely. 

Extrapyramidal reactions include parkinsonism, acute muscular dystonias, akathisia, tardive dyskinesia and malignant neuroleptic syndrome. They can also cause hypersensitivity reaction including cholestatic jaundice, skin rash, urticaria, photosensitivity and contact dermatitis. There is also blue pigmentation of skin, lenticular opacities on prolonged use of drug. 

Among the more severe adverse reactions, Stevens-Johnson epidermal necrolysis syndrome, thrombocytopenia, agranulocytosis, and nephrotic syndrome have all been observed. Like diclofenac, sulindac may have some propensity to cause elevation of serum aminotransferases it is also sometimes associated with cholestatic liver damage, which disappears when the drug is stopped. 

Hepatic granulomas have been reported as a hypersensitivity reaction to chlorpropamide (101). Cholestatic jaundice from sulfonylureas is also probably of allergic origin it is rare and has been described with glibencla-mide (102), also in combination with hepatorenal syndrome (103), acetohexamide (104), chlorpropamide (105), gliclazide (106), and tolazamide (107). 

A 67-year-old man developed Stevens-Johnson syndrome after taking glibenclamide 20 mg/day for 4 weeks, having previously used insulin. He died from hemorrhagic bronchopneumonia. Post mortem examination also showed features of granulomatous arteritis and cholestatic interface hepatitis, suggestive of a hypersensitivity reaction (129). 

Cholestatic hepatitis developed in a 71-year-old man with nephrotic syndrome (2). Hepatic function was normal after several months of fluvastatin 20 mg/day. Some weeks after the dose was increased to 40 mg/day, his gamma-glutamyl transpeptidase activity rose from normal to 1818 IU/1, with negative serology for viruses. After normalization, re-introduction of fluvastatin 20 mg/day was not tolerated, but he did tolerate simvastatin 20 mg/day. 

Cholestatic Alagille s syndrome Progressive familial intrahepatic cholestasis... 

Patients with cholestatic conditions such as gallstones, primary sclerosing cholangitis or Alagille s syndrome often suffer from pruritus that can be extremely debilitating. In such patients it would seem sensible to avoid medication that could exacerbate this symptom. Administration of opiates via the intrathecal and epidural routes lead to a high incidence of pruritus (up to 80% with epidural morphine) [2]. 

Oestrogen receptors are found in liver tissue, and consequently the high levels of oestrogens contained in COCs that travel to the liver on first pass from the portal circulation may account for the number of hepatic complications associated with these preparations, e.g. cholestatic jaundice, hepatocellular carcinoma, Budd-Chiari syndrome [2]. 

Adverse hepatic effects have been linked to the use of oral contraceptives, including hepatic dysfunction, cholestatic jaundice, benign hepatic tumours and peliosis hepatis. In addition, oral contraceptives have a number of less common but important effects on the liver. A correlation between the development of the Budd-Chiari syndrome and COCs has been described, and progestational derivatives have been linked to exacerbations of hepatic porphyria [12]. 

Cholangiodestmctive cholestasis is caused by bile duct obstruction which may be intrahepatic or extrahepatic. Bile duct injury may lead to sloughing of epithelial cells into the lumen, cell edema, and inflammation, which may contribute to obstruction (Treinen-Moslen, 2001 Plumlee, 2004). Chronic lesions associated with cholangiodestmctive cholestasis typically include bile duct prohferation and periductular fibrosis. Vanishing bile duct syndrome, characterized by a loss of bile ducts, has been seen in chronic cholestatic disease in humans (Zimmerman, 1999 Treinen-Moslen, 2001) and has been produced experimentally in dogs (Uchida, 1989). 

The thionamide drugs are all liable to cause minor and major adverse effects. Minor are rash, urticaria, arthralgia, fever, anorexia, nausea, abnormalities of taste and smell. Major are agranulocytosis, thrombocytopenia, acute hepatic necrosis, cholestatic hepatitis, lupus-like syndrome, vasculitis. 

This virus species derived its name from the town of Coxsackie in the state of New York, where virological evidence thereof was successfully obtained for the first time. Coxsackie viruses are assigned to the picornavirus group, consisting at present of 23 A and 6 B types. Coxsackie hepatitis with mesenchymal reactions, portal infiltration and focal hepatocellular necrosis sometimes occurs, especially in infants. Cholestatic, predominantly centrolobular forms of the disease, can develop in adults. A lethal course is extremely rare. (66-68) The course of infection with the Coxsackie type B4 or B5 virus may give rise to the Fitz-Hugh-Curtis syndrome with the development of the typical violin string-like adhesive strands. (65) (s. fig. 24.2)... 

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