Living-related Liver Transplantation Recipients Research Articles

Liver Volume Restoration and Hepatic Microarchitecture in Small-for-Size Syndrome.

We investigated preoperative parameters that could work as markers of liver regeneration (LR), and tried to create an algorithm for therapeutic decision-making, looking at the clinical setting of post-hepatectomy liver failure (PHLF) after major liver resection for malignancies (LRM) and of the small-for-size syndrome (SFSS) after adult-to-adult living related liver transplantation (LRLT), considering PHLF and SFSS a single clinical entity. The clinical data of 2 series of 10 consecutive patients who experienced liver-specific complications after LRLT or LRM between 2008 and 2013 were analyzed. LR was evaluated by multidetector computed tomography (MDCT) and hepatic parenchymal findings with specific re-examinations of liver biopsies. The analysis was done according to demographics, tumor characteristics, and postoperative complications occurring within 90 days of surgery and codified within the Clavien classification. A total of 13 cases of SFSS occurred in 8 LRLT recipients (61.5%) and in 5 patients after LRM (38.5%). The incidence of SFSS was significantly associated with a greater spleen volume/future remnant liver volume ratio (1.08±0.5; P=0.02) and a reduced number of hepatic tumors (0.58±0.6; P=0.04). A greater degree of LR was not associated with a lesser likelihood of developing SFSS (P=0.31). SFSS incidence and re-examination of post-operative liver biopsies differed according to the evidence of focal endothelial denudation in the portal vein and centrilobular hepatocanalicular cholestasis. We found an association between SFSS incidence and the immunohistochemical overexpression of cytological proliferation marker Ki-67 (29.3±29.8%; P=0.007), which was a significant predictor of poor post-operative survival (OR=1.12, C.I.: 1.013; 1.242). SFSS is a rare but dangerous clinical entity characterized by anarchic hepatic regeneration. We suggest focusing on early diagnosis in order to establish non-surgical modulation of the portal inflow, in conjunction with optimization of medical management.

Performance of gadoxetic acid‐enhanced MRI for detecting hepatocellular carcinoma in recipients of living‐related‐liver‐transplantation: Comparison with dynamic multidetector row computed tomography and angiography‐assisted computed tomography

To clarify the diagnostic performance of gadoxetic acid-enhanced MRI for the detection of hepatocellular carcinoma (HCC) in recipients of living related-liver transplantation (LRLT). This retrospective study group consisted of 15 patients with 61 HCCs who each underwent multidetector row computed tomography (MDCT), gadoxetic acid-enhanced MRI, and angiography-assisted computed tomography (CT) before LRLT. The three modalities were compared for their ability to detect HCC. Two blinded readers independently reviewed the images obtained by each modality for the presence of HCC on a segment-by-segment basis using a 5-point confidence scale. The diagnostic performance of the modalities was evaluated in a receiver operating characteristic (ROC) analysis. The area under the ROC curve (Az), sensitivity, specificity, and accuracy were compared for the three modalities. No significant difference in Az, sensitivity, specificity, or accuracy was obtained among gadoxetic acid-enhanced MRI, MDCT, and angiography-assisted CT for both readers. For reader 1, the sensitivity (55.6%) and the accuracy (84.7%) of angiography-assisted CT were significantly higher than those of MDCT (33.3% and 78.0%) (P < 0.05). Gadoxetic acid-enhanced MRI has a relatively high diagnostic ability to detect HCC even in recipients of LRLT, equivalent to the abilities of MDCT and angiography-assisted CT.

Covered Self-Expandable Metal Stents for the Treatment of Benign Biliary Strictures After Liver Transplantation: When and How?

Benign biliary strictures (BBS) may complicate biliary surgery including liver transplantation (LT) [1]. The firstline management of BBS, including anastomotic strictures after LT, now incorporates endoscopic therapy, mostly consisting of stenting [2]. Although originally designed for endoscopic palliation of malignant biliary strictures, the self-expandable metallic stent (SEMS) is a valid alternative to surgery for BBS. Patients with malignant biliary strictures who undergo treatment with metal stents have a limited life expectancy due to the poor prognosis of the underlying disease. Therefore, for patients with BBS who have a normal life expectancy, the indications for metal stent placement should differ from those applied to malignant biliary strictures. Metal stents can be divided into uncovered SEMS, partially covered SEMS, and fully covered SEMS (FCSEMS). Non-removable uncovered SEMS cannot be used for BBS due to their limited patency, since reactive hyperplastic tissue may extend through the metal mesh. Partially covered SEMS can be used for BBS to decrease the rate of stent migration; however, the uncovered portion can embed in the bile duct wall. FCSEMS are a good first choice because of their easy removal and long duration of patency due to lack of tissue hyperplasia and implantation into the biliary tree. Since frequent spontaneous stent migration is a major adverse event associated with FCSEMS, an anchoring system such as flared ends or anchoring fins has been developed [3]. In this issue of Digestive Diseases and Sciences, Kahaleh’s group reports the retrospectively analyzed outcomes of covered SEMS for 55 patients with anastomotic strictures after LT [4]. Twenty-seven of 55 (49.1 %) patients were treated with plastic stents prior to covered SEMS. The authors applied three different types of covered SEMS: partially covered SEMS (19 patients), FCSEMS with anchoring fins (21 patients), and FCSEMS with flared ends (15 patients). Endoscopic biliary sphincterotomy was performed in all patients. Although the authors endeavored to center the stent within the stricture, success was not universal. All covered SEMS were removed after 3–4 months. The technical success rate was 100 %, but the clinical success rate, as measured by stricture resolution, was unsatisfactory (60–74 %). Even after covered SEMS placement, three (5.5 %) patients eventually required surgery to resolve their biliary strictures. Notably, the stentrelated adverse event rate involving migration and occlusion was 7–24 %. Five patients with early stent occlusion required repeat stenting. Indeed, the clinical success rate of endoscopic stenting with multiple plastic stents is reportedly 87–94 % [5]. The location of the stricture is usually the most proximal aspect of the common hepatic duct in anastomotic strictures after LT, especially after living-related LT recipients, in whom the strictured segment is usually short. To achieve effective stenting with covered SEMS, the stent should be centered within the strictured bile duct segment, which might be difficult to achieve in this clinical setting. Stenting with conventional covered SEMS distal to the stricture of the recipient’s native common bile duct can abruptly stretch the duct due to the high radial force developed J. H. Moon Department of Internal Medicine, Digestive Disease Center and Research Institute, Soonchunhyang University School of Medicine, Bucheon/Seoul, Korea

Multidetector CT in pre- and post-operative evaluation of living-related liver transplantation

ObjectiveTo assess the role of multi-detector CT (MDCT) in the pre and post operative evaluation of both potential donors and recipients for living related liver transplantation (LRLT). Material and MethodsThis prospective study included 26 patients for LRLT and their corresponding donors. For preoperative assessment, all subjects were evaluated by triphasic CT abdomen. CT angiography (CTA) with 3D reconstruction and CT volumetry was additionally done for donors. CT findings were compared to surgical results as gold standard reference. In post-operative evaluation, CT abdomen was performed at least once after transplantation for all recipients and for indicated donors. CTA was done for indicated recipients when US findings were inconclusive. ResultsNo statistically significant difference was found between CT volumetry and intraoperative findings. Compared to surgical findings, MDCT identified hepatic arterial and portal venous anatomy with 100% sensitivity and specificity, while for hepatic venous anatomy; it showed sensitivity and specificity of 85.7% and 84.2%. Biliary complications and fluid collections were the commonest in recipients and donors respectively. ConclusionMDCT is a single comprehensive non-invasive and accurate imaging modality for preoperative evaluation of liver parenchyma, hepatic vascular anatomy and graft volume and postoperative complications in donors and recipients of LRLT.

Effects of Cholestasis on Whole Blood Concentration of Tacrolimus, an Immunosuppressant, in Living-Related Liver Transplant Recipients

Background: To explore the effects of cholestasis on whole blood concentration of tacrolimus (TAC), an immunosup-pressant, we investigated the relationship among blood TAC concentration, bile flow, and TAC metabolites in bile, as well as the relationship between total bilirubin (T-Bil), an index of cholestasis, and blood TAC concentration, in liver transplant recipients. Methods: Data were collected retrospectively from 16 male and 19 female patients (mean age: 38 years; range: 12 -59 years) who had undergone a living-related liver transplantation at Kyoto Prefectural University of Medicine from 2004 through 2008. Analysis of TAC, demethyl-TAC, and hydroxy-TAC in bile was performed by LC-MS/MS. Results: There was no correlation between the ratio of TAC metabolite to TAC in bile (M/P) of demethyl-TAC and post operation days (POD), whereas a weak linear correlation was demonstrated between M/P of hydroxy-TAC and POD (r = －0.345). Moreover, linear correlations were not observed between M/P and the TAC trough level normalized dose (TLTAC/dose), and between TLTAC/dose and POD. A negative linear correlation was demonstrated between bile flow and T-Bil in blood (r = －0.495). Furthermore, a positive linear correlation was observed between TLTAC/dose and T-Bil (r = 0.598), whereas there was no correlation between bile flow and TLTAC/dose. Conclusions: Improvement of hepatic function and the increase of TAC clearance after postoperative day 7 did not significantly contribute to hepatic TAC metabolism, bile excretion, and TLTAC/dose. Postoperative biliary stricture from liver transplantation with/without biliary drainage caused inter-and intra-patient variability in TLTAC/dose after liver transplantation, which could be assessed by T-Bil. T-Bil in blood might be a predictive biomarker for determining the degree of bile duct stricture and TAC dose in liver transplantation patients. Along with an appropriate dosing regimen, therapeutic drug monitoring including T-Bil would be beneficial and enable individual adjustment of TAC dose in liver transplantation patients.

Performance of radiological methods in diagnosing hepatocellular carcinoma preoperatively in a recipient of living related liver transplantation: comparison with step section histopathology

The aim of the present study was to evaluate the performance of multidetector-row CT (MDCT) and magnetic resonance imaging (MRI) in diagnosing hepatocellular carcinoma (HCC) preoperatively in living related liver transplantation (LRLT) recipients with liver cirrhosis and HCC. A total of 25 LRLT recipients with 89 pathologically proved HCCs underwent dynamic 4-row MDCT (5 mm collimation) and MRI within 1 month before LRLT. The images were reviewed for the diagnosis of HCC on a tumor-by-tumor basis by three observers independently and randomly using explanted specimens as the gold standard. The diagnostic accuracy of these techniques in the detection of HCC was assessed with alternative free response receiver operating characteristic (ROC) analysis. The sensitivity and positive predictive values were evaluated. The average values of the area under the ROC curve (Az) of MRI images were higher than those obtained with MDCT; however, no significant difference was observed (P > 0.05). The overall sensitivity of HCC with MRI was higher than that with MDCT, especially in the case of HCCs <20 mm. A better diagnostic performance regarding HCCs in LRLT recipients was achieved with MRI than with MDCT, although no significant difference was observed.

Oxidative stress after living related liver transplantation subsides with time in pediatric patients

Oxidative stress has been suspected to influence graft survival and prognosis in pediatric recipients of living related liver transplantation (LRLT). We determined the oxidative status of pediatric LRLT recipients during their regular outpatient follow-up visits, and looked for a relationship between oxidative status and post-liver transplantation (post-LTx) duration. The study included 43 patients (20 males and 23 females) between the ages of 1.6 and 25.1 years (median 10.7 years) who had undergone LRLT from 5 months to 17.5 years (median 7 years) prior to the study, between the ages of 1.2 and 14.4 years (median 3.5 years). Serum glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), gamma-glutamyl transpeptidase (γ-GTP), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), direct bilirubin and choline-esterase were measured as part of the patients' regular follow-up visits. Serum total hydroperoxide (TH) and biological antioxidative potential (BAP) were measured using the free radical analytic system which requires 20 μl of serum and 10 min of processing time for each sample. Oxidative stress index (OSI) was calculated as the ratio of TH to BAP. Serum OSI correlated positively with serum levels of GOT, GPT, LDH, ALP, γ-GTP and direct bilirubin. Serum OSI, TH, LDH, ALP and GOT correlated negatively with post-LTx duration. Serum BAP correlated positively with post-LTx duration. Serum TH correlated positively with serum GOT and γ-GTP, but negatively with serum BAP. (1) The OSI, which can be calculated based on data acquired through a simple outpatient procedure, can serve as an index of our patients' laboratory results and oxidative status. (2) The LRLT recipients in our study were at risk for oxidative stress early in the post-operative period, but this risk subsided with time.

Pregnancy after living-related liver transplantation associated with severe preeclampsia and a review of the literature

Pregnancies after orthotropic liver transplantation (OLT) have demonstrated favorable perinatal outcomes. However, obstetrical complications in OLT recipients are more common than those in a normal population. In countries where the number of cadaveric donors is limited, living-related liver transplantation (LRLT) is a valuable procedure, but few pregnancies after LRLT have been reported. We present a case of a pregnant woman after LRLT who developed severe preeclampsia with fetal growth restriction (FGR), and a review of literature. A 34-year-old nulliparous woman was referred to our hospital as a LRLT recipient. She was admitted to our hospital at 25 weeks' gestational age as she had developed severe preeclampsia, although her liver function was stable and there were no episodes for rejection or cholestasis. Emergency cesarean section was performed at 28 weeks' gestational age because of FGR and non-reassuring fetal status. Although there is no Medline available report in English of a successful pregnancy after LRLT, there are 11 cases of successful pregnancies after LRLT in the Japanese literature. These cases suggested that the incidences of preeclampsia, FGR, preterm delivery and cesarean delivery in pregnancies after LRLT are similar to those after OLT, but liver dysfunction and/or cholestasis in pregnancies after LRTL might be more common compared with those after OLT. Careful observation is needed after LRLT and the potential for differences in risk with LRLT recipients in comparison to OLT recipients should be considered.

Early graft dysfunction following adult-to-adult living-related liver transplantation: Predictive factors and outcomes

To describe a condition that we define as early graft dysfunction (EGD) which can be identified preoperatively. Small-for-size graft dysfunction following living-related liver transplantation (LRLT) is characterized by EGD when the graft-to-recipient body weight ratio (GRBWR) is below 0.8%. However, patients transplanted with GRBWR above 0.8% can develop dysfunction of the graft. In 73 recipients of LRLT (GRBWR > 0.8%), we identified 10 patients who developed EGD. The main measures of outcomes analyzed were overall mortality, number of re-transplants and length of stay in days (LOS). Furthermore we analyzed other clinical pre-transplant variables, intra-operative parameters and post transplant data. A trend in favor of the non-EGD group (3-mo actuarial survival 98% vs 88%, P = 0.09; 3-mo graft mortality 4.7% vs 20%, P = 0.07) was observed as well as shorter LOS (13 d vs 41.5 d; P = 0.001) and smaller requirement of peri-operative Units of Plasma (4 vs 14; P = 0.036). Univariate analysis of pre-transplant variables identified platelet count, serum bilirubin, INR and Meld-Na score as predictors of EGD. In the multivariate analysis transplant Meld-Na score (P = 0.025, OR: 1.175) and pre-transplant platelet count (P = 0.043, OR: 0.956) were independently associated with EGD. EGD can be identified preoperatively and is associated with increased morbidity after LRLT. A prompt recognition of EGD can trigger a timely treatment.

Marked Differences in Acute Cellular Rejection Rates between Living-Donor and Deceased-Donor Liver Transplant Recipients

: Due to ongoing organ donor shortage, an increasing number of adult live-donor liver transplants (LDLT) are being performed. The aims of this study were to compare the incidence of ACR between recipients of live- and deceased-donor liver transplants, and to note any differences in ACR among related and unrelated living-donor recipients. : Sixty-four adults undergoing LDLT between 1998-2001 were closely matched with a deceased recipient. Statistical comparisons in ACR between the live- and deceased-donor groups were based on the differences between the ACR rates of each LDLT patient and the corresponding matched deceased recipient. Analyses were performed separately for pairs in which the living donor was not related to the recipient, was a nonsibling relative, or was a sibling. : Live- and deceased-donor recipients underwent a similar number of liver biopsies. In all, 16/50 (32%) of the biopsied LDLT patients had ACR compared to 36/49 (73%) of the deceased-donor recipients. ACR rates of living donors and their deceased-donor matches did not differ significantly for the unrelated living donors, but did differ for the nonsibling related (P=0.03) and the sibling LDLT (P=0.03). The results were similar when comparing rates of high-degree ACR for unrelated, nonsibling related, and sibling pairs. High-degree ACR differences in the sibling LDLT group were significantly greater than in the nonsibling group (P=0.05). : Rates of ACR and high-degree ACR are decreased in living-related liver transplant recipients. This difference is likely genetically related as ACR rates are lower in recipient-donor pairs of increasing genetic similarity.

Elevated blood concentrations of calcineurin inhibitors during diarrheal episode in pediatric liver transplant recipients: Involvement of the suppression of intestinal cytochrome P450 3A and P‐glycoprotein

We encountered two cases of pediatric living-related liver transplant recipients who showed increases in blood concentration of cyclosporine or tacrolimus, a dual substrate for cytochrome P450 (CYP) 3A and P-glycoprotein (P-gp), during a diarrheal episode. To investigate the effect of intestinal inflammation on the metabolic and efflux pump activities, we conducted the experiments using the lipopolysaccharide (LPS)-induced intestinal damage model. Intestinal epithelial CYP3A activity was assessed by nifedipine oxidation using intestinal epithelial microsomes in rat. Drug efflux by P-gp was tested using digoxin flux with the excised intestine perfusion system in rats. Intraperitoneal injection of LPS (0.3 mg/kg) significantly reduced the intestinal epithelial CYP3A activity by 41% (p < 0.01). In the proximal jejunal segment of the rats treated with LPS, mucosal to serosal flux of digoxin was significantly enhanced compared to that of control (p < 0.05). Efflux of digoxin, which was taken up by intestinal epithelium, to mucosal perfusate was significantly blunted in the jejunum treated with LPS (p < 0.05), which indicates that the LPS treatment reduced the P-gp activity in rat small intestine. These findings suggest that the suppression of CYP3A and P-gp activities may be involved in the mechanism of elevated blood concentrations of cyclosporine and tacrolimus during enteritis-induced diarrhea. To prevent a drug-induced adverse effect, dose of a drug, which is a substrate of CYP3A or P-gp, should be reduced during such an episode.

Criteria for immediate postoperative extubation in adult recipients following living-related liver transplantation with total intravenous anesthesia

Study objective To evaluate whether our criteria for immediate postoperative extubation predicts successful extubation in living-related liver transplantation of the right lobe, and to test the effects of our standardized anesthetic technique on the success of immediate postoperative extubation. Design Open-label, descriptive study. Setting University hospital. Patients 6 ASA physical status III and IV patients with end-stage liver disease undergoing living-related liver transplantation of the right lobe. Interventions Patients received a standardized anesthetic technique with propofol, remifentanil, and cisatracurium. They were extubated when they met our criteria for immediate postoperative extubation: good donor liver function, <10 U packed red blood cells administered, hemodynamic stability, and alveolar–arterial oxygen gradient <200 mmHg. Measurements and main results At the end of surgery, four of the six patients fulfilled our criteria for immediate postoperative extubation. They were uneventfully extubated rapidly after surgery and soon arrived in the intensive care unit. Their postoperative stay in the operating room was only 36 minutes (range: 30 to 42 min). No patient required reintubation in the operating room or the intensive care unit. They had no recorded hemodynamic or respiratory problems postoperatively. Conclusions Immediate extubation of selected living-related liver transplant recipients can be a safe procedure. Anesthetic management to immediate extubation seems appropriate and the derived guidelines appear acceptable.

Immediate tracheal extubation of pediatric liver transplant recipients in the operating room.

Keeping patients on mechanical ventilation after orthotopic liver transplantation (OLT) has been a standard anesthetic approach since the first utilization of liver transplantation. Advances in anesthetic management, surgical techniques and patient preparation, in addition to improved postoperative care and the reported advantages of early postoperative tracheal extubation of liver recipients. encouraged us to extubate most recipients at the end of the operation. The aim of the present study is to evaluate the pediatric liver recipients who were extubated immediately at the end of transplantation, in terms of respiratory complications and allograft function during their stay in the ICU. We retrospectively reviewed the records of 40 pediatric recipients who had undergone OLT at the Ege University Organ Transplantation Center between December 1997 and July 2002. Twelve out of 40 patients who had consecutively undergone OLT were extubated immediately at the end of the operation and were included this study. Mean Child Pugh scores of the patients were 9 +/- 2.3 (range 6-12) and the mean PELD score was 23.1 +/- 12.3 (range 7-41). The mean age of the patients was 8.4 +/- 5.2 (range 0.8-16.8 yr). Five of the 12 extubated patients received a cadaveric and seven a living donor liver graft. The mean ICU stay of the patients was 49.1 +/- 24.2 h (6-120 h). No patients required reintubation or mechanical ventilation in the ICU. Respiratory complications diagnosed in the 12 extubated patients were hypercapnia without hypoxemia in three, atelectasis in one and pleural effusion in two. No primary non-function or delayed graft function was detected. The aspartate transaminase (AST), alanine transaminase (ALT) and protrombin time (PT) were normalized within a week. We believe that immediate tracheal extubation in the operating room is a safe procedure for selected cadaveric and living-related liver transplant recipients and will facilitate the patients' recovery and mobilization leading to reduction in complications and a reduced ICU stay.

A role of Helicobacter pylori infection in the development of duodenal ulcer after adult living-related liver transplantation.

Gastrointestinal bleeding caused by peptic ulcer disease is one of the serious complications of living-related liver transplantation (LRLT). The aim of this study was to clarify the factors involved in peptic ulcer formation in adult LRLT recipients. Forty consecutive adult LRLT recipients without a history of peptic ulcer disease were studied. Twenty-five patients (62.5%) tested positive for Helicobacter pylori. After LRLT, duodenal ulcer (DU) developed in six patients, and all of them tested positive for H. pylori. In contrast, none of the H. pylori-negative patients developed DU. Preoperative serum gastrin levels in patients with DU were significantly higher than in those without DU, irrespective of H. pylori infection. Preoperative pepsinogen I levels in patients with DU were significantly higher than in those without DU with H. pylori infection. These data suggest involvement of H. pylori infection in the development of DU after LRLT. Eradication of H. pylori may prevent the development of DU after LRLT particularly in patients with hypergastrinemia and high serum pepsinogen I.

Biliary bacteria in living related liver transplant recipients: microbiology and rapid detection system using flow cytometry.

Since cholangitis is a major complication in living related liver transplant (LRLT) recipients, rapid detection of biliary bacteria is necessary for the management of patients. We have developed a screening method for the detection of biliary bacteria using flow cytometry (FCM). Two hundred and seventy eight bile samples were obtained from 50 patients with biliary drainage tubes after LRLT at Kyoto University Hospital between July and September 2001. Of the 278 samples, 165 (59.3%) were culture-positive. The most common isolates were Enterococcus species, Pseudomonas species, Staphylococcus species, Klebsiella species, and Candida species. As the original FCM system was inadequate for specifically detecting bacteria in bile samples, we established the most appropriate gate and cut-off value from the particle distribution represented on scattergram of the forward-scattered light and fluorescent light intensity. The 3% cut-off value was most preferably related to the culture results. The FCM system detected biliary bacteria with a sensitivity of 93.9%, specificity of 81.4%, positive predictive value of 88.1%, negative predictive value of 90.2%, false-positive rate of 7.6%, false-negative rate of 3.6%, and percent agreement of 88.9% between FCM and culture. Therefore, FCM can be a useful method in clinical laboratories for the rapid screening for biliary bacteria in LRLT recipients.

Circulating antibody to hepatitis B core antigen does NOT always reflect the latent hepatitis B virus infection in the liver tissue

Accumulating evidence suggests the presence of latent hepatitis B virus (HBV) infection in the liver of individuals negative for HBV surface antigen (HBsAg) but positive for antibodies to HBV core antigen (anti-HBc) at low titer. It remains unclear, however, whether positive anti-HBc in the serum invariably reflects latent HBV infection. In this study, we examined the presence of HBV genomes in the liver tissue of 33 donors and 30 recipients of living-related liver transplantation with positive for anti-HBc together with time course changes in their anti-HBc titer. None of these anti-HBc-positive healthy donors or recipients was positive for HBV-DNA nor anti-HBc at high titer (200 dilution) in their sera. However, HBV-DNA was detected in the liver tissue of 24 of 33 healthy anti-HBc-positive donors (72.7%) and five of 30 anti-HBc-positive recipients (16.7%). Interestingly, anti-HBc was continuously positive in all healthy donors tested. In contrast, anti-HBc titers in 75% of recipients, who were positive for anti-HBc at the time of liver transplantation, gradually decreased after the operation, and finally became negative after the mean follow up period of 9.0 months (range 1.2–45.1). Notably, HBV-DNA was never detected in the liver of those recipients who were transiently positive for anti-HBc. In conclusion, our findings suggested the possibility that presence of circulating anti-HBc does not always reflect the presence of HBV genomes in the liver tissue of anti-HBc-positive patients.

Allograft rejection in pediatric liver transplantation: Comparison between cadaveric and living related donors

The aim of this study was to determine whether living related liver transplantation has an immunological advantage compared with cadaveric liver transplants in children. The records of 100 pediatric primary liver transplant recipients performed between January 1992 and December 1998 at the University of California, San Francisco Medical Center, were reviewed retrospectively. Ten children who died or required a second graft within the first 14 post-operative days were excluded from this study group. Two children with combined kidney-liver transplants were also excluded. As a result, the study group included 51 children in the cadaveric liver transplantation (CLT) group and 37 children in the living-related liver transplantation (LRLT) group. Until 1995, primary immunosuppression consisted of cyclosporin A, azathioprine and steroids. Since 1995, primary immunosuppression consisted of cyclosporin A, mycophenolate mofetil and steroids. Actuarial graft survival rates at 1, 2 and 5 yrs were 90%, 80.9% and 80.9% in the CLT group vs. 94.6%, 91.6% and 78.5% in the LRLT group, respectively (NS). Rejection was diagnosed in 40 of 51 cadaveric first grafts (78.4%) and 25 of 37 living-related primary grafts (67.6%). Rejection episodes were diagnosed greater than 1 yr post-transplantation in 11 of 51 cadaveric first grafts (21.6%) and none of 37 living-related primary grafts (0%) (p < 0.05). LRLT succeeded in reducing the immunosuppressive therapy compared with CLT at 24 months after transplantation (p < 0.05). The overall incidence of rejection and graft survival rate were comparable in CLT and LRLT; however, rejection episodes in LRLT recipients diagnosed greater than 1 yr post-transplant were significantly fewer than CLT recipients. LRLT have a partial immunological advantage compared with CLT.

Psychiatric Disorders Before and After Living-Related Transplantation

The authors examined psychiatric disorders among two samples of patients who underwent living-related transplant (LRT) for kidney and liver failure. The postoperative prevalence of psychiatric disorders for adult transplant recipients was highest the first 3 months posttransplant. The incidence of psychiatric disorders in the adult recipients with living-related liver transplant (LRLT) was higher (54%, 22 of 41) than that of adult recipients with living-related kidney transplant (LRKT) (28%, 65 of 234). Twelve (80%) of the 15 adult LRLT recipients with adult child-to-parent donors exhibited paradoxical psychiatric syndrome (PPS). Among the 12 affected recipients, guilt-based psychiatric disorders of various types occurred despite successful operative outcome for both donor and recipient. The higher rate of psychiatric disorders among adult LRLT recipients was associated with the occurrence of PPS among recipients of an adult-child allograft. These results signal a new challenge for consultation psychiatrists working with transplant patients.

Peri-operative blood lactate levels in recipients of living-related liver transplantation.

The role of changes in peri-operative blood lactate levels in recipients of living-related liver transplants has not yet been clarified. Forty-three recipients were included in this study. Blood lactate, plasma total bilirubin, aminotransferase, body temperature, and gastric mucosal PCO2 levels were measured at six time points during surgery: just before the initiation of surgery, just after dissection of the hepatic vasculature, at the end of the anhepatic phase, and 30, 60, and 120 min after reperfusion. We calculated the rate of lactate accumulation during the pre-anhepatic and anhepatic phases and the elimination rate during reperfusion (neohepatic phase), and examined the correlation between these results and the clinical findings. The rate of lactate elimination during the neohepatic phase was correlated with the ratio of graft weight to standard liver volume (P<0.0001). There was also a significant correlation between the rate of lactate accumulation during the pre-anhepatic phase and the preoperative total bilirubin levels (P=0.0008). Each pre-anhepatic, anhepatic, and neohepatic phase had a characteristic blood lactate profile. The graft size strongly affected lactate levels during the early neohepatic phase.

Increase in natural killer cell activity following living-related liver transplantation.

We monitored the serial changes of natural killer cell (NK) activity in eight recipients of living-related liver transplantation. The HLA types of all eight patients were haplotypically identical with those of their donors. Tacrolimus and methylprednisolone were used for immunosuppression. The NK activity before transplantation was 24.1 +/- 20.2% which is surprisingly low when compared with the value for normal individuals (67.7 +/- 13.2%, P < 0.01) or a liver dysfunction group (49.4 +/- 21.9%, P < 0.05). Serial changes in NK activity revealed a minimum of 6.1 +/- 3.6% 1 week after transplantation, gradually increasing to 49.2 +/- 12.5% at 2 months after transplantation. These results suggest that the diseased liver might play an important role in the suppression of NK activity.