Serum Albumin, Nutritional Risk Assessment, Body Mass Index and the Bioimpedance Analysis in the Assessment of Malnutrition in Patients Up to 15 Years After Liver Transplantation (original) (raw)
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Metabolism and liver transplantation: Review of perioperative issues
Liver Transplantation, 2000
T vidu.il ccll and i t s tiiciiit)ranc structure, transport iiroccssrs, ;ind subccllular componcnts. Functioning ;it tlic hclicst of a vast gcnrtic library, cells ;ind intcractions bcrween cclls and organs control the well-being of organisms. Whcn gcncs (agc, genetic tlisciisc, ctc), toxins, and tr;iuni;i intcrfcrc, thc cffcct on mctdiolic proccsscs can bc profound, long lasting, and lifc thrcatcning. Mcuholisnr in cirrhosis is a protcm topic worthy of niultivolunic texts. A rcvicw of the nictabolic issues in the pcriopcmtivc pcriod is likrwisc a broad topic. Ranging from mct;iholic chiingcs ;ifkting thc organ donor to thosc sccn in thc tr;insplant recipiciit before and afrcr trans~~iatitiitioii, this topic i s worthy of many relatcd prcmitations. I ablc 1 I ' lists somc of thc inborn crrors of mctaholisni that ;irc virtually curcd by coniplctc or scgmcnt;il livcr tr;iiirpl;iiitnrion. 'I'hcse fascinating conditions span boil1 thr prdi;itric ;ind adult pitient popihions. Although thesc conditions can c~i~i s c profound nictabolic chaiigcs, thcy ;ire Iwyontl tlic scope of this rcvicw. C itcriii f i w o r p i almtion in gcncrd arc dcpciidnir on t hc rllmts oft tic ;ictitc p n~c w Icading t o dcath. doiior agc, and prccxisriiig cornorbid diwuc. Such criteria ofien arc hcticr suitd IO judg tlic quality ofthc lir;irt, lung, kidnq, piiitwii+, ;iiiil Iwwcl tlonor thiiii thc Iwtcntinl livcr dotior. hct~tir;ircly jtidfiinfi dic firnctional 1x)rentiiiI of a traiispl.intctl livcr rciii;iiiis iiii rlusivc gwl, cspmi;iIIy in inaqiniI tloiior scrtinp. hliliougli sonic of ihc prohlcnis ;itlKriiig die donor .aid ihc t l d i t y of'thc doiior ogiiii grritly nf?mt the "vciitti;iI rcuipicnt, cvillti,ltioli ofthc tlonor liver is also iioi covcrrtl in i b i s rcvicw. .. Metabolic Problems During the Derioperative Period Liver transplantation is performed primarily in patients who have been ill for a lengthy period. Multisystemic ctTects of cirrhosis include a host of interrelated metabolic proccsscs (Table 2). This review assunies that sonic o r all of these perturbations are present and focuses on issues of concern. Acid-Base Considerations Although both rcspiratory and metabolic acidosis occur during the course of cirrhosis$-" the handling of metabolic acids is often abnormal by the time patients present for transplantation. Because of its metabolism of orginic acid anions, primarily lactate and certain Jmino acids, the livcr has an important influence on normal acid-base homeostasis. The liver is also the primary source of urea production, a process that consumes bicarbonate (Fig. I), but the importance of this to acid-base balance is debated. Some have suggested that hcpatic urea synthesis has a role in acid-basc baliinrc similar to that of the kidneys and lungs,' leading to thc assertion that decreased urea synthesis is largely rcsponsible for the metabolic alkaosis often scen in cnd-stagc liver diseasc (ESLD)."" Others have argued that, when alkalosis is present, respiratory changes arc thc prcdorninant cause, or that many cirrhotics have virtually undcrcctable acid-base abnormalities. Using a rcchniqite that involvcd infusing "N, urea in cirrhotic piticnts, strong cvidrnce was recently provided that the decrcased urea production is not only not associated with decreased plasma urea nitrogen, but also that it docs not appear to affect acid-base balance.'' Early in thc course of the liver transplantation surgical proccdure, significant alkalosis is generally not a prohlcm. Howevcr. in the late operative and early post
Journal of Clinical Pharmacy and Therapeutics, 2006
Background and objectives: Alternative measures to trough concentrations [non-trough concentrations and limited area under the concentrationtime curve (AUC)] have been shown to better predict tacrolimus AUC. The aim of this study was to determine if these are also better predictors of adverse outcomes in long term liver transplant recipients. Methods: The associations between tacrolimus trough concentrations (C 0 ), non-trough concentrations (C 1 , C 2 , C 4 , C 6/8 ), and AUC 0)12 and the occurrence of hypertension, hyperkalaemia, hyperglycaemia and nephrotoxicity were assessed in 34 clinically stable liver transplant patients. Results and discussion: The most common adverse outcome was hypertension, prevalence of 36%. Hyperkalaemia and hyperglycaemia had a prevalence of 21% and 13%, respectively. A sequential population pharmacokinetic/pharmacodynamic approach was implemented. No significant association between predicted C 0 , C 1 , C 2 , C 4 , C 6/8 or AUC 0)12 and adverse effects could be found. Tacrolimus concentrations and AUC measures were in the same range in patients with and without adverse effects.
A pharmacodynamic investigation of tacrolimus in pediatric liver transplantation
Liver Transplantation, 2004
Although monitoring of tacrolimus blood concentrations is standard clinical practice following liver transplantation, a greater understanding of the relationship between trough concentrations and clinical outcome is required. The aim of this study was to perform a pharmacodynamic investigation of tacrolimus in pediatric liver transplant recipients. A retrospective analysis was performed on 35 pediatric liver recipients who received oral tacrolimus as the primary immunosuppressant. Outcome data were recorded corresponding to the times that tacrolimus trough concentrations had been determined (using a validated high-performance liquid chromatography-tandem mass spectrometry assay). A Mann-Whitney rank sum test was used to investigate differences between median concentrations at which drug toxicity, infection, and organ rejection did and did not occur. Outcome data and trough concentrations were recorded from the immediate posttransplant time to over 3
Clinical Transplantation, 2006
The calcineurin inhibitor tacrolimus has large inter-and intraindividual variations in its pharmacokinetics and optimal dose (1). Based on our experience with living donor liver transplantation (LDLT), the necessary dose of tacrolimus to reach and/or maintain the target blood level has a more than 10-fold difference between extreme cases. The reason for the remarkable difference among patients is not clear. Tacrolimus is, however, mainly metabolized by cytochrome P450 3A4 (CYP3A4) in the liver and intestine (2-4). Kishino et al. (5) reported that inter-and intraindividual variations in CYP3A4 activity were caused by differences in the actual ratio of graft volume to standard liver volume (GV/SV ratio) and donor age. Furthermore, Fukatsu et al. (6) reported that graft hepatic weight was significantly correlated with clearance of tacrolimus. One possible explanation for the high variability of the optimal tacrolimus dose and its pharmacokinetics is difference in graft size. In recent years, living donor liver transplantation in adult patients with small-for-size Kishino S, Ohno K, Shimanura T, Furukawa H, Todo S. A nomogram for predicting the optimal oral dosage of tacrolimus in liver transplant recipients with small-for-size grafts.
Transplantation Proceedings, 2005
Introduction. Jejunoileal bypass (JIB) was, at one time, a popular surgical technique for the treatment of morbid obesity. However, this operation was also associated with major complications. Consequently, many such procedures were eventually reversed. One of the most serious of these complications was liver failure. For those patients who developed cirrhosis, liver transplantation was one therapeutic alternative. Tacrolimus is one of the primary immunosuppressive agents used in liver transplantation. It is effective to prevent acute rejection episodes, but shows a narrow therapeutic index and can cause nephrotoxicity and neurotoxicity. This report describes the change in tacrolimus absorption that was observed after JIB reversal in a 57-year-old female liver transplant recipient.
Early metabolic treatment after liver transplant: amino acid tolerance
Intensive Care Medicine
We investigated the amino acid (AA) tolerance during Total Parenteral Nutrition (TPN) in adult patients undergone liver transplant (LTX). The treatment (Glucose and AA), induced on the 2nd postoperative day, was later maintained with 27 kcal/kg Ideal Body Weight (IBW) as glucose and 0.12 (12 patients: protocol #1), 0.18 (10 patients: protocol #2) and 0.25 g nitrogen (N)/kg IBW (13 patients: protocol #3) till end of the 6th postoperative day. The N intake was sequentially modified in protocol #2 and #3 to increase the supply of the amino acid (AA) that resulted in an infusion plasma level below the expected "normal" range (between 1 and 1.6 times the overnight fasting plasma level of volunteer). 35 consecutive adult patients without diabetes and organ failures for the entire study period. Plasma AA profile was measured before LTX and at the last TPN day under continuous infusion. During #1 and #2 protocol, many AA resulted below or at the lower range of the norm while, duri...
Metabolic effects of liver transplantation in cirrhotic patients
Journal of Clinical Investigation, 1997
To assess whether liver transplantation (LTx) can correct the metabolic alterations of chronic liver disease, 14 patients (LTx-5) were studied 5 Ϯ 1 mo after LTx, 9 patients (LTx-13) 13 Ϯ 1 mo after LTx, and 10 patients (LTx-26) 26 Ϯ 2 months after LTx. Subjects with chronic uveitis (CU) and healthy volunteers (CON) were also studied. Basal plasma leucine and branched-chain amino acids were reduced in LTx-5, LTx-13, and LTx-26 when compared with CU and CON (P Ͻ 0.01). The basal free fatty acids (FFA) were reduced in LTx-26 with respect to CON (P Ͻ 0.01). To assess protein metabolism, LTx-5, LTx-13, and LTx-26 were studied with the [1-14 C]leucine turnover combined with a 40-mU/m 2 per min insulin clamp. To relate changes in FFA metabolism to glucose metabolism, eight LTx-26 were studied with the [1-14 C]palmitate and [3-3 H]glucose turnovers combined with a two-step (8 and 40 mU/m 2 per min) euglycemic insulin clamp. In the postabsorptive state, LTx-5 had lower endogenous leucine flux (ELF) (P Ͻ 0.005), lower leucine oxidation (LO) (P Ͻ 0.004), and lower non-oxidative leucine disposal (NOLD) (P Ͻ 0.03) with respect to CON (primary pool model). At 2 yr (LTx-26) both ELF (P Ͻ 0.001 vs. LTx-5) and NOLD (P Ͻ 0.01 vs. LTx-5) were normalized, but not LO (P Ͻ 0.001 vs. CON) (primary and reciprocal pool models). Suppression of ELF by insulin (⌬-reduction) was impaired in LTx-5 and LTx-13 when compared with CU and CON (P Ͻ 0.01), but normalized in LTx-26 (P Ͻ 0.004 vs. LTx-5 and P ϭ 0.3 vs. CON). The basal FFA turnover rate was decreased in LTx-26 (P Ͻ 0.01) and CU (P Ͻ 0.02) vs. CON. LTx-26 showed a lower FFA oxidation rate than CON (P Ͻ 0.02). Tissue glucose disposal was impaired in LTx-5 (P Ͻ 0.005) and LTx-13 (P Ͻ 0.03), but not in LTx-26 when compared to CON. LTx-26 had normal basal and insulin-modulated endogenous glucose production. In conclusion, LTx have impaired insulin-stimulated glucose, FFA, and protein metabolism 5 mo after surgery. Follow-up at 26 mo results in (a) normalization of insulin-dependent glucose metabolism, most likely related to the reduction of prednisone dose, and, (b) maintenance of some alterations in leucine and FFA metabolism, probably related to the functional denervation of the graft and to the immunosuppressive treatment.
Unusual high dose of tacrolimus in liver transplant patient, a case report
Case We describe the case of a liver transplant patient who had great difficulty in reaching the desired trough blood levels despite the use of high dose tacrolimus. The patient was homozygous for the CYP3A5*3 allele. However, the respective donor carried the wild-type CYP3A5*1/*1 genotype. Regarding ABCB1 SNPs at exon 21 and 26, the patient showed the 2677GT and 3435CC genotypes. For the corresponding donor we observed the 2677GG and 3435CC wild-type genotypes. One, two and three weeks after transplantation the patient received daily 0.219, 0.287 and 0.273 mg/kg of tacrolimus, respectively. However, the corresponding tacrolimus trough blood levels were of 4.6, 5.6 and 6.1 ng/mL. The tacrolimus target level of 10.4 ng/mL was finally reached after 1 month of therapy. During the entire period of observation the kidney showed no sign of damage. No other signs of toxicity were reported except for the occurrence of an isolated systolic hypertension. Conclusions CYP3A5 genotyping may represent a useful tool to better evaluate the appropriate initial dose of tacrolimus for patients carrying a liver with the CYP3A5*1/*1 genotype. Keywords ABCB1 Á CYP3A5 Á Liver transplant Á Pharmacogenomics Á Single nucleotide polymorphisms Á Tacrolimus Á Trough blood levels Impacts on practice • In this report we describe the case of a liver transplant patient receiving a liver with a CYP3A5*1/*1 genotype who had great difficulty in reaching the desired blood tacrolimus levels despite the use of high doses of the immunosuppressive drug. • We call attention regarding the significance of pharmacogenomics especially for the readers involved in transplantation medicine.