Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypercholesterolemia is commonly associated with primary biliary cirrhosis. In the general population, elevated serum cholesterol is associated with an increased risk of atherosclerosis. The relative risk has been poorly defined in primary biliary cirrhosis patients with hyperlipidemia. In addition, the hyperlipidemic state seen with primary biliary cirrhosis has not been well studied. We prospectively observed 312 patients with primary biliary cirrhosis for a median of 7.4 yr. During this period, 128 patients died. The incidence of atherosclerotic death in patients with primary biliary cirrhosis was not statistically different when compared with an age-matched and sex-matched U.S. control population. A similar group of 50 consecutive PBC patients had detailed serum lipid profiles. Findings included progressive increases in total cholesterol and low-density lipoprotein cholesterol with an increasing histological stage or severity of disease. High-density lipoprotein cholesterol was elevated in all stages, with the highest levels in histological stage 2 and 3 disease. Triglycerides were normal or slightly elevated in all stages. Apoprotein A-I was elevated in all but histological stage 4 disease. Our study suggests the hyperlipidemia associated with primary biliary cirrhosis does not place these patients at risk for atherosclerotic death. In light of the limitations imposed by our relatively small sample size, however, additional patients should be studied. Furthermore, an examination of the pathophysiological mechanisms leading to hypercholesterolemia should be the topic of further study.
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PMID:Hypercholesterolemia and atherosclerosis in primary biliary cirrhosis: what is the risk? 156 27

Hyperlipidemia is a common complication of PBC. Ten patients with serologically and histologically defined PBC were randomized to receive either oral cyclosporin A (CyA) or placebo for one year. Fasting blood samples were obtained from subjects at the beginning, and following one year of treatment, for plasma lipids, apolipoproteins AI (apo AI) and B (apo B), and lecithin-cholesterol acyltransferase (LCAT) activity. On entry to the study there were no significant differences between groups for serum concentrations of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), free cholesterol (FC), total phospholipids (TPL), apo AI, apo B and LCAT activity. Compared to normal laboratory values, baseline TC was elevated in 5/10, LDL-C in 5/10, TPL in 6/10, while LCAT activity was decreased in 8/10 patients. The percent change after one year for CyA group vs the placebo group are as follows: total cholesterol, -22 vs -8%; LDL cholesterol -33 vs -25%; free cholesterol, -39 vs -14%; total phospholipids, -46 vs -23%; and LCAT activity, +/- 236 vs +/- 43%. The decrease in TC, LDL-C, FC, TPL with increase in LCAT activity suggests that CyA administration is associated with improvement in the lipid abnormalities of PBC.
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PMID:Effect of cyclosporin A on serum lipids in primary biliary cirrhosis patients. 261 91

Cholestasis may be extrahepatic or intrahepatic in origin. The block in bile secretion may be complete or incomplete to variable extent. Complete cholestasis occurs in case of primary parenchymal disease (intrahepatic cholestasis) or total obstruction of extrahepatic bile ducts (extrahepatic cholestasis). Incomplete block in bile secretion is due to incomplete obstruction of intra- or extrahepatic bile ducts (intra- or extrahepatic cholestasis or both). Histologically, it is useful to distinguish between bilirubionstasis and cholate-stasis. Complete secretory block causes as early changers: bilirubinostasis (in hepatocytes, canaliculi and Kupffer cells) in acinar zone 3, and "ductular reaction" in acinar zone 1. The latter refers to an increase in periportal ductular profiles, associated with neutrophil infiltration. With longer duration of cholestasis, further lesions ensue: feathery degeneration of hepatocytes due to retention of detergent bile acids, cholestatic liver cell rosettes representing a shift from hepatocellular to biliary differentiation, xanthomatous cells reflecting hyperlipidemia, cholate stasis in acinar zone 1 due to overload of membrane-damaging bile acids, eventually paraportal bile infarcts, and progressive ductular reaction. The latter may be due to multiplication of pre-existing ductules, to metaplasia of periportal hepatocytes, or to activation of progenitor cells. It is invariably associated with periductular fibrosis: the pacemaker for increasing matrix deposition, resulting in biliary fibrosis and eventually in true biliary cirrhosis. Incomplete cholestasis (e.g. PBC, PSC) is characterized by absence of bilirubinostasis during long periods of time, whereas the afore mentioned features of chronic cholestasis do appear. Hence follows that the most reliable markers of chronic incomplete cholestasis are cholate stasis, cholestatic rosettes and ductular reaction. Bilirubinostasis is only a late and often ominous sign.
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PMID:Histopathology of cholestasis. 860 Jun 86

Osteoporosis is several times more common in patients with PBC compared with the general population. Maintaining adequate intake of calcium and vitamin D is important for prevention of bone loss. The use of bisphosphonates or vitamin K to improve bone mineral density in osteopenic patients seems promising and needs to be further evaluated. Patients with PBC may develop fat-soluble vitamin deficiencies, especially vitamins A and D; serum levels should be investigated in patients considered at risk with the aim of recommending appropriate replacement therapy. Finally, hyperlipidemia in PBC does not seem to be associated with an increased risk of atherogenesis. New therapies in this patient population are currently under investigation.
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PMID:Management of osteoporosis, fat-soluble vitamin deficiencies, and hyperlipidemia in primary biliary cirrhosis. 1459 36

Despite near universal use of ursodeoxycholic acid (UDCA) several patients with PBC still progress to liver transplant (LT) or death. Pruritus and fatigue are the most common symptoms. Liver transplantation for pruritus is highly effective but fatigue will not disappear in the majority of the patients. In contrast to other liver diseases, portal hypertension may develop in pre-cirrhotic patients with PBC. Patients with PBC have an incidence rate of 3.4 hepatocellular carcinoma cases for every 1000 patient-years and risk factors are advanced stage of the disease and male sex. For the appropriate timing of LT the utility of prognostic models (bilirubin, Mayo risk score and MELD, in particular) and standard exception points in case of HCC are established. However, recent data from different part of the world demonstrated that PBC patients compared to patients with PSC have higher waiting-list mortality. Hyperlipidemia can be present in up to 80% of the patients but there is no evidence for an elevated cardiovascular risk, certainly not in relationship with LT. Patients transplanted for PBC suffer more frequently from acute cellular and also late cellular rejection. However, 5-year patient survival rates after LT of 80-85% is better than for most other indications. Recurrent PBC is reported in a range from 14% up to 42% after LT but in contrast to other autoimmune diseases graft loss due to recurrent disease is not a major issue. The type of immunosuppression after LT was found to be associated with the incidence of recurrence but since mediate-term impact on overall and graft survival is negligible, tacrolimus-based regimens remain standard at most centers. Observational studies suggest that long-term administration of UDCA following LT has a beneficial effect on recurrence of PBC. Therefore biomarkers after LT that may identify patients at risk for recurrence should be further explored to allows early medical intervention.
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PMID:PBC-transplantation and disease recurrence. 3034 4