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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Advanced cirrhosis is known to be associated with extrahepatic organ dysfunction, but the mechanism for this cirrhosis complication is largely unknown. We measured tissue albumin leakage in rats with biliary cirrhosis or acute cholestasis and tested the hypothesis that arachidonic acid metabolites contribute to the vascular permeability change. Six weeks after bile duct ligation, rats with biliary cirrhosis exhibited increased extravascular leakage of 125I-albumin in lung (p < 0.001) and kidney (p < 0.01) but not in heart or brain. In contrast, in cholestatic rats 10 days after bile duct ligation, only the kidney albumin leak was significantly increased (p < 0.01). Tissue thromboxane B2 levels, measured with an enzyme immunoassay, were increased in lung, kidney and liver of cirrhotic and cholestatic rats. To determine whether thromboxane A2 contributes to the vascular permeability defects in cirrhosis, we pretreated cirrhotic rats with the thromboxane synthase inhibitor dazoxiben (10 mg/kg intraperitoneally every 8 hr) for 20 hr before assessment of vascular permeability. Dazoxiben blocked the increase in thromboxane B2 level in lung but not in kidney and lowered the lung but not the kidney albumin leak index. In cholestatic rats given a higher dose of dazoxiben (40 mg/kg intraperitoneally every 8 hr) for 20 hr, the kidney thromboxane B2 level but not albumin leak was significantly lowered. We conclude that chronic biliary obstruction in rats leads to increased vascular permeability in selected extrahepatic organs and that thromboxane A2 contributes to the vascular permeability increase in the lung. Whether thromboxane A2 plays a role in renal albumin leakage will require further study.
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PMID:Tissue eicosanoids and vascular permeability in rats with chronic biliary obstruction. 832 2

1. Curative treatment of hepatocellular carcinoma (HCC) depends on early diagnosis. 2. The cure rate for operable HCC occurring in the absence of cirrhosis is only 10% to 25%. 3. Features of HCC in patients with cirrhosis that are associated with a 5-year survival rate of 75% after liver transplantation include (1) solitary tumor less than 5 cm; (2) 3 or fewer tumors, each less than 3 cm; and (3) absence of vascular invasion. 4. Advanced cirrhosis limits the widespread application of partial hepatectomy to patients with HCC. 5. Neoadjuvant therapy has not yet been proven to improve patient outcome for early-stage HCC that is promptly treated by transplantation.
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PMID:Surgery and transplantation for hepatocellular cancer. 1108 80

Advanced cirrhosis is associated with generalized vasodilation of unknown origin, which contributes to mortality. Cirrhotic patients are endotoxemic, and activation of vascular cannabinoid CB1 receptors has been implicated in endotoxin-induced hypotension. Here we show that rats with biliary cirrhosis have low blood pressure, which is elevated by the CB1 receptor antagonist SR141716A. The low blood pressure of rats with CCl4-induced cirrhosis was similarly reversed by SR141716A, which also reduced the elevated mesenteric blood flow and portal pressure. Monocytes from cirrhotic but not control patients or rats elicited SR141716A-sensitive hypotension in normal recipient rats and showed significantly elevated levels of anandamide. Compared with non-cirrhotic controls, in cirrhotic human livers there was a three-fold increase in CB1 receptors on isolated vascular endothelial cells. These results implicate anandamide and vascular CB1 receptors in the vasodilated state in advanced cirrhosis and indicate a novel approach for its management.
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PMID:Endocannabinoids acting at vascular CB1 receptors mediate the vasodilated state in advanced liver cirrhosis. 1143 48

Advanced cirrhosis is associated with reduced platelet function and altered renal function and sodium handling. Arachidonic acid (AA) metabolites contribute to platelet aggregation and to maintain the response to diuretics in advanced cirrhosis. In the present study, we tested the effects of a dietary supplementation for 8 weeks with a triacylglycerol (triglyceride) enriched in AA (ARASCO; 4 g/day) or oleic acid (OA) on plasma and membrane fatty acid composition, platelet aggregation and renal prostaglandin (PG) metabolism. At baseline, all patients had reduced platelet aggregation. Patients treated with AA showed a significant increase in the percentage of AA in plasma lipids and membrane phospholipids. These changes were associated with an increased platelet aggregation in response to collagen (from 55.83 +/- 20.63 to 67.67 +/- 14.44%; P<0.05). At baseline, all urinary AA metabolites, including PGE2, 6-keto-PGF1alpha, 8-epi-PGF2alpha and 11-dehydro-thromboxane B2, were elevated in cirrhotic patients when compared with a group of normal subjects. After furosemide treatment, urinary excretion of 11-dehydro-thromboxane B2 increased significantly. Supplementation with AA did not result in any significant change in urinary PG excretion either before or after diuretic administration. The results of the present study show that dietary supplementation with AA effectively increases the levels of this fatty acid in plasma and membrane phospholipids and improves platelet aggregation. These data suggest a possible novel approach to the treatment of the haemostatic defect observed in these patients.
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PMID:Effects of dietary supplementation with arachidonic acid on platelet and renal function in patients with cirrhosis. 1287 51

We retrospectively reviewed 45 hip arthroplasties which were performed over a period of 20 years in 38 patients with cirrhosis of the liver. There was a high perioperative 30-day complication rate (26.7%). Advanced cirrhosis was associated with a higher risk of complications (p = 0.004) as also was increased age, a high level of creatinine, a low level of albumin, a low platelet count, ascites, encephalopathy and an increased operative blood loss. The survival of the prosthesis at five years was 77.8% and infection was a major cause of failure. In view of the high rate of early complications and the limited longevity of the prosthesis, surgeons who perform hip arthroplasty on such patients should counsel them appropriately preoperatively.
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PMID:Hip arthroplasty in patients with cirrhosis of the liver. 1293 97

Chronic liver diseases are amongst the top leading causes of death in Europe as well as in other areas of the world. Chronic liver diseases are characterized by unrelenting progression of liver inflammation and fibrosis over a prolonged period of time, usually more than 20 years, which may eventually lead to cirrhosis. Advanced cirrhosis leads to a complex syndrome of chronic liver failure which involves many different organs besides the liver, including the brain, heart and systemic circulation, adrenal glands, lungs, and kidneys. The high morbidity and mortality secondary to chronic liver failure is due to complications related to the dysfunction of these organs, either alone or, more frequently, in combination. Understanding the mechanisms leading to organ dysfunction is crucial to the development of strategies for treatment and prevention of complications of cirrhosis. This article reviews our current knowledge, as well as future perspectives, on the management of circulatory and renal dysfunction in chronic liver failure.
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PMID:Renal and circulatory dysfunction in cirrhosis: current management and future perspectives. 2085 Aug 87

Advanced cirrhosis is often complicated by a multi organ failure syndrome which involves many different organs besides the liver. The high morbidity and mortality secondary to this clinical setting is often related to renal dysfunction, either alone or, more frequently, in combination with other organ dysfunction. A clear definition of renal dysfunction, an accurate differential diagnostic process of its different phenotypes as well as of full understanding of its pathophysiological mechanisms are crucial to the development of strategies for the management of this complication. This article is based either on the more recent knowledge on renal dysfunction in advanced cirrhosis or current opinions among the members of the International Club of Ascites (ICA) on the management of this complication, obtained through a survey and discussed during the EASL-ICA Joint Meeting in Berlin in March 2011. It reviews critically our current knowledge and it outlines future perspectives, on the management of renal dysfunction in patients with cirrhosis.
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PMID:Current limits and future challenges in the management of renal dysfunction in patients with cirrhosis: report from the International Club of Ascites. 2250 81

Advanced cirrhosis is frequently associated with renal dysfunction. Hepatorenal syndrome (HRS) is characterized by the occurrence of kidney injury in cirrhotic patients in the absence of other identifiable causes. HRS is classified in 2 different types. Type 1 is characterized by acute renal failure and rapid functional deterioration of other organs, usually related to a precipitating event. Type 2 is characterized by slowly progressive renal failure and refractory ascites. Advanced liver disease induces the progression of hemodynamic alterations such as arterial vasodilation of splanchnic circulation and impairment of cardiac function. The resulting ineffective circulating blood volume promotes the activation of both the renin-angiotensin-aldosterone and sympathetic nervous system, by an increase of antidiuretic hormone activity, in an attempt to restore volemia. Despite fluid retention, ascites and dilutional hyponatremia, renal function is often initially preserved by renal production of vasodilators. However, further insults can lead to an imbalance between systemic vasoconstriction and local renal vasodilation, resulting in progressive renal failure. Over the last decade, clinical strategies to prevent HRS have been improved by a better understanding of the natural history of renal failure in cirrhosis, resulting in a reduction of HRS prevalence in cirrhotic patients. Vasoconstrictor drugs may improve renal function, but the effect on mortality has not yet been established. Vaptans, nonpeptide vasopressin receptor antagonists, may also reduce hyponatraemia and ascites, even if the clinical effects in HRS remain unknown. This review updates the pathophysiology, diagnosis and management of HRS.
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PMID:Pathophysiology, diagnosis and clinical management of hepatorenal syndrome: from classic to new drugs. 2467 26

Human serum albumin is a critical plasma protein produced by the liver with a number of accepted clinical indications in chronic liver disease including management of circulatory and renal dysfunction in patients with ascites. Advanced cirrhosis is characterised by reduced albumin concentration as well as impaired albumin function as a result of specific structural changes and oxidative damage. Traditionally, the biologic and therapeutic role of albumin in liver disease was attributed to its oncotic effects but it is now understood that albumin has a wide range of other important physiologic functions such as immunomodulation, endothelial stabilisation, antioxidant effects and binding multiple drugs, toxins and other molecules. This review discusses the multifunctional properties of albumin and, in particular, the biologic and clinical implications of structural and functional changes of albumin that are associated with cirrhosis. Based on these insights, we explore the current and potential future therapeutic uses of albumin in liver disease.
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PMID:Albumin in chronic liver disease: structure, functions and therapeutic implications. 2642 Feb 18

Approximately one-third of patients infected with chronic HCV have cirrhosis, and this is likely to increase in the near future. The risk of complications, mainly the development of hepatocellular carcinoma, depends on the presence of cirrhosis, and a significant increase in the incidence of cirrhosis-related events, including mortality, is likely in the following years. All-oral therapy with direct-acting antivirals (DAAs) offers a safe and short treatment, with cure rates over 90% in compensated cirrhosis. Cirrhotic patients should be given high priority for treatment because viral clearance has a significant impact on the natural history of HCV infection, halting the progression of the disease and inducing the regression of fibrosis, as well as reducing the need for liver transplantation and improving survival. The benefit of DAAs is great in patients with decompensated cirrhosis, up until recently a population for whom no alternative therapy was available. The efficacy of all-oral therapy has been reported to improve liver function in about 50% of Child-Pugh class C patients. The regression of cirrhosis observed in more than half of patients achieving viral eradication on prior interferon-based regimens still has to be demonstrated in patients treated with DAAs, although there is reason to believe that this will happen. Advanced cirrhosis will eventually become the last boundary of antiviral therapy that will soon be conquered with new drugs currently pending approval.
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PMID:Why is viral eradication so important in patients with HCV-related cirrhosis? 2755 73


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