Transplant patients liver

Haddad EM, McAlister VC, Renouf E et al (2006) Cyclosporin versus tacrolimus for liver transplanted patients. Cochrane Database Syst Rev (4) CD005161... 

Hyperlipidemia is seen in up to 60% of heart, lung, and renal transplant patients and greater than 30% of liver transplant patients.64 66 As a result of elevated cholesterol levels, transplant recipients are not only at an increased risk of atherosclerotic events, but emerging evidence also shows an association between hyperlipidemia and allograft vasculopathy.66 Hyperlipidemia, along with other types of cardiovascular disease, is now one of the primary causes of morbidity and mortality in long-term transplant survivors.67... 

Drug absorption is highly variable in neonates and infants [21,22]. Older children appear to have absorption patterns similar to adults unless chronic illness or surgical procedures alter absorption. Differences in bile excretion, bowel length, and surface area probably contribute to the reduced bioavailability of cyclosporine seen in pediatric liver transplant patients [22a]. Impaired absorption has also been observed in severely malnourished children [22b]. A rapid GI transit time may contribute to the malabsorption of carbamazepine tablets, which has been reported in a child [23]. Selection of a more readily available bioavailable dosage form, such as chewable tablets or liquids, should be promoted for pediatric patients. 

These findings were confirmed by Paine et al. [28] who administered 1 mg midazolam intravenously (n = 5) or 2 mg intraduodenally (n = 5) to liver transplant patients during the time that the liver had been removed. Thus, only the gut wall... 

Svoboda-Newman SM, Greenson JK, Singleton TP, et al. Detection of hepatitis C by RT-PCR in formalin-fixed paraffin-embedded tissue from liver transplant patients. Diagn. Mol. Pathol. 1997 6 123-129. 

Liver transplant patients In liver transplant patients, there was a significantly higher incidence of tissue-invasive CMV disease in the valganciclovir-treated group compared with the oral ganciclovir group. Valganciclovir is not indicated for use in liver transplant patients. 

The plasma protein binding of tacrolimus is approximately 99%. Tacrolimus is bound mainly to albumin and alpha-1-acid glycoprotein and has a high level of association with erythrocytes. It is extensively metabolized by the mixed-function oxidase system, primarily the cytochrome P450 system (CYP3A). The disposition of tacrolimus from whole blood was biphasic with a terminal elimination half-life of 11.7 hours in liver transplant patients. 

Nephrotoxicity Tacrolimus can cause nephrotoxicity, particularly when used in high doses. Nephrotoxicity has been noted in approximately 52% of kidney transplantation patients and in 33% to 40% of liver transplantation patients receiving the drug. 

Coadministered grapefruit juice has been reported to increase tacrolimus blood trough concentrations in liver transplant patients. 

Mild nephrotoxicity occurs in 25% of renal transplant patients, 38% of cardiac transplant patients, and 37% of liver transplant patients, generally 2-3 mo after transplantation (more severe toxicity generally occurs soon after transplantation). Hepatotoxicity occurs in 4% of renal transplant patients, 7% of cardiac transplant patients, and 4% of liver transplant patients, generally within the first mo after transplantation. Both toxicities usually respond to dosage reduction. 

Mycophenolate mofetil, a semisynthetic derivative of mycophenolic acid, isolated from the mould PenicilUum glaucum is used in kidney and liver transplant patient. Another newer compound mizoribine is used in kidney transplantation. 

Gerster JC, Dudler M, Halkic N, Gillet M. Gout in liver transplant patients receiving tacrolimus. Ann Rheum Dis 2004 63(7) 894-5. 

The pharmacokinetic properties of the microemulsion were compared with those of the standard formulation in 39 liver-transplanted patients. AUC and Cmax values were significantly increased, and tmax was decreased following the microemulsion formulation, in both fasted and postprandial state. Differences between the microemulsion and the regular formulation in the fasting state and after high-fat meal, respectively, were +64% and +38% for AUC, +119% and +53% for Cmax, and -21% and —59% for tmax [43]. 

Nashan, B., Schlitt, H. J., Schwinzer, R. et al. (1996). Immunoprophylaxis with a monoclonal anti-IL-2 receptor antibody in liver transplant patients. Transplantation 61,546-554. 

Thummel KE, Shen DD, Podoll TD, et al. Use of midazolam as a human cytochrome P450 3A probe I. In vitro-in vivo correlations in liver transplant patients. J Pharmacol Exp Ther 1994 271 549-556. 

The other two diseases related to UGT1A1 are Crigler-Najjar (CN) syndrome types I and II. Many different mutations in UGT1A1 have been identified. CN type I patients express a mutated protein that is essentially devoid of activity. These patients therefore are unable to conjugate bilirubin. Until recently, this condition was lethal in childhood however, now these patients can be treated with phototherapy (discussed in the next section on Photobilirubin) and liver transplantation. Patients with CN type II express a mutated protein that retains some activity. These patients generally respond to phenobarbital, which increases the transcription of UGT1A1. Both CN types I and II are recessive disorders and rare. 

MELD and PELD are scoring systems often used as a method of prioritising patients awaiting liver transplantation. Patients with a higher score are deemed to require a transplant more urgently than those with a lower score. The MELD system is for patients 12 years and older and... 

Burckart GJ, Frye RF, Kelly P, et al. (1998) Induction of CYP2E1 activity in liver transplant patients as measured by chlorzoxazone 6-hydroxylation. Clin Pharmacol Ther 63 296-302. 

Pescovitz MD, Rabkin J, Merion RM, Paya CV, Pirsch J, Freeman RB et al. Valganciclovir results in improved oral absorption of ganciclovir in liver transplant patients. Antimicrob Agents Chemother 2000 44 2811-5. 

Thummelef al. (21) avoided the intrinsic variability of enzyme acctivity in the human population by predicting in vivo clearances from in vitro kinetic data in liver transplant patients. They were interested in using midazolam (MDZ) as a probe of CYP3A isoforms in the liver. Because biopsies were performed for the medical management of the transplant... 

FIGURE 30.13 Observed total elimination clearance (CLg) of midazolam (MDZ) in liver transplant patients versus hepatic clearance (CLjj) of 1 -OH MDZ predicted from biopsy specimens. The line is the predicted hepatic clearance of MDZ if the I -hydroxylation pathway accounts for 70% of the substrate loss. (Data from Thummel KE et al. J Pharmacol Exp Ther 1994 271 549-56.)... 

Miller, W.J., Federle, M.P., Campbell, W.L. Diagnosis and staging of hepatocellular carcinoma comparison of CT and sonography in 36 liver transplantation patients. Amer. J. Roentgenol. 1991 157 303-306... 

Melanosis coli occurred in a 39-year-old liver transplant patient who took an over-the-counter product containing aloe, rheum, and frangula (4). The typical brownish pigmentation of the colonic mucosa developed over 10 months. The medication was withdrawn and follow-up colonoscopy 1 year later showed normal looking mucosa. However, a sessile polypoid lesion was found in the transverse colon. Histology showed tubulovillous adenoma with extensive low-grade dysplasia. 

Meyers BR, Papanicolaou GA, Sheiner P, Emre S, Miller C. Tuberculosis in orthotopic liver transplant patients increased toxicity of recommended agents cure of disseminated infection with nonconventional regimens. Transplantation 2000 69(l) 64-9. 

Meyers B, Borrego F, Papanicolaou G. Pneumocystis carinii pneumonia prophylaxis with atovaquone in trimethoprim-sulfamethoxazole-intolerant orthotopic liver transplant patients a preliminary study. Liver Transpl 2001 7(8) 750-1. 

Neurological symptoms were observed in 12-25% of liver-transplant patients and in 29% of bone marrow transplant patients, but severe neurotoxicity occurred only in about 1% (18,19/21). They usually appeared within the first month of treatment, but were sometimes delayed (19). Particular attention should be paid to prompt recognition of severe neurotoxicity, because abnormalities of the white matter can occur. Patients usually improved rapidly after temporary ciclosporin withdrawal or dosage reduction, and tacrolimus has sometimes been used successfully instead (SEDA-21, 383) (18). However, recurrence of seizures and persistent electroencephalographic abnormahties were found in 46 and 70% of pediatric transplant patients respectively who had had ciclosporin acute encephalopathy and seizure syndrome and who were followed-up for 49 months (22). 

A possible consequence of bile acid abnormalities and cholestasis associated with ciclosporin is the development of cholelithiasis in liver transplant patients when the donor has pre-existing susceptibihty for cholesterol gallstone formation or abnormalities of bile composition. 

From the results of a retrospective study of 227 liver transplant patients who took Neoral as the primary immunosuppressant, it was suggested that this formulation may reduce the risk of severe neurotoxicity (210). Mild-to-moderate symptoms, that is headache (n = 24), mild hand tremor (n = 13), and paresthesia (n = 5), were the most frequent, whereas generalized seizures were reported in only two patients. 

Faure JL, Causse X, Bergeret A, Meyer F, Neidecker J, Paliard P. Cyclosporine induced hemolytic anemia in a liver transplant patient. Transplant Proc 1989 21(1 Pt 2) ... 

Monegal A, Navasa M, Guanabens N, Peris P, Pons F, Martinez de Osaba MJ, Rimola A, Rodes J, Munoz-Gomez J. Bone mass and mineral metabolism in liver transplant patients treated with FK506 or cyclosporine A. Calcif Tissue Int 2001 68(2) 83-6. 

Tullock W, Scott V, Smith DA, Phillips L, Cook DR. Kinetics/dynamics of 51W89 in liver transplant patients and in healthy patients. Anesthesiology 1994 81 A1076. 

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