Synergistic suppression of pre-perfusion of donor livers with recipient serum and cobra venom factor treatment on hyperacute rejection following liver xenotransplantation.

PURPOSE: To investigate synergistic suppression of donor liver pre-perfusion with recipient serum (RS) and cobra venom factor (CVF) treatment on hyperacute rejection (HAR) following liver xenotransplantation. METHODS: Guinea-pigs (GP, n=24) and Sprague-Dawley rats (SD, n=24) were recruited. Before transplantation, serum was collected from SD rats and used for preparation of inactivated complements. GP and SD rats were randomly assigned into four groups (n=6), respectively: RS group, CVF group, RS+CVF group and control group. Orthotopic liver xenotransplantation was performed with modified two-cuff technique. The survival time and liver function of recipients, morphological and pathological changes in rat livers were investigated. RESULTS: There was no piebald like change in the recipient livers in all experiment groups. The survival time of recipients in all experiment groups was longer than that in control group (p<0.05). Moreover, the survival time in the RS+CVF group was markedly longer than that in the RS group (p<0.01) and CVF group (p<0.05). The serum ALT level in all experiment groups were lower than that in the control group (p<0.05). Furthermore, the ALT level in the RS+CVF group was significantly lower than that in the CVF group (p<0.05) and RS group (p<0.01). The histological damages were significantly improved when compared with the control group, and the histological damages in the RS+CVF group were milder than those in the remaining groups (p<0.05) CONCLUSION: Pre-perfusion of donor liver with recipient serum and cobra venom factor treatment can exert synergistic suppressive effects on the hyperacute rejection following liver xenotransplantation.

Synergistic suppression of pre-perfusion of donor livers with recipient serum and cobra venom factor treatment on hyperacute rejection following liver xenotransplantation / Supressão sinérgica da rejeição hiperaguda no xenotransplante hepático com uso da pre-perfusão dos fígados doadores tratados com soro do receptor e com fator veneno de cobra

PURPOSE: To investigate synergistic suppression of donor liver pre-perfusion with recipient serum (RS) and cobra venom factor (CVF) treatment on hyperacute rejection (HAR) following liver xenotransplantation. METHODS: Guinea-pigs (GP, n=24) and Sprague-Dawley rats (SD, n=24) were recruited. Before transplantation, serum was collected from SD rats and used for preparation of inactivated complements. GP and SD rats were randomly assigned into four groups (n=6), respectively: RS group, CVF group, RS+CVF group and control group. Orthotopic liver xenotransplantation was performed with modified two-cuff technique. The survival time and liver function of recipients, morphological and pathological changes in rat livers were investigated. RESULTS: There was no piebald like change in the recipient livers in all experiment groups. The survival time of recipients in all experiment groups was longer than that in control group (p<0.05). Moreover, the survival time in the RS+CVF group was markedly longer than that in the RS group (p<0.01) and CVF group (p<0.05). The serum ALT level in all experiment groups were lower than that in the control group (p<0.05). Furthermore, the ALT level in the RS+CVF group was significantly lower than that in the CVF group (p<0.05) and RS group (p<0.01). The histological damages were significantly improved when compared with the control group, and the histological damages in the RS+CVF group were milder than those in the remaining groups (p<0.05) CONCLUSION: Pre-perfusion of donor liver with recipient serum and cobra venom factor treatment can exert synergistic suppressive effects on the hyperacute rejection following liver xenotransplantation.

OBJETIVO: Investigar a supressão sinérgica da pré-perfusão do doador de fígado com soro do receptor (SR) e tratamento com fator veneno de cobra (FVC) na rejeição hiperaguda (RHA) após o xenotransplante de fígado. MÉTODOS: Foram utilizados Cobaias (GP, n=24) e ratos Sprague-Dawley (SD, n=24). Antes do transplante foram coletadas amostras de soro dos ratos SD e usados para a preparação dos complementos inativados. Cobaias GP e ratos SD foram randomicamente distribuídos em quatro grupos (n=6), respectivamente: grupo RS, grupo FVC, grupo SR+FVC e grupo controle. Xenotransplante ortotópico do fígado foi realizado com a técnica de dois cuffs modificados. Foram investigados o de tempo de sobrevida, a função hepática dos receptores e alterações morfopatológicas em fígados de ratos. RESULTADOS: Não houve alteração na coloração do parênquima dos fígados nos receptores. O tempo de sobrevida dos receptores em todos os grupos experimentais foi mais longo do que o grupo controle (p<0,05). Além disso, o tempo de sobrevida do grupo SR+ FVC foi marcadamente maior do que o grupo SR (p<0,01) e o grupo FVC (p<0,05). O nível sérico ALT foi menor em todos os grupos experimentais do que o grupo controle (p<0,05). O nível de ALT no grupo SR+ FVC foi significantemente menor do que no grupo FVC (p<0,05) e o grupo SR (p<0,01). As alterações histológicas foram significantemente melhoradas quando comparado com o grupo controle, e os danos histológicos no grupo SR+ FVC foram mais moderados do que nos grupos restantes (p<0,05). CONCLUSÃO: Pré-perfusão do fígado doador com soro do receptor e fator veneno de cobra pode exercer efeito supressor sinérgico da rejeição hiperaguda após xenotransplante de fígado.

Supplementation of amino acids to prevent reperfusion injury after liver surgery and transplantation--where do we stand today?

BACKGROUND & AIMS: Functional liver failure remains one of the major complications after liver surgery. Ischemia/reperfusion injury (IRI) is strongly associated with increased morbidity and mortality after liver resection and transplantation. An ischemia induced activation of Kupffer cells with subsequent release of toxic mediators leads to disturbance of intrahepatic microcirculation, increased oxygen consumption of the liver and depletion of hepatic glycogen reserves. Aim of this review was to summarize the evidence for prevention of IRI by amino acid supplement and to give an overview on potential clinical use in liver surgery. METHODS: A systematic literature search (Medline, Embase, and The Cochrane Central Register of Controlled Trials) was performed to identify the relevant literature. RESULTS: Amino acid supplement has hepatoprotective effects and is non-toxic. Up to now heterogenic results have been reported from clinical trials. However, positive effects on microcirculation, leukoycte-endothelial interaction, Kupffer cells and pro-inflammatory mediator release have been described in trials investigating glycine supplementation. The data for N-acetylcysteine remain heterogenic. CONCLUSION: An effective protection against IRI by amino acid supplementation has been demonstrated in experimental and several clinical studies. However, further clinical trials are warranted to identify the most promising approach for a routine clinical application.

A case of recurred hepatocellular carcinoma refractory to doxorubicin after liver transplantation showing response to herbal medicine product, Rhus verniciflua Stokes extract.

There is no established protocol proven to be beneficial for treatment of hepatocellular carcinoma recurrence after liver transplantation. Only a few reports have shown direct treatment by surgery or ablation to be independent predictors of survival for localized recurrence. Moreover, the necessity of immunosuppression to prevent allograft rejection makes many physicians hesitate to administer systemic chemotherapy. This case report documents a case in which the administration of an herbal product, an extract of the lacquer tree, Rhus verniciflua Stokes, was associated with a decrease in the size of lung metastases in a patient with recurrent hepatocellular carcinoma after liver transplantation refractory to doxorubicin. This patient experienced prolonged survival compared with average survival times and little toxicity.

Hepatoprotective effects of marine and kuhuang in liver transplant recipients.

We aimed to assess the effects of traditional Chinese medicine; marine (MT) and kuhuang (KH), either alone or in combination, on the early graft function of the recipients and overall patient survival rate after liver transplantation (LT) by using diammonium glycyrrhizinate (DG) as a positive control. A total of 151 subjects undergoing LT were included in this prospective study. According to the different regimens given in the first two post-transplant weeks, they were divided into DG group (n = 49), DG + KH group (n = 36), MT group (n = 42) and MT + KH group (n = 24). The graft function in the early post-transplant period and patient survival rate were examined. During the first two post-transplant weeks, there was no significant difference in total bilirubin, alanine transaminase, aspartate transaminase, serum creatinine, and prothrombin time between MT group and DG group. Patient survivals in these two groups were also similar. Compared to DG group, DG + KH group showed a significantly lower total bilirubin value on post-transplant day 5 (3.2 +/- 2.1 mg/dL vs. 5.7 +/- 5.6 mg/dL, p < 0.01) and day 7 (2.8 +/- 1.8 mg/dL vs. 5.8 +/- 6.1 mg/dL, p < 0.01), and higher patient survival. There was no significant difference between DG + KH group and MT + KH group. In conclusion, MT provides an alternative to DG after LT. The combination of MT and KH is highly effective in decreasing the total blirubin in the early post-transplant period and improving patient survival.

Effect of N-acetylcysteine administration on intraoperative plasma levels of interleukin-4 and interleukin-10 in liver transplant recipients.

We investigated whether intraoperative administration of N-acetylcysteine (NAC) in liver transplant recipients ameliorated their inflammatory responses by increasing intraoperative plasma levels of interleukin (IL)-4 and IL-10. This prospective, randomized, double-blind clinical trial included liver transplant recipients randomly assigned to the NAC-treated (n = 25) or the placebo (n = 25) group. The NAC-treated group received 100 mg/kg dissolved in 5% dextrose over 15 minutes during the anhepatic phase, followed by a continuous infusion of 50 mg/kg in 5% dextrose over the next 24 hours, whereas the placebo group received equal amounts of 5% dextrose solution during the same time. Peripheral blood samples were drawn in EDTA-containing tubes after induction of anesthesia (I-1); at 15 minutes into the anhepatic phase (I-2) prior to the administration of NAC or placebo; at 5 minutes before reperfusion (I-3); at 10 minutes after reperfusion (I-4); at 20 minutes after reperfusion (I-5); at 60 minutes after reperfusion (I-6); and at 1 hour after completion of the liver transplantation (I-7). Cytokine levels were determined using a technique which combined enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Plasma IL-4 levels were significantly higher among the NAC-treated group than the placebo group at I-3 (P = .046) and I-4 (P = .041). Plasma IL-10 levels showed significant enhancement in the NAC-treated group at 5 minutes before reperfusion (I-3; P = .007). We concluded that intraoperative NAC administration during the anhepatic phase of liver transplantation significantly increased recipient IL-4 plasma levels before and after reperfusion, and IL-10 plasma values before reperfusion (I-3). These enhancements seemed to be associated with a protective effect against reperfusion injury.

Timing for orthotopic liver transplantation in children with biliary atresia: a single-center experience.

INTRODUCTION: Biliary atresia is the most common indication for orthotopic liver transplantation (OLT) in childhood. The purpose of this study was to determine predictive prognostic factors for children with biliary atresia related to the timing for OLT within 15 months after hepatoportoenterostomy (HPE). PATIENTS AND METHODS: We retrospectively analyzed the medical records of 25 children (7 boys and 18 girls) who underwent HPE because of biliary atresia between January 1990 and December 2005 at our center. Data examined included age and pathologic findings at HPE, Pediatric End-Stage Liver Disease score at first admission, whether phototherapy was given, liver function test results and total bilirubin level before and 30 days after HPE, and number of cholangitis events. RESULTS: Twelve children were alive with their native liver, 8 had undergone living donor OLT (all children alive), and 5 had died without OLT. Five- and 10-year survival rates without OLT after HPE were 47.4% and 26.3%, respectively. At univariate analysis, the predictive prognostic factors for children with biliary atresia were total bilirubin level at 30 days after HPE and Pediatric End-Stage Liver Disease score before HPE. At multivariate analysis, the only prognostic factor was total bilirubin level at 30 days after HPE. CONCLUSIONS: In this study, the predictive prognostic factor was total bilirubin level at 30 days after HPE. Orthotopic liver transplantation within 15 months after HPE is needed in children with biliary atresia with a high total bilirubin level at 30 days after HPE.

Retrograde oxygen persufflation preservation of human livers: a pilot study.

Retrograde oxygen persufflation as a supplement of cold storage during the preservation period has the potential to better utilize ischemically damaged marginal livers in the experimental setting. Retrograde oxygen persufflation was applied in selected livers to demonstrate feasibility in the clinical setting and to investigate potential beneficial effects. Between 4/04 and 3/05 5 marginal otherwise discarded livers with warm ischemic damages from deceased donors (age 52 [37-64]) were accepted for transplantation. All organs were distantly procured and shipped to our center. Immediately after arrival, filtered humidified gaseous oxygen was given via the hepatic veins for at least 60 minutes with a pressure up to 18 mm mercury. Liver biopsies were analyzed for ATP content before and after persufflation. All patients (age 55 [46-66]) survived without retransplantation, had good initial function and are alive and well after minimum follow-up of two years. Bleeding from pinpricks stopped spontaneously after 5-10 minutes after reperfusion but was prolonged in one patient with severe coagulopathy until correction. One patient developed arterial thrombosis at postop day 0. He fully recovered after thrombectomy. Another patient developed subcapsular hematoma, which was removed at postop day 10. On routine postoperative biopsies vascular structures appeared undamaged. ATP levels in pre-reperfusion biopsies revealed a more than twofold increase of ATP content compared to biopsies before persufflation. Retrograde oxygen persufflation preservation is feasible and save in the clinical setting, improves early aerobic metabolism and therefore potentially improves primary organ function after liver transplantation.

The possible study of HuaXi-1 solution for all intra-abdominal organ preservation: a study in rats.

OBJECTIVE: University of Wisconsin (UW) solution continues to be the most commonly used solution for intra-abdominal organs. However, it is expensive. Therefore, we have formulated HuaXi-1 (HX-1) solution. The aim of this research was to assess the effect of HX-1 solution compared to UW, Collins 2, and hypertonic citrate solutions on intra-abdominal organs. METHODS: The effects of HX-1 solution for all intra-abdominal organ preservation were studied in a noncirculated, isolated, perfused rat liver model, in rat pancreas isografts in diabetic rats, and in a kidney autotransplant model. The effects were investigated by measuring hepatic tissue water content, sinusoidal lining cell mortality, Krebs-Henseleits perfusate, aspartate aminotransferase, the number of livers secreting bile during isolated perfusion, blood glucose, glucose tolerance tests, serum insulin of the rat pancreas-transplant recipients, the maximum serum creatinine levels, kidney graft survival rates, and observing the morphological changes in liver, pancreas, and kidneys. RESULTS: HX-1 solution preserved rat liver well for 24 hours as effectively as UW, rat pancreas as well for 48 hours, and dog kidney as well for 72 hours. CONCLUSION: The experimental findings indicated that HX-1 solution was effective to preserve all intra-abdominal organs; it may simplify cold storage of organs for transplantation.

Effect of chronic glucocorticoid therapy and the gender difference on bone mineral density in liver transplant patients.

BACKGROUND: Chronic glucocorticoid therapy (CGT) has been shown to result in bone density loss causing osteoporosis. Patients undergoing liver transplantation (LT) are on CGT and are at increased risk for bone disease. To further study the relationship between CGT and bone loss, we analyzed the bone mineral density (BMD) in relation to the cumulative dose of CGT in patients who had undergone LT. MATERIALS AND METHODS: We retrospectively collected information on 57 patients who underwent LT more than 1 year ago, which included demographics, cumulative CGT dose, BMD and t-scores of the femur/lumbar vertebra as measured by dual-energy X-ray absorptiometry (DEXA) for 1 and 2 years post-transplant. Patients receiving CGT >3500 mg/1st year were compared with CGT <3500 mg the first year. The group consisted of 75% males and 25% females. RESULTS: Data showed that all patients on CGT had a moderately increased risk of fracture one year post-transplant. In the high dose group, females had significantly worse femur BMD and t-scores that persisted through the second year. This difference was not seen in the low dose group. CONCLUSION: We found that all liver transplant patients on CGT have an increased risk of bone disease and that female patients receiving CGT >3500 mg the first year have a much higher risk of bone disease than males and that this risk persists during the second year. Because most of the steroids are given during the 1st month post-transplant, the amount of steroids given in this time period dictates the patients' risk for the subsequent 2 years.

Beneficial effect of liver transplantation on bone mineral density in small infants with cholestasis.

Reports of bone mineral density in children after liver transplantation are few. Eleven cholestatic children were analyzed before and 6 months after liver transplantation. No changes in serum levels of calcium, alkaline phosphates, or 25OHD were observed before versus after LTx. The serum levels of phosphorus and 1-25(OH)2D3 as well as total bone mass density and Cole index were significantly increased after liver transplantation.

Gene expression of cytochromes P450 in liver transplants over time.

OBJECTIVE: The aim of this study was to (a) quantify the gene expression of some cytochromes P(450) (CYP), especially CYP3A4, in serial biopsies from liver grafts the first year after orthoptic liver transplantation (OLT) and (b) study the relationship between hepatic CYP3A4 gene expression and plasma levels of cyclosporine and tacrolimus. METHODS: Liver tissue was obtained from surplus material of routine liver biopsies performed in 20 patients during the first year after OLT. Real-time reverse-transcription polymerase chain reaction was used for quantitative analyses of mRNA specific for CYP3A4, CYP3A5, CYP2E1 and CYP1A2 cytochromes as well as P-glycoprotein (P-gp). The gene expression of beta-actin was used as an internal standard for comparisons between samples. RESULTS: The median value of the mRNA for all cytochromes, but not for P-gp, was found to increase significantly over time. The gene expression of CYP3A5, CYP2E1 and CYP1A2 was higher than that of CYP3A4. The gene expression of CYP3A4 was related to the plasma concentration of cyclosporine and tacrolimus, i.e. low mRNA concentrations corresponded to high serum concentration levels and vice versa. The serum concentration of bilirubin or the prothrombin index did not correlate with the gene expression level of the cytochromes. CONCLUSION: The hepatic mRNA expression of CYP3A4 and the other investigated cytochromes increased during the first year after OLT. This was not the case with P-gp. Low CYP3A4 gene expression was related to high plasma levels of cyclosporine and tacrolimus and vice versa.

Outcome of infections caused by multiple drug-resistant bacteria in liver transplant recipients.

OBJECTIVE: To evaluate the impact of infections caused by multiple-drug-resistant (MDR) bacteria on the clinical outcome of liver transplant recipients. METHODS: Retrospective study including all episodes of bacterial infection diagnosed in patients undergoing liver transplantation from January 19, 1999, to June 30, 2002. The diagnosis of bacterial infection required microbiological documentation. Mortality associated with episodes of infection by MDR bacteria was compared to that observed after antibiotic-susceptible bacterial infections. RESULTS: Among 99 patients undergoing liver transplantation during the study period, there were 57 episodes of bacterial infections. Gram-negative bacilli were the predominant etiologic agents (76%) and Pseudomonas aeruginosa was the most frequent bacterial species found in these cases (23 isolates, 28%). Thirty-six episodes of infection (63%) were caused by MDR bacteria. Mean time after transplantation to the diagnosis of infection was 17 days. Mortality associated with episodes of MDR bacterial infections (nine deaths, 25%) was not significantly different from that observed during episodes of antibiotic-susceptible bacteria (five deaths, 24%; P =.92). CONCLUSION: These data suggest that resistance to multiple antimicrobial agents does not have an impact on the mortality associated to bacterial infections in liver transplant recipients.

Matrine protects sinusoidal endothelial cells from cold ischemia and reperfusion injury in rat orthotopic liver transplantation.

The effect of matrine on cold ischemia and reperfusion injury of sinusoidal endothelial cells (SEC) was investigated in rats using an orthotopic liver transplantation (OLT) model. Syngeneic Sprague-Dawley (SD) rats were randomly assigned to 4 groups of 32 rats: untreated group (controls), low-dose treated group, high-dose treated group, and sham operation group (normals). After 5 hr of preservation in Ringer's solution, orthotopic implantation of the donor liver was performed. At 1, 2, 4, and 24 hr after reperfusion, 6 rats from each group were killed to collect blood and to excise the median hepatic lobe; the other 8 rats were observed to assess the 1-wk survival rate post-transplantation. All transplant recipients in the untreated group (controls) died within 48 hr, mostly between 10 to 20 hr. Matrine treatment increased the 1-wk survival rate to 75% in both treated groups. Plasma levels of hyaluronic acid (HA) at 1, 2, and 4 hr post-implantation were decreased significantly by matrine treatment. The immunohistochemical expression of intercellular adhesion molecule-1 (ICAM-1) in rat liver decreased significantly in both treated groups, and the pathological changes of SEC were ameliorated. Matrine markedly inhibited the activation of Kupffer cells and their release of tumor necrosis factor (TNF). Hepatic malondialdehyde (MDA) levels and superoxide dismutase (SOD) activities were improved by matrine administration. In conclusion, matrine can protect SEC from cold ischemia and reperfusion injury after rat orthotopic liver transplantation.

Effect of 1,25-dihydroxyvitamin D3 on preventing allograft from acute rejection following rat orthotopic liver transplantation.

AIM: To study the mechanism and the preventive role of 1,25-dihydroxyvitamin D3 in acute rejection following orthotopic liver transplantation. METHODS: Rats were randomly divided as donors or recipients for orthotopic liver allotransplantation model. Four groups were designed in the study, Group I: syngenic control (Wistar to Wistar); Group II: acute rejection (SD to Wistar); Group III: acute rejection treated with cyclosporine A, and Group IV: acute rejection treated with 1,25-(OH)2D3. Liver function, rejection activity index and mRNA of IFN-gamma, IL-10 in intragraft in recipients were measured in on day 1, 5, 7, 15, 30 posttransplant for assessing graft function, severity of acute rejection and immune state of recipients. RESULTS: Survival time of recipients in Group VI was significantly prolonged (over 100 days) in comparison with other groups (vs Group II, P<0.001; vs Group III, P>0.05). After treatment with 1,25-(OH)2 D3, mean value of all the assay tested on each experimental time was compared, liver function in group IV was significantly improved (AST 127+/-41 U/L-360+/-104 U/L, BIL 13+/-5 mmol/l-38+/-11 mmol/l; vs Group II, P<0.05; vs Group III, P>0.05. Rejection activity index was significantly decreased (0-3.3+/-1.6; vs Group II, P<0.05; vs Group III, P>0.05). Level of hepatic IFN-gamma mRNA in group IV was decreased, while level of hepatic IL-10 mRNA was increased (vs Group II, P<0.05; vs Group III, P>0.05). CONCLUSION: Our results indicated that 1,25-(OH)2D3 induced the secretion of cytokine toward to Th2 type, which would alleviate acute rejection, protect liver function and prolong survival of recipient after orthotopic liver transplantation.

Effect of hepatic artery flow on bile secretory function after cold ischemia.

These studies evaluated the influence of hepatic arterial flow on biliary secretion after cold ischemia. Preparation of livers for transplantation or hepatic support impairs biliary secretion. The earliest indication of cold preservation injury during reperfusion is circulatory function. Arterial flow at this time may be critical for bile secretion. Porcine livers were isolated, maintained at 4 degrees for 2 h and connected in an extracorporeal circuit to an anesthetized normal pig. The extracorporeal livers were perfused either by both the hepatic artery and portal vein (dual) or by the portal vein alone (single). Incremental doses of sodium taurocholate were infused into the portal vein of both the dual and single perfused livers, and the bile secretion was compared. Most endogenous bile acids are lost during hepatic isolation. After supplementation, the biliary secretion of phosphatidyl choline and cholesterol was significantly better in the dual than single vessel-perfused livers; however, no difference was seen in bilirubin output. Single perfused livers were completely unable to increase biliary cholesterol in response to bile acid. The dependence of bile cholesterol secretion on arterial flow indicates the importance of this flow to the detoxification of compounds dependent on phosphatidyl choline transport during early transplantation.

Long-term nutritional outcome after pediatric intestinal transplantation.

BACKGROUND/PURPOSE: The aim of this study was to describe the long-term nutritional status of a large population of children after intestinal transplantation and to identify factors associated with nutritional outcomes. METHODS: Longitudinal anthropometric data are maintained in a database registry for all patients referred to our Intestinal Care Center (ICC). Z-scores for weight and height were calculated biannually over a maximum of 2 years, and associations between baseline and follow-up laboratory measures and growth were evaluated for patients greater than 6 months post intestinal transplant. RESULTS: Since the inception of the ICC in December 1996, 24 pediatric patients (18 boys, 18 white) received an isolated small bowel or small bowel/liver transplant (median age, 3.2 years). The majority of cases (75%) had been diagnosed with surgical short bowel syndrome and were dependent on total parenteral nutrition (TPN) at the time of transplant. Of the 23 patients who survived the initial postoperative period, 87% were weaned from TPN to an amino-acid or peptide-based enteral formula or solid food within 3 months. A positive trend in z-scores for weight and height/length was observed in only 30% and 26% of patients, respectively, during the follow-up period. Although mean albumin levels increased significantly from 2.8 to 3.1 mg/dl by 6 months posttransplant (P <.01) no difference in alkaline phosphatase was found over time. Steroid doses were weaned within 3 to 4 months after transplantation but not discontinued. The cumulative survival rate was 91% at 1 year and 86% at 2 years posttransplant, whereas those weaned from TPN achieved 100% and 94% survival, respectively. CONCLUSIONS: Attainment of positive linear growth remains a challenge in the pediatric transplant population despite successful liberation from TPN, protein anabolism, and high survival rates. Further investigation into alternative methods of nutritional evaluation and manipulation as well as the use of growth factors to enhance the growth process need to be investigated.

[Effect of glycogen on calcium of donor liver during ischemia-reperfusion period].

OBJECTIVE: To evaluate the effect of glycogen on calcium concentration of rabbit donor liver during ischemia-reperfusion period. METHODS: Donor group (n=21) was divided into 3 subgroups randomly: Group A (n=7): fasting for 24 hours before harvesting; Group B (n=7): normal laboratory chew; Group C (n=7): normal laboratory chew plus glucose supplement intravenously. Based on the self-created animal model for ischemia-reperfusion, the levels of glycogen content, ATP level, viability of Ca(2+)ATPase and plasmic free Ca(2+) concentration ([Ca(2+)]i) of liver tissue were measured. RESULTS: Before cold preservation, there was a significant difference of glycogen content among the three groups at all time points except at the end of rewarming period. ATP level and Ca(2+)ATPase viability were significantly higher in group C than in other two groups. But the plasmic free Ca(2+) concentration was lower in groups with higher glycogen content. CONCLUSIONS: Donor liver with high glycogen content can provide relatively sufficient ATP, maintain better Ca(2+)ATPase viability and prevent plasmic free Ca(2+) concentration overloading. This maybe an important mechanism for glycogen to ameliorate ischemia-reperfusion injury to the donor livers.

Right lateral sector graft in adult living-related liver transplantation.

BACKGROUND: A major concern regarding adult living-related liver transplantation (LRLT) is graft-size disparity. The authors report their experience with LRLT using the right lateral sector. PATIENTS AND METHODS: Between January 2000 and April 2001, 32 adult-to-adult LRLTs were performed at our institution. Of these, six patients received a right lateral sector (RLS, segments VI and VII according to Couinaud's nomenclature for liver segmentation) graft. The right liver was over 70% of the estimated volume of the whole donor liver. The estimated RLS volume was greater than that of the left liver, which was over 40% of the recipient's standard liver volume. RESULTS: The postoperative course was uneventful in all donors. All of the patients survived the operation. Three patients were complicated with bile leakage from the dissection plane of the graft. Four patients suffered from acute rejection. CONCLUSIONS: RLS graft obtained by this procedure may be useful for overcoming borderline graft-recipient size differences and expanding the donor pool.

Serum osteoprotegerin levels in patients after liver transplantation and correlation to bone turnover, bone mineral density and fracture status.

The aim of this cross sectional study was to evaluate the prevalence of osteoporosis, vertebral fracture status and possible risk factors of bone loss including serum osteoprotegerin, a novel key regulator of osteoclast proliferation and activity in the posttransplantation period. We investigated 15 patients (10 male, 5 female) 20 +/- 6 (SE) months after orthotopic liver transplantation (OLT). All patients received immunosuppressive therapy and non were on calcium and/or vitamin D supplements at the time of admission to our osteoporosis outpatient clinic. Examinations included a bone densitometry measurement at the femoral neck, a standardized spinal X-ray and a morning blood sample. According to WHO criteria, osteoporosis at the femoral neck was present in 67% (10/15) of the patients with a mean T-score of -2.55 +/- 0.35. Vertebral fractures were seen in 33% and the mean number of fractures was 2.4 per patient. Secondary hyperparathyroidism (33%), vitamin D deficiency (53%) as well as impaired renal function (47%) were frequent findings in the patients. Low serum calcium was associated with elevated PTH- (r = -0.75, p = 0.001), serum cross laps- (r = -0.61, p = 0.01), osteocalcin levels (r = -0.49, p = 0.05), was an independent predictor of femoral neck bone mass (r = 0.57, p = 0.02) and accounted for 36% of this variance. Similarly, serum magnesium levels were also independently correlated to femoral neck Z-scores (r = -0.68, p = 0.0005). Two-thirds of the patients had elevated serum cross-laps, osteocalcin and bone specific alkaline phosphatase levels reflecting increased bone turnover. Serum osteoprotegerin (OPG) in liver transplant recipients was not significantly different when compared to healthy, matched controls (84.7 +/- 6.6 vs. 97.3 +/- 9.4 pg/ml, p = 0.50) and similar when fractured/non-fractured or osteoporotic/non-osteoporotic patients were compared. Serum OPG was, however, significantly correlated to serum cross laps (r = 0.71, p = 0.003), osteocalcin (r = 0.63, p = 0.01), serum parathyroid hormone (r = 0.61, p = 0.01) and serum creatinine levels (r = 0.53, p = 0.04) and showed only a weak and non-significant correlation to femoral neck Z-scores (r = -0.38, p = 0.16). Multiple regression analysis revealed that serum OPG was correlated independently of PTH, serum calcium and creatinine to serum cross-laps concentrations (r = 0.63, p = 0.04). In summary, we found a high prevalence of osteoporosis and vertebral fractures in liver transplant recipients with many of the patients showing evidence of vitamin D deficiency, secondary hyperparathyroidism and accelerated bone turnover. We conclude that secondary hyperparathyroidism and possibly serum magnesium seems to contribute significantly to the changes in bone mass during the posttransplantation period. Serum OPG was not correlated to bone mass or fracture status in this cross sectional setting but was elevated together with other bone resorption and -formation markers.