Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ursodiol is a hydrophilic, non-hepatotoxic bile salt indicated for the medical treatment of cholesterol gallstones. This pilot study explored the use of prophylactic ursodiol in an attempt to decrease the incidence and severity of veno-occlusive disease (VOD) of the liver following allogeneic bone marrow transplantation (BMT). Between February 1991 and January 1992, 22 consecutive patients undergoing BMT for hematologic malignancies received the BU(4)/CY(2) preparative regimen and CSA/MTX for GVHD prophylaxis. Ursodiol, 600-900 mg daily by mouth was begun at least 1 day prior to beginning the preparative regimen. Results for this pilot group were compared to a control group of 28 consecutive patients transplanted between June 1989 and January 1991 with the same regimen without ursodiol. There were no significant differences in disease or clinical status between the groups pretransplant. However, mean baseline AST levels were significantly higher in the ursodiol group, 28.0 U/l vs 18.1 U/l in the control group (p = 0.001). The median maximum bilirubin observed post-transplant was 2.35 mg/dl (range 0.9-45) in the ursodiol group, and 5.05 mg/dl (range 0.7-29.4) in controls. The incidence of VOD was 2/22 (9.1%) in the ursodiol group and 18/28 (64.3%) in controls (p = 0.0001). Death due to VOD occurred in 1/22 patients (4.5%) in the ursodiol group and in 6/28 (21.4%) controls (p = 0.12). Our data suggest that ursodiol may decrease the incidence of VOD in allogeneic BMT patients.
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PMID:Pilot trial of prophylactic ursodiol to decrease the incidence of veno-occlusive disease of the liver in allogeneic bone marrow transplant patients. 142 93

Recent reports using historical controls or registry cohorts suggest, respectively, either an increase in the mortality or a decrease in the incidence of hepatic veno-occlusive disease (VOD) with the administration of intravenous immunoglobulin (i.v.Ig) after bone marrow transplantation. These divergent results prompted us to conduct a retrospective analysis of two randomized clinical trials conducted at our center to determine the effect of i.v.Ig infusions on the development and severity of VOD. Patients were randomized to receive (n=318) or not to receive (n=315) i.v.Ig prophylaxis after human leukocyte antigen-identical sibling (n=414), mismatched or unrelated (n=178), or autologous or syngeneic (n=41) marrow transplantation. To determine the relationship of i.v.Ig to the development and severity of VOD, a single observer reviewed data displays created for each patient for grading VOD without knowledge of patient i.v.Ig use. In this analysis, VOD was defined as hyperbilirubinemia > or =2.0 mg/dL before day 20 and abrupt weight gain > or =2% before day 14 posttransplant in the absence of other causes of liver disease. Hepatic VOD developed in 235 (37%) of the 633 randomized patients. No evidence for VOD was found in 230 (36%) patients. The remaining 168 (27%) patients were classified as having liver disease of uncertain etiology. Hepatic VOD was judged to be severe in 63 (10%) and mild or moderate in 172 (27%) patients. The number of patients developing any VOD or severe VOD was similar between those randomized to i.v.Ig prophylaxis and untreated controls (115 vs. 120 and 32 vs. 31, respectively). Logistic regression models identified several covariates as significant (p < 0.01) factors associated with the development of severe VOD. Increased risk occurred with elevated pretransplant serum aspartate aminotransferase (odds ratio [OR] = 2.64) and earlier year of transplant (OR = 3.73); decreased risk occurred with autologous or twin donors (OR = 0.09) and acute myeloid leukemia (OR = 0.39). The development of any VOD was associated with an elevated pretransplant alkaline phosphatase (OR = 4.1), pretransplant use of vancomycin (OR = 1.6) or amphotericin (OR = 3.0), posttransplant use of cyclosporine (OR = 2.5), older patient age (OR = 1.03), and obesity (OR = 0.78). We concluded from the controlled trials of 633 patients that the administration of i.v.Ig did not influence the development or severity of VOD after bone marrow transplantation.
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PMID:Intravenous immunoglobulin and the risk of hepatic veno-occlusive disease after bone marrow transplantation. 970 88

To determine the incidence and outcome of hepatic veno-occlusive disease (VOD) after blood or marrow transplantation (BMT), we prospectively evaluated all consecutive patients receiving a BMT during a 6-month period in participating EBMT centers. All of them were evaluated for occurrence of VOD according to previously defined clinical criteria. The clinical course, outcome, value of prophylactic and therapeutic interventions, and the influence of previously described risk factors were analyzed. During the study period, 1,652 BMT were performed in 73 centers. VOD was diagnosed in 87 patients (5.3%; 95% confidence interval [CI], 4.2% to 6.4%). Fifty-six of 631 allogeneic BMT (8.9%) and 31 of 1,010 autologous BMT (3.1%) developed this complication (P <.0001). VOD was classified as mild in 7 (8%), moderate in 56 (64.4%), and severe in 24 (27.6%) cases. Sixteen patients died of VOD (corresponding to 1% of the whole series, 18.4% of VOD patients, and 66.7% of severe VOD). The use of unfractionated heparin did not significantly decrease the incidence of VOD. Independent variables associated with an increased risk of VOD were allogeneic BMT (relative risk [RR], 2.8; P <.001), pre-BMT elevation of serum aspartate aminotransferase (RR, 2.4; P =.001), high-dose cytoreductive therapy (RR, 2.3; P =.003), Karnofsky performance score less than 90% (RR, 2.7; P =.006), and prior abdominal radiation (RR, 2.9; P =.03). In conclusion, this prospective study shows that (1) the incidence of VOD is lower than that reported in smaller studies from single centers, (2) about one fourth of cases of VOD progress to severe disease, (3) main risk factors have a major impact on incidence of VOD, and (4) the use of prophylactic unfractionated heparin does not seem to reduce the incidence of VOD.
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PMID:Incidence and outcome of hepatic veno-occlusive disease after blood or marrow transplantation: a prospective cohort study of the European Group for Blood and Marrow Transplantation. European Group for Blood and Marrow Transplantation Chronic Leukemia Working Party. 980 53

Three patients developed veno-occlusive disease of the liver (VOD) after allogeneic stem cell transplantation. On the day after diagnosis, N-acetylcysteine (NAC) was given, initially in loading doses and thereafter 50-150 mg/kg/day for 12 to 31 days. The maximum bilirubin levels were 137, 58 and 138 mmol/l in the three patients, respectively. After the introduction of NAC, bilirubin, aspartate aminotransferase, sIL-2 receptor and IL-8 decreased. All three patients achieved normal bilirubin levels and prothrombin times. To conclude, NAC may be useful for treatment of VOD.
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PMID:N-acetylcysteine for hepatic veno-occlusive disease after allogeneic stem cell transplantation. 1080 69

This retrospective cohort study of 462 consecutive adult allogeneic and autologous blood or marrow transplantation (BMT) patients compared the incidence of hepatic veno-occlusive disease (VOD) after BMT with three prophylactic regimens. Patients receiving heparin (Hep), heparin + prostaglandin E1 (Hep + PGE1) or low molecular weight heparin (LMWH) as a prophylactic VOD regimen were compared to a historical cohort receiving no VOD prophylaxis. Of 462 BMT patients, VOD was diagnosed in 22% (31 of 142) of the no prophylaxis group, 11% (11 of 104) of the Hep, 12% (13 of 110) in the Hep + PGE1 and 4% (four of 106) of the LMWH group (P = 0.0002). VOD was the primary cause of death in 20% (12 of 59). By multivariate logistic regression, independent risk factors for developing VOD were: no VOD prophylactic regimen, unrelated allogeneic BMT, Karnofsky performance score (KPS) < 80 and aspartate aminotransferase (AST) > or =50 U/l. There was no increase in the rate of death due to hemorrhagic events or VOD in any prophylaxis group compared to the control group. Prospective randomized trials of Hep vs LMWH vs placebo are warranted to assess the efficacy of heparin compounds in the prevention of VOD.
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PMID:Retrospective multivariate analysis of hepatic veno-occlusive disease after blood or marrow transplantation: possible beneficial use of low molecular weight heparin. 1131 93

Actinomycin-D (Act-D) is a rare cause of veno-occlusive disease (VOD). Between 1993 and 1998, we managed 6 patients, all male, median age 19 months (range 6-48 months) who received Act-D for Wilms' tumour (n=4), clear cell sarcoma (n=1) or rhabdomyosarcoma (n=1). VOD presented with a median platelet count of 12 x 10(9)/l, INR 3.8, fibrinogen 16 mg/l, fibrinogen degradation products (FDPs) > or =80 microg/l, aspartate aminotransferase (AST) 6922 IU/l, bilirubin 47 micromol/l. In 3 cases, transient liver dysfunction and thrombocytopenia without neutropenia had been observed after a previous course of Act-D. All six children developed encephalopathy, hepatomegaly, ascites, reversed portal flow and renal impairment. All received mechanical ventilation and two required haemofiltration. The treatment was supportive. Severe Adult Respiratory Distress Syndrome developed in 3 patients, all of whom died. 3 patients recovered. The outcome of VOD with multi-organ failure is poor. Intravascular coagulopathy precedes and characterises severe VOD during Act-D treatment.
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PMID:Veno-occlusive disease with multi-organ involvement following actinomycin-D. 1137 45

We retrospectively analyzed the incidence and risk factors for veno-occlusive disease (VOD) in 83 consecutive children with solid tumors, who underwent autologous blood or bone marrow (BM) transplantation at UCSF between 1992 and 2000. Forty-one patients were diagnosed with neuroblastoma and 42 had another solid tumor (Ewing's sarcoma, soft tissue sarcomas, germ cell tumors, etc). Patients with neuroblastoma were more likely than patients with other solid tumors (ST) to be < or =7 years of age, to have a decreased serum albumin level, and to have received abdominal radiation and surgery prior to transplant. Patients with neuroblastoma received a different conditioning regimen and a purged stem cell product. Twenty patients (24%) developed VOD. VOD was self-limited in 15 (75%) patients and severe in five (25%) patients. Univariate analysis identified the following risk factors for VOD: diagnosis of neuroblastoma (odds ratio 6.1, P < 0.01), abdominal radiation (odds ratio 4.1, P < 0.01), abdominal surgery (odds ratio 4.1, P < 0.01), and age < or =7 years of age (odds ratio 3.3, P = 0.02). Disease status at transplant, intensity of previous chemotherapy, conditioning regimen, progenitor cell source, ALT, AST, albumin level, renal function prior to transplant, or use of amphotericin, growth-factor or heparin during transplant, did not affect the incidence of VOD. On multivariate analysis, only the diagnosis of neuroblastoma remained significant (odds ratio 7.8, P = 0.03). Larger studies of patients with neuroblastoma are necessary in order to confirm our findings and better define the risk factors for VOD development in neuroblastoma patients.
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PMID:Veno-occlusive disease of the liver in children with solid tumors undergoing autologous hematopoietic progenitor cell transplantation: a high incidence in patients with neuroblastoma. 1191 31

Busulfan (Bu) is an important component of some myeloablative regimens prior to stem cell transplantation (SCT). Over the last few years it has been shown that other drugs administered concomitantly can influence Bu pharmacokinetics. In the present study, we compared Bu concentrations (trough levels) in three groups of patients. Group A (n=5) received metronidazole as graft-versus-host disease prophylaxis during Bu treatment. Group B (n=9) received Bu only for 2 days followed by 2 days of Bu and metronidazole. Group C (n=10) was a control group that received Bu without metronidazole. The mean Bu levels for Group A receiving metronidazole during conditioning was significantly (P<0.001) higher (948+/-280 ng/ml), compared to those observed in the control group (507+/-75 ng/ml). In Group B, the administration of metronidazole resulted in a significant (P<0.001) increase in Bu levels (807+/-90 ng/ml) during the last 2 days, compared to 452+/-68 ng/ml during the first 2 days. In Group A, one patient died with multiorgan failure, three experienced veno-occlusive disease (VOD) and one developed hemorrhagic cystitis. Elevated liver transaminases (AST, ALT) and bilirubin were detected in all Group A patients. In Group B, six patients had elevated liver function tests but no VOD was observed. We conclude that metronidazole should not be administered simultaneously with Bu to avoid the high plasma levels of Bu, which may lead to severe toxicity and/or treatment related mortality.
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PMID:The effect of metronidazole on busulfan pharmacokinetics in patients undergoing hematopoietic stem cell transplantation. 1266 36

Patients who will receive chemotherapy require careful assessment of liver function prior to treatment to determine which drugs are not appropriate, and which drugs need dose modification. However, if the hepatic parenchymal abnormalities are caused by an underlying neoplasm and the neoplasm is sensitive to the drugs, it may not be necessary to reduce the dose. Clearly, this is an area where clinical judgment must be used to assess the risk/benefit ratio. Treatment of chronic hepatitis B virus (HBV) involves either the nucleoside analogue lamivudine or interferon alpha. The advantage of lamivudine includes limited adverse effects and the fact that histological improvement has been documented in the majority of patients. Primary prophylaxis with lamivudine may be a well tolerated and effective method to reduce the frequency of chemotherapy-induced HBV reactivation in chronic HbsAg carriers. HbsAg screening is necessary before beginning chemotherapy for non Hodgkin's lymphoma patients. However, the main problem with long-term lamivudine therapy is the emergence of genotypic resistance because of base pair substitution at specific sites within the YMDD locus of the DNA polymerase gene. Significant hepatic dysfunction is uncommon among hepatitis C virus (HCV) infected patients treated with chemotherapy for hematological malignancies. However, infection with elevated AST levels is a significant risk factor for veno-occlusive disease after hematopoietic stem cell transplantation. Clinical judgment and a high index of suspicion remain critical tools in preventing and treating hepatic manifestations of cancer chemotherapy.
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PMID:[Hepatotoxicity of chemotherapy]. 1285 43

Impairment of venous outflow from the liver manifests as zone 3 sinusoidal dilatation and congestion (SDC) in liver biopsy. The spectrum of histologic changes in portal tracts has not been described. We studied liver biopsies from 34 patients with a confirmed diagnosis of venous outflow impairment (VOI). Liver transplant recipients and biopsies with cirrhosis and hepatic neoplasms were excluded. Clinical records were reviewed for laboratory tests and radiographic findings. In all, 19 patients had right heart disease, 13 had classic Budd-Chiari syndrome and two had veno-occlusive disease. Liver chemistry tests showed elevated liver transaminases (n=21; 61.8%), elevated alkaline phosphatase (n=31; 91.2%) and GGT (all 13 cases tested). The elevation in ALT and AST was mild (below 200 U/l in all cases), while alkaline phosphatase (ALP) was elevated above 500 U/l in nine (26.5%) patients and above 1000 U/l in three cases. On biopsy, all cases showed SDC. The portal tracts showed (a) portal expansion with bile ductular proliferation (n=16; 47.1%) accompanied by lymphoplasmacytic infiltrate (n=10), lymphocytic cholangitis (n=3) and portal or periportal fibrosis (n=11), (b) Portal and/or periportal fibrosis without ductular proliferation (n=3; 8.8%) or (c) Normal portal tracts (n=15; 44.1%). The combination of elevated ALP and bile ductular changes on biopsy suggested chronic bile duct disease. Ultrasound/CT scan evaluation of bile ducts in 26 patients showed no biliary tree abnormality. Antimitochondrial antibody testing in eight cases also yielded negative results. In conclusion, bile ductular proliferation, portal inflammation and portal-based fibrosis are commonly seen in liver biopsies of patients with VOI even in the absence of bile duct disease. These changes are often accompanied by elevated ALP and GGT and can lead to the suspicion of chronic biliary disease. In the absence of demonstrable abnormalities in the biliary tree, these changes can be attributed to venous outflow impairment.
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PMID:Histologic changes mimicking biliary disease in liver biopsies with venous outflow impairment. 1509 6


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