Blood Trough Levels Research Articles

Renal function and safety in stable kidney transplant recipients converted from immediate-release to prolonged-release tacrolimus

This multicenter, open, phase IIIb study assessed short-term efficacy, safety and dose adjustments in adult stable renal transplant recipients converted from tacrolimus twice-daily (BID) to once-daily (QD). Patients receiving unchanged tacrolimus BID for ≥ 12 weeks were enrolled, and after 6-weeks, converted from tacrolimus BID to QD (morning dose) on a 1 : 1 (mg : mg) total daily dose basis, for a further 12 weeks. Primary endpoint: change in steady-state creatinine clearance between treatment phases. Secondary endpoints: biopsy-proven acute rejection (BPAR), patient and graft survival, safety. 128 patients enrolled (mean age 48.9 years; time post-transplant 48.9 months); 91 evaluated for the primary endpoint. Mean total daily dose was 0.06 mg/kg (BID) and 0.07 mg/kg (QD); 79.1% required one/no dose changes post-conversion to maintain recommended blood-trough levels; average dose increase was small (0.6-0.7 mg/day) with more dose increases in patients on the lowest tacrolimus BID doses. Renal function remained stable and non-inferiority of tacrolimus QD against tacrolimus BID was demonstrated. There were no BPAR episodes; patient and graft survival were 100%. Adverse events were few; none led to dose modifications/discontinuation. Tacrolimus BID to tacrolimus QD conversion is straightforward and does not compromise renal function in stable kidney transplant patients in the short term.

Effect of a New Functional CYP3A4 Polymorphism on Calcineurin Inhibitors‘ Dose Requirements and Trough Blood Levels in Stable Renal Transplant Patients

CYP3A4 is involved in the oxidative metabolism of many drugs and xenobiotics including the immunosuppressants tacrolimus (Tac) and cyclosporine (CsA). The objective of the study was to assess the potential influence of a new functional SNP in CYP3A4 on the pharmacokinetic parameters assessed by dose requirements and trough blood levels of both calcineurin inhibitors (CNI) in stable renal transplant patients. A total of 99 stable renal transplant patients receiving either Tac (n = 49) or CsA (n = 50) were genotyped for the CYP3A4 intron 6 C>T (rs35599367) and CYP3A5*3 SNPs. Trough blood levels ([Tac](0) or [CsA](0) in ng/ml), dose-adjusted [Tac](0) or [CsA](0) (ng/ml per mg/kg bodyweight) as well as doses (mg/kg bodyweight) required to achieve target concentrations were compared among patients according to allelic status for CYP3A4 and CYP3A5. Dose-adjusted concentrations were 2.0- and 1.6-fold higher in T-variant allele carriers for the CYP3A4 intron 6 C>T SNP compared with homozygous CC for Tac and CsA, respectively. When CYP3A4/CYP3A5 genotypes were combined, the difference was even more striking as the so-defined CYP3A poor metabolizer group presented dose-adjusted concentration 1.6- and 4.1-fold higher for Tac, and 1.5- and 2.2-fold higher for CsA than the intermediate metabolizer and extensive metabolizer groups, respectively. Multiple linear regression analysis revealed that, taken together, both CYP3A4 intron 6 and CYP3A5*3 SNPs explained more than 60 and 20% of the variability observed in dose-adjusted [Tac](0) and [CsA](0), respectively. The CYP3A4 intron 6 C>T polymorphism is associated with altered Tac and CsA metabolism. CYP3A4 intron 6 C>T along with CYP3A5*3 (especially for Tac) pharmacogenetic testing performed just before transplantation may help identifying patients at risk of CNI overexposure and contribute to limit CNI-related nephrotoxicity by refining the starting dose according to their genotype. Original submitted 5 May 2011; Revision submitted 29 June 2011.

Arterial Hypertension in Liver Transplant Recipients

Hypertension is an important cardiovascular risk factor that influences patient survival. This study sought to evaluate hypertension incidence and circadian rhythms of blood pressure (BP) among liver transplant recipients during the first posttransplant month. We also compared hypertension incidence according to clinical and automated blood pressure monitoring methods. BP was determined by clinical blood pressure monitoring (CBPM) methods and by automated blood pressure monitoring (ABPM) using the SpaceLabs device. We also assessed blood biochemistry, particularly kidney function parameters and immunosuppressive drug blood trough levels, among 32 white subjects (10 women and 22 men) of average age 47.58 ± 14.19 years. The leading cause for transplantation was liver insufficiency due to viral hepatitis B and/or C infection (43.75%). The majority (93.75%) of patients was prescribed immunosuppressive treatment with tacrolimus. Although we observed hypertension in 28 patients (87.5%) by ABPM measurements and in 25 (78.12%) using CBPM method, the difference did not reach statistical significance. However, BP control was inadequate in 28 patients (87.5%) by ABPM assessment versus 3 (9.38%) according to CBPM readings ( P = .025). The BP circadian rhythm was altered in 30 patients (93.75%) including 15 with higher nighttime BP readings. There was no correlation between tacrolimus blood levels and BP values or with kidney function as assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. We concluded that prevalence of arterial hypertension among liver transplant recipients within 1 month after transplantation is high. The majority of the patients show disturbed circadian rhythms in the early period after liver transplantation with loss or even reversal of the normal nocturnal decrease in BP. Owing to the fact that ABPM enables more adequate daily assessment of BP values, it is an optimal method to adjust antihypertensive therapy to optimal levels.

Improved Kidney Graft Function After Conversion From Twice Daily Tacrolimus to a Once Daily Prolonged-Release Formulation

Background Tacrolimus once daily (Tac-QD) formulation has been recently introduced to improve patient adherence to immunosuppressive medications. To evaluate long-term effects of conversion from tacrolimus twice daily (Tac-BID) to Tac-QD on kidney graft excretory function, we retrospectively analyzed kidney graft function after the conversion from Tac-BID to Tac-QD over 24 months. Methods We enrolled 72 kidney transplant recipients, including 19 simultaneous pancreas–kidney cases, who were at least 9 months posttransplantation and showed stable graft function for 6 months. We analyzed kidney graft function (glomerular filtration rate [eGFR] by the Modification of Diet in Renal of Disease equation), tacrolimus daily dose and tacrolimus blood trough level changes over 24 months after conversion. Results All patients completed the 12 months and 56 patients, 24 months observation. At 3 months, the eGFR increased significantly after conversion from 57.1 to 60.0 mL/min/1.73 m 2 ( P = .004) and at 24 months to 66.0 mL/min/1.73 m 2 ( P < .001). Tacrolimus daily dose diminished over time by almost 10%, a difference that reached statistical significance at 18 months. Tacrolimus blood trough levels did not change significantly until 24 months. There was no correlation between eGFR changes during the first 12 months after conversion and changes in tacrolimus blood trough levels ( r = −0.118; P = .33). Conclusion Conversion from Tac-BID to Tac-QD formulation was followed by a clinically significant improvement in kidney graft function upon long-term observation. The improvement seemed to not be related to changes in tacrolimus blood trough levels.

How the latest evidence from clinical research informs patient care

How the latest evidence from clinical research informs patient care

Influence of CYP3A5 and ABCB1 gene polymorphisms and other factors on tacrolimus dosing in Caucasian liver and kidney transplant patients

Tacrolimus is a substrate of cytochrome P4503A (CYP3A) enzymes as well as of the drug transporter ABCB1. We have investigated the possible influence of CYP3A5 and ABCB1 single nucleotide polymorphisms (SNPs) and other factors (e.g. albumin, hematocrit and steroids) on tacrolimus blood levels achieved in a population of Caucasian liver (n=51) and kidney (n=50) transplant recipients. At 1, 3 and 6 months after transplantation, tacrolimus doses (mg/kg/day) and trough blood levels (C0) were recorded and the weight-adjusted tacrolimus dosage (mg/kg/day) was calculated. Polymerase chain reaction followed by restriction fragment length polymorphism analysis was used for genotyping CYP3A5*1 and *3 [6986A>G] as well as ABCB1 at exons 21 [2677G>T/A] and 26 [3435C>T] in both liver transplant donors and recipients and in kidney transplant recipients. Of the 152 subjects studied, 84.9% showed a CYP3A5*3/*3 genotype. The total frequency of the allelic variant *3 was 93%. For the G2677T/A and C3435T polymorphisms the total frequencies of the allelic variants T/A and T were 44.7 and 46.7%, respectively. At 1, 3 and 6 months after transplantation the dose-adjusted C0 levels were significantly lower in patients with one copy of the *1 allele compared to those homozygous for the *3 allele. In the case of liver transplant patients the tacrolimus dose requirements were dominantly influenced by the polymorphisms of the CYP3A5 gene in the donors. With regard to the ABCB1 SNPs, in general they did not show any appreciable influence on tacrolimus dosing requirements; however, kidney transplant recipients carrying the 2677T/A allele required significantly higher daily tacrolimus doses than subjects homozygous for the wild-type allele. Identification of CYP3A5 single nucleotide polymorphisms prior to transplantation could contribute to evaluate the appropriate initial dosage of tacrolimus in the patients.

A Retrospective 12-Month Study of Conversion to Everolimus in Lung Transplant Recipients

Background Everolimus has potent antifibrotic effects that may potentially affect the clinical course of bronchiolitis obliterans syndrome (BOS) or provide nephroprotective immunosuppressive regimens for lung transplantation. Methods We retrospectively assessed the 12-month outcomes of the conversion to everolimus among lung recipients in six Spanish centers. Results From March 2005 to December 2007, 65 lung recipients who were at a mean posttransplantation time of 10.2 ± 7.9 months were converted to everolimus, mainly because of BOS (64.6%) or renal insufficiency (RI; 12.3%). The initial dose of everolimus was 1.9 ± 0.6 mg/d and the mean blood trough levels were stable over time (6.4 ± 2.8 ng/mL at 12 months). Conversion to everolimus allowed us to eliminate the calcineurin inhibitor (CNI) in 21% of patients. Among the overall population, the forced expiratory volume at 1 second (FEV 1) and renal function remained stable. Mean FEV 1 did not change among the 35 (81%) patients surviving BOS at 12 months: preconversion FEV 1: 1.449.5 ± 641.9 mL vs 12-month FEV 1: 1420.0 ± 734.6 mL ( P = .866). There was a significant improvement in renal function among the RI patients with mean glomerular filtration rates of 42.2 ± 15.2 mL/min/1.73 m 2 ( P = .043) at 6 and 44.4 ± 18.8 mL/min/1.73 m 2 at 12 months, ( P = .063) and a decrease in the use of CNIs from 1% of RI patients preconversion to 57% at 6 and 75% at 12 months. With a mean of 8.1- months follow-up (range: 1–31.3) overall survival was 84.6% at 1 year and 50% at 22.3 months. Progressive BOS was the main cause of death. Reasons for everolimus discontinuation were patient death ( n = 10), lack of efficacy ( n = 4), gastrointestinal adverse events ( n = 2), and edema ( n = 2). Conclusions BOS and RI were the main indications for conversion to everolimus among lung recipients. Conversion to everolimus improved renal function among patients converted because of RI. The present results were inconclusive regarding effects of everolimus on BOS.

Pharmacokinetic Differences Corroborate Observed Low Tacrolimus Dosage in Native American Renal Transplant Patients

We have observed in clinical practice that Native Americans require lower dosages of tacrolimus to attain similar target blood trough levels compared to whites after renal transplant. Because there are no pharmacokinetic studies of tacrolimus in this ethnic group, we investigated whether this clinical observation could be corroborated by pharmacokinetic differences between Native Americans and other ethnic and racial groups. We recruited 24 adult Native American kidney transplant recipients on stable oral doses of tacrolimus for at least 1 month posttransplant. We conducted a 12-h steady-state pharmacokinetic profile for all of the patients and estimated pharmacokinetic parameters using NONMEM. The concentration-time data were fit to a linear two compartment model with first-order absorption and lag time using an empirical Bayesian approach. The mean estimate of oral clearance (CL/F) was 11.1 l/h. Compared with previously reported data in other ethnic and racial groups, the Native American cohort has approximately one third the clearance of other groups. Our pharmacokinetic study reveals the clinically observed low dose of tacrolimus in Native American renal transplant patients is associated with a decreased oral tacrolimus clearance. There is scant information available on the genetic or environmental characteristics unique to this ethnic group that affect pharmacokinetics compared to other, better-studied groups, and elucidation of these factors will provide information to further facilitate individualized drug treatment for tacrolimus and a wide range of other drugs with similar clearance processes.

Sirolimus and Proteinuria in Renal Transplant Patients: Evidence for a Dose-Dependent Effect on Slit Diaphragm-Associated Proteins

The mechanisms underlying the development of proteinuria in renal-transplant recipients converted from calcineurin inhibitors to sirolimus are still unknown. This is a single-center cohort study. One hundred ten kidney transplant recipients converted from calcineurin inhibitors to sirolimus in the period from September 2000 to December 2005 were included in the study. All patients underwent a graft biopsy before conversion (T0) and a second protocol biopsy 2 years thereafter (T2), according to our standard clinical protocol. On the basis of the changes observed in proteinuria between T0 and T2 (median 70%), the patients were divided into two groups: group I (<70%) and group II (>70%). The authors blinded the sirolimus blood trough levels. We investigated in vivo the effects of sirolimus on nephrin, podocin, CD2ap, and actin protein expression. Slit diaphragm (SD)-associated protein expressions were evaluated in T0 and T2 biopsies. The same analysis was performed in cultured human podocytes treated with different doses of sirolimus (5, 10, 20, and 50 ng/mL). The SD protein expression in group II T2 biopsies was significantly reduced compared with the T0 biopsies and with T2 group I biopsies. In addition, sirolimus blood trough levels directly and significantly correlated with the SD protein expression at T2 graft biopsies. Group II patients presented significantly higher sirolimus blood levels than group I. In vitro study confirmed that sirolimus effect on podocytes was dose dependent. Our data suggest that sirolimus-induced proteinuria may be a dose-dependent effect of the drug on key podocyte structures.

Once-a-Day Administration of Everolimus Is Safe in De Novo Renal Transplant Recipients: 1-Year Results of a Pilot Study

Introduction The half-life of everolimus is approximately 28 hours, but everolimus is generally administered twice a day. The aim of this prospective, single-center, exploratory study was to compare the efficacy and safety of a once a day everolimus (OD) with the standard twice a day administration regimen (BID) as immunosuppressive therapy in renal transplantation. Methods Forty-one de novo renal transplant recipients prospectively assigned to OD ( n = 21) or BID ( n = 20) treatment were followed for 1 year. In the OD group, everolimus was orally administered targeting a trough blood level of 2 to 5 ng/mL. In the BID group, everolimus was given twice a day targeting a trough blood level of 3 to 12 ng/mL. All patients also received induction with basiliximab and low-dose calcineurin inhibitor immunosuppression. Results At 1 year follow-up patient and graft survivals were 100%. The intention-to-treat analysis showed similar renal function between the two regimens: serum creatinine values for OD 1.54 ± 0.6 versus BID 1.48 ± 0.53 mg/dL ( P = NS). Also the occurrence of acute rejection episodes was not significantly different: 4.8% in the OD versus 15% in the BID group, ( P = NS). The median trough blood levels were significantly lower among the OD group: OD 4.5 versus BID 7.2 ng/mL ( P < .001). Discussion This study demonstrated that once a day administration of everolimus achieved excellent patient and graft survival and good renal function without an increased incidence of acute rejection episodes.

Abstract 1309: Human imatinib (IM) and desmethyl-IM blood vs. tissue levels in healthy and tumor tissue of patients treated for advanced gastrointestinal stromal tumors (GIST)

Abstract Background: Blood trough levels of 1100 ng/ml are thought to be required for effective treatment of CML with IM. In a solid tumor like GIST, there might be different access of tumors cells to the drug even depending on the harbouring organ. There are no data available comparing tissue and blood levels of IM in humans. Materials: 24 patients scheduled for tumor resection were treated with IM 400mg/d or bid for metastatic GIST and medication continued including the preop. day. Blood samples were drawn intraop. at the time of resection. Samples of tumor tissues (n=52) and healthy organ tissues the tumor grew in were taken from 28 locations: liver (n=12), omentum (n=7), stomach (n=5), small bowel (n=2), soft tissue (n=1) and lung (n=1). Methods: To quantify IM in serum and tissue specimens a LC-MS/MS assay linear for concentrations 10 – 5000 ng/ml was used. IM and internal standard D8-IM were extracted from plasma specimens and corresponding tissue of GIST-pats. with ion exchange cartridges (OASIS MCX). Extracts were injected into the HPLC system equipped with XBridge phenyl column (Waters Corp.) and the non-isocratic elution with a mobile phase consisting of methanol/ammonium formate (4mM, pH4) performed within 15 minutes at a flow rate of 0,3ml/min. Ion transitions [M + H]+ of IM (m/z = 494 –&amp;gt; 394), DM-IM (m/z 480–&amp;gt; 394) and of D8-IM (m/z 502–&amp;gt; 394) were monitored by MRM mode. The mass spectrometer HCT Ultra (Bruker Daltonics) was equipped with an electro spray ionization probe, operating in positive mode. Peak areas and respective concentrations of DM-IM were calculated with QuantAnalysis (Bruker Daltonics). A six-point calibration for IM was performed once a day before analytical runs and quality control specimens with 3 different concentration-ranges (20, 100 and 1000 ng/ml). The interday precisions for the low level quality control (20 ng/ml) was below 20% and below 10% for the medium (100 ng/ml) and high (1000ng/ml) – levels respectively. Tissue IM/DM-IM data are given as ng/mg tissue, and mean+/SD. Correlations were calculated using Spearman and Pearson tests. Results: IM blood levels were 997+/-265 ng/ml (range 225-2760), and DM-IM were 215 +/- 124 ng/ml (range, 29-399), correlated with r=0.74. There was a significant difference between organs: liver IM 16,8 +/6.2 (DM-IM 13.2 +/4.5), stomach IM 5.25 +/- 1.2 (DM-IM 4.12 +/- 1.1), omentum IM 1.25 (DM-IM 2.1), p&amp;lt;0.01 and only a weak correlation to blood IM levels (r=.45). Tumor concentrations of IM were 40+/-12 (DM-IM 18.6 +/- 14) There was only a moderate correlation (r=.486, p=.021,) between blood levels of IM and tumor tissue (DM-IM r=0.34, p 0.06). Conclusions: In humans, tissue concentrations of imatinib cannot be predicted from blood levels, neither in healthy organs, nor in GIST tumor tissue. Different tissue IM levels could explain tumor progression during therapy despite of the missing of secondary mutations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1309. doi:10.1158/1538-7445.AM2011-1309

Advagraf De Novo in Liver Transplantation: A Single-Center Experience

Advagraf, a prolonged release formulation of tacrolimus, is administered once daily in the morning. The aim of this study was to show the results obtained in our center, analyzing the safety, efficacy, blood trough levels, and drug doses. Methods We analyzed 50 consecutive recipients of a first liver transplantation with 6 months follow-up. Efficacy and safety variables were collected as the incidence of acute rejection episodes, patient and graft survivals, kidney function as well as incidences of diabetes mellitus and arterial hypertension de novo. Results The incidence of biopsy proven acute rejection episodes was 10% ( n = 5), none 7 of which were steroid resistant and all resolved favorably. The rate of diabetes mellitus de novo was 22% ( n = 11), 7 of whom required insulin. Hypertension developed in 9 patients (18%), all of whom were treated with a single drug. The mean serum creatinine level was 1.08 ± 0.25 mg/dL, with 3 patients (6%) displaying a value ≥ 1.5 mg/dL. Patient and graft survivals were 100%. Conclusion Advagraf is an effective immunosuppressant in liver transplantation with a low incidence of biopsy-confirmed acute rejection episodes. The good results for patient and graft survival with few side effects make it a useful drug for de novo liver transplantation.

A Prospective, Multicenter Study of Once-Daily Extended-Release Tacrolimus in De Novo Liver Transplant Recipients

To minimize noncompliance in organ transplantation, a new formulation was developed of once-daily extended-release (EXTD) tacrolimus. To analyze the efficacy and safety of this new drug formulation in de novo liver transplant recipients, a prospective, multicenter study was performed in six centers in Spain. The primary objective of the study was to evaluate the incidence of biopsy-proven acute rejection episodes (BPAR) according to the BANFF criteria during the first 3 months of immunosuppression with the EXTD formulation of tacrolimus. Fifty-two patients received a mean initial dose of 10.0 ± 3.8 mg that was gradually reduced to 7.1 ± 4.0 mg, achieving stable mean blood levels of 8.6 ± 3.7 ng/mL at 3 months. BPAR was reported in seven (13%) patients, but patient and graft survivals were 100%. After transplantation liver function improved and was stably maintained throughout the study. At 3 months, mean bilirubin levels were 2.1 ± 5.5 mg/dL and mean alanine aminotransferase and aspartate aminotransferase were 61.6 ± 75.2 U/L and 55.2 ± 76.9 U/L, respectively. Mean serum creatinine of 0.8 ± 0.3 mg/dL pretransplant increased to 1.1 ± 0.4 mg/dL after 3 months ( P < .0001). There was no significant increase in the rate of hypertension from pretransplant levels: 30% at baseline versus 31% at 3 months. Mean glucose levels did not change significantly throughout the study. There were no cases of hepatitis C virus relapse. EXTD tacrolimus demonstrated excellent stability in blood trough levels with a good efficacy and safety profile in de novo liver transplant recipients that was similar to the well-described properties of standard-release twice-daily formulation of tacrolimus.

Successful liver transplantation from a living donor with asymptomatic pulmonary cryptococcosis

Successful liver transplantation from a living donor with asymptomatic pulmonary cryptococcosis

ABCB1 Single-Nucleotide Polymorphisms Determine Tacrolimus Response in Patients With Ulcerative Colitis

Tacrolimus (Tac) is effective in the treatment of steroid-refractory ulcerative colitis (UC); however, nonresponse and unpredictable side effects are major limitations. Because Tac response in patients who have undergone solid-organ transplantation has been associated with the presence of variants in CYP3A and ABCB1, we elucidated the contributions of CYP3A4*1B and CYP3A5*3 and of ABCB1 1236C>T, 2677G>T,A, and 3435C>T polymorphisms to Tac response in 89 patients with UC. Short-term remission and response were achieved in 61 and 14% of the patients, respectively, and were associated with colectomy-free survival. In a linear logistic regression model, patients with homozygous variants for one of the three ABCB1 alleles showed significantly higher short-term remission rates as compared with those of other genotypes. The effects held true after multivariate analysis including multiple comparisons and were more pronounced after correction for dose-adjusted Tac blood trough levels. We suggest that ABCB1, but not CYP3A5, may predict short-term remission of Tac in steroid-refractory UC.

Clinical outcome in cardiac transplant recipients with chronic kidney disease under high dose and low dose everolimus therapy

Objective: The reference range for everolimus (EVL) blood trough levels is 3–8µg/l. It is currently not known whether patients would benefit from a low or high EVL target value.

Is Chloroquine Making a Comeback?

Is Chloroquine Making a Comeback?

Customized Mycophenolate Dosing Based on Measuring Inosine-Monophosphate Dehydrogenase Activity Significantly Improves Patients' Outcomes After Renal Transplantation

Significant relationships have been reported between the uptake of mycophenolic acid (MPA) and the risk of acute rejection. In a prospective study after renal transplantation, we assessed the value of measuring inosine-monophosphate dehydrogenase (IMPDH) activity as a predictive indicator of an acute rejection episode in the initial postoperative period. Fifty-two patients received 360 mg enteric-coated mycophenolate-sodium two times per day with concomitant tacrolimus/cyclosporine A, providing a total of 122 pharmacodynamic profiles. IMPDH activity was measured by a validated high-performance liquid chromatography method in four plasma samples collected at predose, 30 and 60 min, 2 and 4 hr, and preoperative, during weeks 1 and 2 and 3 months after transplantation. MPA concentrations were measured by mass spectrometry. Inhibition of IMPDH was correlated to the MPA values, MPA area under the curves, and predose levels of the different calcineurin inhibitors. Comparing the two groups (group I: rejection; n=17; mean age 51±15 years vs. group II: no rejection; n=35; mean age 51±14 years), we found a significantly (P<0.001) lower inhibition of IMPDH in group I (26.5%±11% vs. 56.7%±18%) already in the first week after transplantation. There was no correlation of MPA values (6.85±4 vs. 4.1±3 mg/L; first week) nor with the calcineurin inhibitor trough blood levels. Area under the curves for MPA did not differ significantly. Furthermore, IMPDH activity was a reliable predictor of rejection episodes and inflammation. The data suggest that measuring biologic response may be a more valuable indicator than traditional therapeutic drug monitoring of MPA. Patients at risk for rejection could be earlier identified, and the therapeutic potential of MPA will be optimized.

Long-term care following paediatric liver transplantation

Liver transplantation in childhood has evolved quickly and is now a highly successful treatment for end-stage liver disease. One-year survival is greater than 90% in experienced centres, and the vast...

Severe H1N1 Infection in a Pediatric Liver Transplant Recipient Treated With Intravenous Zanamivir: Efficiency and Complications

Severe H1N1 Infection in a Pediatric Liver Transplant Recipient Treated With Intravenous Zanamivir: Efficiency and Complications