Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic allograft nephropathy (CAN), cardiovascular mortality, and posttransplant malignancy are complications of conventional immunosuppression after kidney transplantation. The aim was to study feasibility of sirolimus (SRL) maintenance monotherapy in a pilot experience. All patients with SRL monotherapy of at least 6 months follow-up were included. In 19 patients, age 58 (34-74) years, SRL monotherapy was introduced 98.1 (49-193) months after transplantation by withdrawing concomitant immunosuppressants from protocols already including SRL or introducing SRL and withdrawing other immunosuppressants. Follow-up is 20.0 (6-41) months. One patient died from hepatocellular carcinoma, diagnosed before SRL monotherapy, with functioning graft. No rejections occurred. SRL trough concentration was 10.7 (4.6-16.1) microg/L. Creatinine (1.77 [1.0-2.9] mg/dL vs. 1.68 [0.8-3.3] mg/dL after 6 months, 1.97 [0.8-4.6] mg/dL at last follow-up; P=NS). Proteinuria increased tendentially (333 [67-893] vs. 890 [46-4011] mg/day). No significant changes of hemoglobin, triglycerides, or cholesterol occurred. SRL monotherapy late after kidney transplantation is feasible in selected patients.
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PMID:Sirolimus monotherapy: feasible immunosuppression for long-term follow-up of kidney transplantation--a pilot experience. 1631 5

Model for end-stage liver disease (MELD) score is a good parameter to establish the patient survival before liver transplantation and give priority to the sickest patients. The aim of this study was to evaluate the variability and potential regression of MELD score during the months before liver transplant. From the 350 patients waitlisted for transplantation, we evaluated the 124 patients who had enough blood tests during 12 months before the final event (transplantation, death, removal from list due to improvement or worsening). We considered month 12 as the final event and blood tests from 0, 3, 6, and 12 months were analyzed. MELD score was calculated and compared using ANOVA for repeated measures test. To determine variability of MELD and its components, intraclass correlation coefficient (ICC) was calculated for 0, 3, and 6 months. The degree of constancy was defined by proximity of ICC to 1. Two groups by initial MELD (< or =17 or >17) were considered. Patient data are: mean age, 53 +/- 9 years; sex: 70% men, etiology, 28% hepatitis C, 11% alcohol and hepatitis C, 16% alcohol, 28% hepatocellular carcinoma, 6% hepatitis B, 11% others; Initial Child-score, 8.5 +/- 2.0; Initial MELD score, 15.2 +/- 4.9; mean time on waiting list, 8.1 +/- 5.7 months. MELD score from 6 and 12 months was significantly higher than the initial one. The most constant parameter was creatinine (ICC:0.89); bilirubin (ICC:0.58) and INR (ICC:0.59) were the most variable ones. MELD score ICC was 0.79. In only one patient did MELD score decrease 5 points below the initial one. For initial MELD < or = 17 and >17, variability was lower in the former. In conclusion, MELD became significantly higher 6 months after the basal determination. This score is reliable as it does not tend to decrease in time. In high MELD scores (>17), 3-month survival was lower and variability greater so that more careful follow-up and prioritizing are needed.
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PMID:Variability of MELD score during the year before liver transplantation. 1638 73

We report validation of the first isotope dilution mass spectrometry method for determination of aflatoxin B(1)-N(7)-guanine (AFB(1)-N(7)-Gua), a major human aflatoxin-DNA adduct that is excreted in the urine. Measurement of urinary AFB(1)-N(7)-Gua, a biomarker of the biologically effective dose following dietary aflatoxin B(1) (AFB(1)) exposure, has helped identify AFB(1) as a risk factor in the development of hepatocellular carcinoma, a common cancer worldwide. Triple-quadrupole mass spectrometry, coupled with the use of a stable isotope-labeled internal standard (AFB(1)-N(7)-(15)N(5)-Gua) and better solid phase extraction and immunoaffinity column chromatography, have enabled us to greatly improve accuracy, precision, specificity, and sensitivity over previously published determinations. The limit of quantitation for AFB(1)-N(7)-Gua was 0.8 pg/20 mL urine (0.07 pg/mg creatinine). The method was validated for accuracy and precision over the range of 0.8-25 pg/20 mL urine, with between-day and within-day reproducibility for analysis of six aliquots of a human urine sample containing 6.0 pg/20 mL measured at <6% coefficient of variation. AFB(1)-N(7)-Gua concentrations were measured in 20 human urine samples collected in a region with known aflatoxin exposure. The mean concentration of AFB(1)-N(7)-Gua, measured in 16/20 urine samples with levels above the method's limit of quantitation, was 2.9 pg/20 mL urine (0.28 pg/mg creatinine) with a range of <0.8-7.2 pg/20 mL urine (0.04-65 pg/mg creatinine). With improved accuracy and precision, this sensitive biomarker for recent human exposure to AFB(1) will be especially useful for measuring the efficacy of planned interventions to reduce aflatoxin-related liver cancer in AFB(1)-exposed populations.
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PMID:Quantification of aflatoxin-B1-N7-Guanine in human urine by high-performance liquid chromatography and isotope dilution tandem mass spectrometry. 1697 23

Small uncontrolled series have suggested that sirolimus favorably impacts renal function after orthotopic liver transplantation (OLT). We sought to retrospectively compare renal dysfunction between cohorts exposed to sirolimus-based and calcineurin inhibitor-based immunosuppression. We retrospectively studied 79 patients converted to sirolimus-based immunosuppression and 100 control subjects continued on calcineurin inhibitor-based immunosuppression after OLT at our institution from 2000 to 2005. We collected clinical, demographic, and medication history. Renal dysfunction was defined as two or more wk of creatinine > or =2.0 mg/dL. Cohorts were compared using Kaplan-Meier survival analysis and Cox proportional hazards modeling. Patients began sirolimus a median 83 d post-OLT and were followed on the medication for median 359 d. Patients in both the sirolimus and calcineurin inhibitor cohorts had median creatinine 1.2 mg/dL at study entry. Sirolimus-based immunosuppression was associated with a 1.8 (0.8-4.3, p = 0.17) hazards ratio for renal dysfunction. Adjusting for presence of hepatocellular carcinoma, combined kidney/liver transplantation, and age, the hazards ratio was 2.0 (0.8-4.8, p = 0.13). These point estimates were not substantially altered after subgroup analysis of sirolimus as the lone immunosuppressant, duration of exposure, and time between OLT and sirolimus conversion. In conclusion, our retrospective, controlled study showed that conversion to sirolimus after OLT did not protect against renal dysfunction. The effect of sirolimus on renal function will need to be prospectively evaluated in a prospective, randomized trial.
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PMID:Effects of sirolimus vs. calcineurin inhibitors on renal dysfunction after orthotopic liver transplantation. 1748 88

The enteric-coated mycophenolate sodium (EC-MPS) is a new formulation of mycophenolic acid with a gastro-resistant enteric coating, which releases the drug in the intestine, reducing the incidence of the gastrointestinal (GI) adverse effects. The present work provided a summary of 20 patients with liver transplantation and more than a 1 year of treatment with mycophenolate mofetil (MMF) who, after presentation of GI complications, were converted to EC-MPS. The patients were followed over a 3-month period after beginning EC-MPS treatment. The mean age of the cohort was 53 +/- 10 years and included 75% men. The reasons for transplantation were ethanol cirrhosis (70%), hepatitis C cirrhosis (30%), hepatocarcinoma (5%), and Wilson's disease (5%). At baseline, all patients were being treated with cyclosporine (CsA). CsA doses and levels were reduced during follow-up: baseline dose 179 mg/day versus 143 mg/day at 3 months; levels: 90.4 ng/mL versus 85.8 ng/mL, respectively (P = .017). The administered dose of EC-MPS was 720 mg/day in all cases. The GI complications at baseline were: diarrhea 60% (92% moderate-severe), abdominal discomfort 60% (58% moderate), abdominal pain 45% (44% moderate-severe), gas 40% (38% moderate-severe), nausea 20% (25% moderate), and dyspepsia 20% (mild). After 3 months of EC-MPS treatment, only two patients (10%) displayed moderate diarrhea. The renal evolution was favorable, serum creatinine was reduced, and 24-hour creatinine clearance significantly increased (creatinine: 1.78 +/- 1.6 mg/dL at baseline versus 1.30 +/- 0.3 mg/dL at 3 months, P = .002; creatinine clearance: 72.8 +/- 18 mL/min versus 79.6 +/- 13 mL/min, P = .001). Conversion of MMF to EC-MPS in liver transplant recipients solved the GI tolerability problems and improved renal function during the first 3 months, probably due to the concomitant reduction of anticalcineurinic dose.
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PMID:Clinical evolution in the first 3 months of patients after liver transplantation in maintenance phase converted from mycophenolate mofetil to mycophenolate sodium due to gastrointestinal complications. 1788 75

Experience with sirolimus (SRL)-based immunosuppression following orthotopic liver transplantation (OLT) is rapidly accumulating. In combination with calcineurin inhibitors (CNIs), SRL may reduce the incidence of acute rejection and lower overall required drug levels. This study sought to quantify long-term outcome following OLT in patients with cirrhosis and concomitant hepatocellular carcinoma (HCC) who were treated with an SRL-based regimen as a primary therapy. From January 2000 to June 2007, 97 patients underwent OLT for end-stage liver disease and HCC at the University of Colorado Health Sciences Center. Of those, 45 patients received SRL, in addition to CNIs, as a component of their primary immunosuppression regimen post-OLT. Conversely, 52 patients received the standard immunosuppression regimen including CNIs, mycophenolate mofetil, and corticosteroids. The 2 treatment groups were compared with respect to the following variables: age, gender, tumor stage by explant, grade, size, presence of vascular invasion, focality, Child's class, baseline creatinine, and warm and cold ischemic times. The 2 groups were comparable by all factors save for cold ischemic time, which was significantly longer in the CNI-treated group. Overall survival at 1 and 5 years post-OLT for patients treated with SRL was 95.5% and 78.8%, respectively. Conversely, survival in patients treated with CNIs exclusively at the same time intervals was 83% and 62%. Although there was no difference in the incidence of major complications, the SRL group experienced a modest improvement in renal function. Cumulatively, these data suggest a potential survival benefit with SRL-based therapy in patients undergoing OLT for end-stage liver disease and concomitant malignancy.
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PMID:Sirolimus-based immunosuppression following liver transplantation for hepatocellular carcinoma. 1832 56

Thalassemic diseases including homozygous beta-thalassemia and beta-thalassemia/Hb E (beta-Thal/Hb E) are prevalent in Southeast Asia. Iron overload is a common complication in beta-thalassemia patients which induces intracellular oxidative stress and lipid peroxidation (LPO). LPO end products generate miscoding etheno adducts in DNA which after their repair are excreted in urine. We investigated whether urinary levels of 1,N6-ethenodeoxyadenosine (epsilondA) and 3,N4-ethenodeoxycytidine (epsilondC) can serve as putative cancer risk markers in beta-Thal/Hb E patients. epsilondA and epsilondC levels were assayed in collected urine samples by immunoprecipitation-HPLC-fluorescence and 32P-postlabeling TLC, respectively. Mean epsilondA (fmol/micromol creatinine) levels in urine of beta-Thal/Hb E patients ranged from 4.8 to 120.4 (33.8+/-3.9; n=37) and were 8.7 times higher compared to asymptomatic controls (1.4-13.8; 3.9+/-0.8; n=20). The respective epsilondC levels ranged from 0.15 to 32.5 (5.2+/-1.3; n=37) and were increased some 13 times over controls (0.04-1.2; 0.4+/-0.7; n=20). epsilondC levels were correlated positively with NTBI (r=0.517; P=0.002), whereas epsilondA showed only a trend (r=0.257; P=0.124). We conclude that the strongly increased urinary excretion of etheno adducts indicates elevated LPO-induced DNA damage in internal organs such as the liver. These highly promutagenic lesions may contribute to the increased risk of thalassemia patients to develop hepatocellular carcinoma.
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PMID:Increased urinary 1,N6-ethenodeoxyadenosine and 3,N4-ethenodeoxycytidine excretion in thalassemia patients: markers for lipid peroxidation-induced DNA damage. 1834 16

The objective of this study was to update the clinical issues of acute intermittent porphyria (AIP), as they have not been in focus for years, and to be aware of potentially associated disorders and social consequences. A total of 356 gene carriers of AIP from northern Sweden participated in this retrospective population-based study. Eight mutations were found with a predominance of W198X (89%). Clinical manifestations of AIP (manifest AIP) were identified in 42%, 65% were women. Women were more severely stricken by AIP attacks concerning number and duration, hospital admission and early onset. Men reporting most attacks were > 40 years of age. In addition to traditional symptoms during attacks, fatigue was commonly described. Chronic AIP symptoms and disability pension due to AIP were reported in about 20% of subjects. Precipitating factors were reported with evident sex differences. Half of the gene carriers who were on medications used drugs considered not safe (in 1999), mainly antihypertensive drugs. Smoking was associated with high AIP attack frequency. Elevated levels of ALT, bile acids, creatinine, U-ALA and U-PBG and decreased levels of creatinine clearance were associated with manifest AIP. The same was true for hypertension and myalgia in the legs. Hepatoma was strikingly overrepresented. The high prevalence of manifest AIP in this study could be explained by a mutation-dependent penetrance. Our results emphasize the importance of early diagnosis, counselling and treatment of attacks, screening and treatment of associated disorders.
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PMID:Clinical aspects of acute intermittent porphyria in northern Sweden: a population-based study. 1940 33

Although metabolome research is a rapidly expanding field in the postgenomic era, no single method exists for complete analysis of all the constituents of a metabolome. In this study, we developed a metabolome analysis method using a combination of capillary electrochromatography and electrospray ionization-mass spectrometry. The capillary electrochromatography column was prepared by surface modification of silica compounds (tetraethoxysilane and octyltriethoxysilane) in a fused-silica capillary column. The method was used to separate more than 100 charged and neutral compounds simultaneously. When 1 mM formic acid was used as the eluent, the cationic compounds were eluted rapidly, and then neutral and anionic compounds were eluted (in that order). The developed system was used to analyze the metabolome of a human hepatocellular carcinoma cell line (HepG2). Thirty-three peaks were detected, and eighteen compounds were identified, including marker compounds of hepatocellular cell activity, such as creatinine and homocysteine. Thus, the system was useful not only for metabolome analysis but also for diagnostic measurements of cell function.
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PMID:A capillary electrochromatography-electron spray ionization-mass spectrometry method for simultaneous analysis of charged and neutral constituents of a hepatocarcinoma cell metabolome. 1961 81

Mutations in hemochromatosis gene cause an inappropriately high absorption of iron that induces iron overload and deposition in several tissues, such as liver, pancreas, and heart. Iron overload in the liver has been associated with a high risk of hepatocarcinoma and susceptibility to viral and bacterial infections. The aim of this study was to describe the frequencies of HFE mutations among a kidney transplant population with versus without hepatitis C virus (HCV) infection, and its influence on liver and kidney status parameters. We selected 3 populations: 2 groups of kidney transplant recipients-59 with and 60 without HCV infection-and a third control group of 50 healthy subjects. We collected clinical data concerning liver and kidney status, such as iron, ferritin, albumin, creatinine, gamma GGT, GOT, proteinuria, %prothrombin, and Bilirubin. HFE mutations among patients and controls were determined by polymerase chain reaction-restriction fragment length polymorphism using DNA from the peripheral blood. We observed no significant difference with respect to the frequencies of HFE mutations between controls and patients with versus without HCV infection. Finally comparison of HFE positive versus negative mutation carriers in both groups suggest that any clinical parameter is associated with HFE mutations.
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PMID:Frequency and influence of hemochromatosis gene mutations in kidney transplant recipients with or without hepatitis C virus infection. 1971 39


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