Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic veno-occlusive disease (VOD) is the most common life threatening complication of preparative-regimen-related toxicity for bone marrow transplantation (BMT). The frequency of VOD varies greatly, from 1-2% in centers performing pediatric BMT for thalassemia to over 50% in some centers doing BMT for hematologic malignancy. The term liver toxicity syndrome is a clinicopathologic definition which encompasses the range of histopathology within the hepatic venules and surrounding sinusoids and hepatocytes. These histologic abnormalities are statistically associated with a clinical syndrome of jaundice, ascites, and painful hepatomegaly developing early post-transplant. Newer modalities which may aid accuracy are transvenous liver biopsy along with determination of the gradient between the wedged and free hepatic venous pressures, and measurement of blood coagulatory components, particularly protein C levels. Analyses of clinical risk factors for VOD are confounded by lack of a clear hierarchy of risk when comparing heterogeneous patient populations, the methods of patient selection and choice of controls, and whether analysis is univariate or multivariate. Prospective multivariate analyses indicate that the risk of developing liver toxicity is independently correlated with intensity of conditioning therapy, pre-transplant viral hepatitis, use of antimicrobial therapy with acyclovir, amphotericin, or vancomycin (reflecting fever), and mismatched or unrelated allogeneic marrow grafts. These analyses plus morphologic and biochemical data support the hypothesis that VOD is caused by cytoreductive injury to hepatocytes and endothelium in zone three of the liver acinus, and in turn strongly influenced by factors which induce the release of tumor necrosis factor-alpha (TNF-alpha) leading to enhancement or activation of coagulation with obstruction of hepatic sinusoids and venules. Pharmacokinetic measurements of busulfan as a conditioning agent demonstrate a correlation between high steady-state busulfan levels and liver toxicity and suggest that safer and/or more efficacious plasma busulfan concentrations can be obtained by making individual dose adjustments and by changing the schedule of administration. Conservative therapy of severe VOD, including the use of peritoneal-pleural shunts for relief of ascites, is unsatisfactory. Results from prophylactic studies aimed at preventing VOD by heparin or prostaglandin E1 indicate considerable differences with toxicity and efficacy. Use of the TNF-alpha blocker, pentoxifylline, has also shown promise in lessening VOD. A statistical model which predicts patients likely to have an unfavorable outcome from VOD has been used to select premorbid patients for promising new therapeutic modalities, such as recombinant tissue plasminogen activator.
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PMID:Hepatic veno-occlusive disease--liver toxicity syndrome after bone marrow transplantation. 142 75

Nonbacterial thrombotic endocarditis is an uncommon, but well-described, complication of bone marrow transplantation. We describe a case of nonbacterial thrombotic endocarditis following autologous bone marrow transplantation that was marked by weight gain, hepatomegaly, ascites, and extreme hyperbilirubinemia leading to a clinical diagnosis of hepatic veno-occlusive disease. Autopsy revealed nonbacterial thrombotic endocarditis of the tricuspid and pulmonic valves, and passive congestion of the liver, but there was no evidence of veno-occlusive disease. We discuss the pathophysiology and clinical features of nonbacterial thrombotic endocarditis and review its occurrence in association with bone marrow transplantation. Nonbacterial thrombotic endocarditis is often difficult to detect clinically and should be a diagnostic consideration in patients who develop systemic emboli or congestive heart failure after bone marrow transplantation.
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PMID:Nonbacterial thrombotic endocarditis clinically mimicking veno-occlusive disease of the liver complicating autologous bone marrow transplantation. 144 13

Hepatic veno-occlusive disease is a nonthrombotic obliteration of small intrahepatic veins by loose connective tissue. The venous occlusion may be progressive and lead to massive hepatocellular necrosis. Although originally described as a result of intoxication with plant alkaloids, it is now seen as a complication of high-dose antineoplastic chemotherapy, especially in the setting of bone marrow transplantation. The incidence of hepatic veno-occlusive disease after bone marrow transplantation approaches 20 percent, with mortality ranging from 7 to 50 percent. The clinical diagnosis may be quite accurate (as confirmed by biopsy or autopsy) and is based on the triad of jaundice, hepatomegaly and/or right upper quadrant pain, and ascites or unexplained weight gain. The pathogenesis is obscure but most likely relates to drug-induced venous endothelial damage. At the present time, therapy for veno-occlusive disease of the liver remains supportive. As intensive chemotherapy regimens (with or without bone marrow support) become more widely applied, it is expected that this disease will be encountered more frequently.
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PMID:Hepatic veno-occlusive disease. 352 87

Hepatic veno-occlusive disease (VOD) is a non-thrombotic obliteration of the lumina of small intrahepatic veins. VOD has been reported after exposure to a wide variety of pathogens. It has been suggested that the chemoradiotherapy used as the conditioning regimen for bone marrow transplant (BMT) is now the main cause of this disease. However, the pathogenesis of VOD after BMT is probably multifactorial. Endothelial injury of sinusoids and small hepatic veins is considered to be the initial event in genesis of VOD. This injury is followed by deposition of fibrin-related aggregates in the subendothelial zone. These aggregates, and the intramural entrapment of fluid and cellular debris, occlude progressively the hepatic venous outflow and generate a postsinusoidal intrahepatic hypertension. Clinically, VOD is characterized by jaundice, weight gain, ascites, painful hepatomegaly and platelet refractoriness developing early post transplant, although other posttransplant liver disturbances can produce a similar syndrome. VOD diagnosis is usually established by applying the clinical criteria proposed by the Seattle and Baltimore groups. When clinical diagnosis of VOD is uncertain, a transjugular liver study including a transvenous biopsy and measurement of the gradient between wedged and free hepatic venous pressure, is recommended in order to establish an accurate diagnosis. According to the literature data, the incidence of VOD ranges from 0 to 70% and its mortality from 20 to 50%. This very wide range is attributable to the different incidence of risk factors in the different series and to the differences in applying the diagnostic criteria.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatic veno-occlusive disease after bone marrow transplant. 846 32

Hepatic veno-occlusive disease (VOD), a common complication of bone marrow transplantation (BMT), is a result of intensive conditioning by chemo-radiotherapy. Endometrial injury causes fibrin deposition in the affected hepatic venules, leading to abnormal laboratory parameters followed by lethal full-blown disease. Previous studies have shown that unfractionated heparin can prevent VOD in BMT patients. Since low molecular weight heparin (LMWH) preserves the antithrombotic, but not the anticoagulant, activity of unfractionated heparin, we initiated a pilot study to determine the safety of LMWH for the prevention of VOD. Sixty-one patients undergoing BMT (allogeneic, n=24; autologous, n=37) were randomized to receive subcutaneous injection of enoxaparin (40 mg/day x 1) or a placebo prior to BMT conditioning and until day 40 after transplantation or discharge from the hospital. LMWH administration did not influence marrow engraftment, nor was it associated with bleeding tendency. Hemorrhagic events occurred significantly less frequently (P=0.025) were shorter duration (P=0.006) in the LMWH group than in the placebo group. Time to platelet recovery was significantly shorter (16.5 vs 29.6 days, (P=0.0075), and platelet transfusion requirements were lower (p=0.05) in the LMWH patients. VOD parameters occurred less frequently in the experimental group, including duration of elevated bilirubin levels (P=0.01) and incidence of hepatomegaly (P=0.04). LMWH, which seems to enhance platelet recovery, may be safely administrated to BMT patients in an attempt to prevent VOD of the liver.
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PMID:Low molecular weight heparin for the prevention of veno-occlusive disease of the liver in bone marrow transplantation patients. 862 87

Three children, treated with dactinomycin and vincristine without radiotherapy showed hepatic toxicity consistent with diagnostic criteria for hepatic veno-occlusive disease (VOD). Two patients were affected with Wilms' tumor and the third with malignant fibromatosis. The clinical manifestations of VOD were mild and regressed in all patients after supportive therapy. Serial ultrasonography (US) was performed in all cases and was useful in confirming the diagnosis and in evaluating the severity of the disease. US features of VOD were hepatomegaly, gallbladder wall thickening, ill-defined borders of the hepatic vessels, and ascites. Parenchymal heterogeneity was still present after several months as a result of the hepatic injury. The hazy appearance of the portal vessels and the gallbladder wall thickening seemed directly correlated with the degree of hepatic involvement in the early phase of VOD.
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PMID:Ultrasound in the management of hepatic veno-occlusive disease in three children treated with dactinomycin and vincristine. 894 Jul 35

In a study carried out in two hospitals in South Africa the authors identified 20 children suffering from hepatic veno-occlusive disease thought to be caused by the administration of traditional remedies. The predominant clinical presentation was ascites of various degrees and hepatomegaly. There was a high morbidity and mortality in the young infants, and in those cases who survived and were followed up the clinical pattern was one of progression to cirrhosis and portal hypertension. Pyrrolizidine alkaloid poisoning is one of the causes of the veno-occlusive disease. Therefore there is a need for objective confirmation of this. In four of our cases an on-admission urine specimen was available and in all of these a simple colorimetric screening test confirmed the presence of pyrrolizidine alkaloids. The other cases were admitted from peripheral hospitals and clinics and urine was not obtained until after 72 h, a time at which the levels of pyrrolizidines in urine were below the limit of sensitivity of the screening test. The screening method is helpful for the detection of acute ingestion of pyrrolizidines in large amounts, but is not sufficiently sensitive for the detection of chronic ingestion of smaller amounts. Nevertheless, in those patients who have hepatomegaly and ascites a positive finding of pyrrolizidines is important and may remove the necessity for expensive and invasive investigative measures.
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PMID:Clinical and analytical aspects of pyrrolizidine poisoning caused by South African traditional medicines. 1085 Mar 97

The clinical syndrome of hepatic veno-occlusive disease (VOD) is one of the most common and serious complications following hematopoietic stem cell transplantation (SCT). High-dose chemotherapy or chemoradiation therapy in the context of autologous and allogeneic SCT can profoundly injure sinusoidal endothelium and hepatocytes within zone 3 of the liver acinus, producing the clinical syndrome of hepatomegaly and/or right upper quadrant pain with jaundice and fluid retention, typically manifest as weight gain. The incidence is variable and ranges from 10 to 60%. Mild to moderate disease is characterized by eventual complete resolution. In contrast, severe disease frequently results in multiorgan failure and death. The purpose of this review is to discuss the pathophysiology and clinical features of VOD, and the current status and future directions of research for both prevention and treatment.
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PMID:Hepatic veno-occlusive disease following hematopoietic stem cell transplantation. 1154 78

Hepatic veno-occlusive disease (VOD) is a life-threatening complication after stem cell transplantation (SCT), characterized by thrombus formation in hepatic venules leading to a symptom triad of hyperbilirubinemia, hepatomegaly, and ascites. Multifactorial defects in the hemostatic system may contribute to its pathogenesis, but its remains to be investigated. Unusually large VWF multimers (UL-VWFMs), produced in and released from vascular endothelial cells, are most biologically active in the interaction with platelets under a high shear stress. UL-VWFMs are cleaved and degraded into smaller VWFMs by a specific liver producing plasma protease, termed VWF-cleaving protease (VWF-CPase), which has recently been identified as a metalloprotease solely produced in liver, termed ADAMTS13. Herein, we studied the correlation between plasma VWF-CPase activity and UL-VWFMs in 21 patients who received SCT, seven patients with VOD and 14 patients without VOD. In non-VOD patients, activities (mean +/- 1s.d.) of VWF-CPase were 78 +/- 17% of the control before the conditioning regimen, 76 +/- 18% on day 0, 64 +/- 19% on day 7, 57 +/- 23% on day 14, 68 +/- 13% on day 21 and 79 +/- 19% on day 28 after SCT. The respective values in VOD patients were 32 +/- 19%, 27 +/- 15%, 18 +/- 11%, 22 +/- 18%, 26 +/- 22% and 12 +/- 4%. Thus, VWF-CPase activity was significantly reduced in VOD patients, even before the conditioning regimen, and such a difference was not found in other laboratory tests. However, despite such a clear difference, UL-VWFMs were present in plasmas of both patient groups, together with the increase of VWF antigen and ristocetin cofactor activity. These results indicate that the measurement of this enzyme activity is extremely useful in predicting the occurrence of VOD prior to a demonstration of its direct involvement in its pathogenesis.
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PMID:Impaired activity of plasma von Willebrand factor-cleaving protease may predict the occurrence of hepatic veno-occlusive disease after stem cell transplantation. 1204 Apr 78

We report a previously healthy 29 years old man, presenting with a sudden episode of abdominal pain, mild jaundice, hepatomegaly and ascites. Magnetic resonance imaging study and liver biopsy were compatible with veno-occlusive disease. Incidentally, an ulcerative colitis and portal vein thrombosis were diagnosed. Anticoagulant treatment was started, with good clinical and radiological response. Veno-occlusive disease of the liver must be suspected In cases of liver failure and ascites associated to procoagulant conditions.
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PMID:[Hepatic veno-occlusive disease, idiopathic ulcerative colitis and portal thrombosis. Report of one case]. 1554 66


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