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The objective of this study was to evaluate the safety and efficacy of adult-to-adult living donor liver transplantation, specifically donor outcomes. A systematic review, with searches of the literature up to January 2004, was undertaken. Two hundred and fourteen studies provided information on donor outcomes. The majority of these were case series studies, although there were also studies comparing living donor liver transplantation with deceased donor liver transplantation. Both underreporting and duplicate reporting is likely to have occurred, and so caution is required in interpretation of these results. Overall reported donor mortality was 12 to 13 in about 6,000 procedures (0.2%) (117 studies). Mortality for right lobe donors to adult recipients is estimated to be 2 to 8 out of 3,800 (0.23 to 0.5%). The donor morbidity rate ranged from 0% to 100% with a median of 16% (131 studies). Biliary complications and infections were the most commonly reported donor morbidities. Nearly all donors had returned to normal function by 3 to 6 months (18 studies). In conclusion, there are small, but real, risks for living liver donors. Due to the short history of adult-to-adult living donor liver transplantation, the long-term risks for donors are unknown. Liver Transpl 12: 24 -30, 2006.

The early prediction that the rate of injury during LC would decline substantially with increased experience has not been fulfilled. Bile duct injury that occurs at LC is of greater severity than with open cholecystectomy. Bile duct injury is recognized during LC in less than half the cases. Evidence is accruing that the use of cholangiography reduces the risk and severity of injury and, when correctly interpreted, increases the chance of recognition of bile duct injury during the procedure. Prevention is the key but, should an injury occur, referral to a specialist in biliary reconstructive surgery is indicated.

Tacrolimus, a cornerstone immunosuppressant, is available as a twice-daily formulation (tacrolimus bid). A once-daily prolonged-release formulation (tacrolimus qd) has been developed. This 6-week, randomized, phase 2, multicenter, open-label, prospective trial in primary liver transplant recipients investigated and compared the pharmacokinetics (PK) of tacrolimus for qd and bid formulations. All patients received tacrolimus-based immunosuppression (tacrolimus qd, n ¼ 67; bid, n ¼ 62). PK data were available for 77 patients (tacrolimus qd, n ¼ 45; bid, n ¼ 32). Tacrolimus area under the curve (AUC) from 0 to 24 hours (AUC 0-24 ) at equivalent doses was approximately 50% lower for tacrolimus qd than for bid on day 1 (146 versus 264 ngÁh/mL, respectively), but by day 14 was comparable between treatments (324 and 287 ngÁh/mL, respectively) with higher tacrolimus qd doses. There was a strong correlation between AUC 0-24 and concentration at 24 hours for tacrolimus qd and bid (r ¼ 0.92 and r ¼ 0.76, respectively). Furthermore, the relationship between these 2 parameters (ie, the slope of the line) was also similar for the 2 formulations. Efficacy endpoints were comparable for both formulations at 6 weeks with Abbreviations: AE, adverse event; AUC 0-24 , area under the curve from 0 to 24 hours; AZA, azathioprine; bid, twice daily; BPAR, biopsy-proven acute rejection; C 24 , concentration at 24 hours; C max , maximum concentration; C min , minimum blood concentration; MMF, mycophenolate mofetil; NEC, not elsewhere classified; PK, pharmacokinetics; qd, once daily; SD, standard deviation; T max , time to maximum concentration. This study and statistical analyses, and the editorial and project management services of Acumed involved in the preparation of this manuscript, were supported by Astellas Pharma Europe, Ltd., Staines, UK. L. Fischer, B. Gridelli, A. Roy, A. Vitale, A. Valdivieso, E. Varo, D. Seehofer, B. Ericzon, and K. Boudjema have declared no conflicts of interest. P. Trunečka has acted as study investigator and advisory board member for Astellas and has received speaker's fees. S. Lynch has received honoraria for chairing and speaking at international meetings for Astellas and JanssenCilag,

These results of the present study suggest that liver resection is an effective management option in selected patients with NCNN metastases confined to the liver.

Malnutrition is common in children with end-stage liver disease (ESLD) awaiting orthotopic liver transplantation (OLT), and nutritional support is assuming an important role in preoperative management. To evaluate preoperative nutritional therapy, 19 children (median age 1.25 y) with ESLD awaiting OLT were prospectively studied. Two high-energy, isoenergetic and isonitrogenous nutritional formulations delivered nasogastrically were compared: a branched-chain amino acid (BCAA)-enriched semielemental formulation and a matched standard semielemental formation. Twelve of 19 patients completed a randomized controlled study before OLT and 10 of 19 completed a full crossover study. Improvements in weight and height occurred during the BCAA supplements, with no statistical change on the standard formulation. Significant increases in total body potassium, midupper arm circumference, and subscapular skinfold thickness occurred during the BCAA supplements, whereas no significant changes occurred during the standard formulation period. Significantly fewer albumin infusions were required during the BCAA supplement. These findings suggest that BCAA-enriched formulas have advantages over standard semielemental formulas in improving nutritional status in children with ESLD, and are deserving of wider application and study.

T acrolimus, a potent immunosuppressive agent, has emerged as a valuable therapeutic alternative to cyclosporine after adult liver transplantation. 1 Similar to cyclosporine, tacrolimus has a narrow therapeutic window. 2 Continuous adequate immunosuppression is imperative for maintenance of the graft, whereas overimmunosuppression can lead to serious toxicities, infections, and increased risk for lymphoproliferative disease. It is not possible to give a standard dosing regimen to all adults and achieve concentrations within this narrow therapeutic range. Tacrolimus shows considerable interindividual and intraindividual variability in its pharmacokinetics, with poor correlation between drug dosage and blood concentrations. 2 These factors make defining an optimal dosing schedule for this agent difficult. 3 A number of studies have evaluated the pharmacokinetic properties of tacrolimus. 2 Oral bioavailability of this agent is generally low (ϳ25%), but can vary from 4% to 93%. Tacrolimus binds extensively to erythrocytes and, in plasma, to ␣1-acid glycoprotein and albumin. It is extensively metabolized by the cytochrome P-450 system and subject to P-glycoprotein countertransport. 4 Greater than 95% of tacrolimus is eliminated by the biliary route; renal excretion of the parent drug accounts for less than 1% of total body clearance.To date, the majority of pharmacokinetic studies in adult liver transplant recipients have used a classic approach to data generation. [5][6][7][8][9][10][11][12] Kinetic information has been obtained through multiple blood sampling in small relatively homogenous patient groups during a single dosing interval or during a short time span in the immediate posttransplantation period. Different factors that may alter drug pharmacokinetics have not been investigated simultaneously. Such studies provide little information on interindividual and intraindividual pharmacokinetic variability. Furthermore, kinetic information has been based on immunoassay analysis of tacrolimus blood samples. Such assays are not specific for the parent drug, with reports of significant and variable cross-reactivity of assay antibody with some tacrolimus metabolites. 3 Such assay techniques as liquid chromatography-tandem mass spectrometry

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