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

The pathogenesis of veno-occlusive disease (VOD) of the liver appears to be secondary to endothelial damage of terminal hepatic venules, which leads to activation of the coagulation cascade, fibrin deposition, and eventual fibrous obliteration of the hepatic venules. Patients with VOD usually present with jaundice, hepatomegaly, weight gain, and ascites. This complication is usually associated with a high mortality rate. We report here the frequency and treatment of VOD in our autologous bone marrow transplant (BMT) patient population. Three of 15 (20%) children (median age 9 years) developed VOD and were treated with recombinant tissue plasminogen activator (rt-PA). Two of these three patients were prepared for BMT with busulfan (16 mg/kg) and cyclophosphamide (Cytoxan, 200 mg/kg), while the other child received cytosine arabinoside (ARA-C 18 g/m2), Cytoxan (3,600 mg/m2) and total body irradiation (TBI, 1,400 y). VOD developed between days 7-24 posttransplant. Clotting studies obtained pretransplant and during VOD included prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, fibrin-degradation product (FDP), proteins C and S, and platelet count. There was no correlation between the incidence of VOD and coagulation status. All patients had normal pretransplant clotting studies. However, protein C levels were noted to be consistently low for those patients at the time of VOD. All three patients received rt-PA at a dose of 0.25-0.5 mg/kg for 4 days. This dose produced increased levels of FDP but did not significantly prolong PT nor PTT. Two of the patients had dramatic responses and had complete resolution of VOD within 6-12 days from the start of therapy. The other patient died of fulminant hepatic failure. It seems that rt-PA is effective in VOD of the liver, which may be associated with low protein C level.
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PMID:Recombinant tissue plasminogen activator (rt-PA) for veno-occlusive liver disease in pediatric autologous bone marrow transplant patients. 819 48

Budd-Chiari syndrome is a rather unusual clinical situation caused by occlusion of the hepatic vein of inferior vena cava, the classical triad of which are abdominal pain, ascites and hepatomegaly. A 29-year-old gravida 3 para 1 woman delivered an immature male baby weighing 2172 g with an Apgar score of 9 points at 35 weeks and 3 days of gestation. She was transferred to the National Hospital Organization Osaka National Hospital 112 days after delivery due to the sudden development of massive ascites. Magnetic resonance angiography and enhanced computed tomography detected the occlusion by thrombosis of both the middle and left hepatic veins, so she was diagnosed with Budd-Chiari syndrome. Her protein C antigen and activity were 37% and 50%, respectively, corresponding to type 1 protein C deficiency. Conservative treatment by continuous oral treatment of spironolactone (25 mg/day), furosemide (20 mg/day) and prophylactic warfarin (2 mg/day) much improved the ascites.
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PMID:Case of Budd-Chiari syndrome 3 months after vaginal delivery. 1884 Jan 63