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Background With an increasing shortage of deceased donors for liver transplantation, living donor liver transplantation (LDLT) poses a valuable alternative. Therefore, it is important to investigate the risks healthy donors face during and after this procedure. We investigated complications and their impact on long-term health-related quality of life (HRQoL) and physical and mental functioning. Methods Thirty-three out of 51 Belgian liver donors who underwent a donor hepatectomy at the Ghent University Hospital from 1/1/2000 – 31/12/2015 consented to participate. Blood samples, a liver ultrasound, a clinical examination by a liver surgeon, and a socio-psychological interview supervised by a transplant psychologist were conducted. Additionally, participants completed a survey that examined the HRQoL (SF-36 and EQ-5D-3L), Depression, anxiety and stress (DASS), and donor experiences. Fischer’s exact, Mann-Whitney-U test, and Kruskal-Wallis tests were used, and statistical analysis was performed with SPSS 27.0. Results Donor complications were recorded in 24.8% without relation to long-term mental QoL and physical symptoms. Type of lobe donation had no significant effect on HRQoL, mood, anxiety and stress, and complications. Recipient complications and death, negative mood, anxiety, and stress were found to be related to a lower donor physical and mental HRQoL. Patients donating to pediatric recipients scored significantly better for mental and physical HRQoL. Conclusions Generally, donor experience is positive, with own complications having no lasting effect on QoL and mental health, however, complications in the recipient are more difficult to cope with and impact the mental HRQoL of the donor. LDLT in Belgium is ready to be standardized care for end-stage liver disease.

Background HHH syndrome is a rare autosomal recessive disorder of the urea cycle, caused by a deficient mitochondrial ornithine transporter. We report the first successful liver transplantation in HHH syndrome performed in a seven-year-old boy. The patient presented at 4 weeks of age with hyperammonemic coma. The plasma amino acid profile was suggestive of HHH syndrome, and the diagnosis was confirmed when sequencing of the SLC25A15 gene identified two mutations p.R275Q and p.A76D. Although immediate intervention resulted in normalization of plasma ammonia levels within 24 hours, he developed cerebral edema, coma, convulsions, and subsequent neurological sequelae. Metabolic control was difficult requiring severe protein restriction and continued treatment with sodium benzoate and L-arginine. Despite substantial developmental delay, he was referred to our center for liver transplantation because of poor metabolic control. Following cadaveric split liver transplantation, there was complete normalization of his plasma ammonia and plasma amino acid levels under a normal protein-containing diet. This excellent metabolic control was associated with a markedly improved general condition, mood and behavior, and small developmental achievements. Twelve years after liver transplantation, the patient has a stable cognitive impairment without progression of spastic diplegia. Conclusion This first case of liver transplantation in HHH syndrome demonstrates that this procedure is a therapeutic option for HHH patients with difficult metabolic control.

OBJECTIVE: To evaluate the European experience after Adult-to-adult living donor liver transplantation using the left liver (LL-aLDLT). SUMMARY BACKGROUND DATA: LL-aLDLT decreases donor risk but provides a smaller graft that increases recipient risk as compared with right liver (RL-aLDLT). However, there is little knowledge of results obtained after LL-aLDLT in Europe. METHODS: This is a European multicenter retrospective study which aims to analyze donor and recipient outcomes after 46 LL-aLDLT. RESULTS: Seventy-six percent of the grafts were harvested by minimally invasive approach. Mean donor hospital stay was 7.5 ± 3.5 days. Donor liver function was minimally impaired, with 36 donors (78.3%) without any 90-day complication, and 4 (8.7%) presenting major complications. One, 3, and 5-year recipient survival was 90.9%, 82.7%, and 82.7%, respectively. However, graft survival was of 59.4%, 56.9%, and 56.9% at 1, 3, and 5 years respectively, due to a 26.1% urgent liver retransplantation (ReLT) rate, mainly due to SFSS (n = 5) and hepatic artery thrombosis (HAT, n = 5). Risk factor analysis for ReLT and HAT showed an association with a graft to body weight ratio (GBWR) 0.6% was associated with a lower ReLT rate (0% vs. 33%, P = 0.044). CONCLUSIONS: Our analysis showed low donor morbidity and preserved liver function. Recipient outcomes, however, were hampered by a high ReLT rate. A strict selection of both donor and recipients is the key to minimize graft loss.

Background: In patients with hepatocellular carcinoma (HCC), the outcome after liver transplantation (LT) is excellent if tumor characteristics are within the Milan criteria (MC). Expanded Asan criteria (AC) have not yet been validated in Western countries. Methods: A total of 76 patients with HCC underwent LT. Patients were divided and compared according to Milan, UCSF, and Asan criteria. Differences between pre- and post-operative assessment were evaluated. Overall survival (OS) and disease-free survival (DFS) were compared between groups. Predictors of recurrence were investigated. Results: Asan criteria provided 26% and 15% more criteria-fitting patients than MC and UCSF pre-operatively while 49% and 35% at pathological evaluation. Discrepancy between pre- and post-operative evaluation was 32% for MC, 33% for UCSF, and 18% for AC (p=0.06). After a median follow-up of 70.5months, patients exceeding MC but fulfilling Asan had comparable 5-yr OS and DFS to patients fulfilling MC (p=0.17; p=0.29). Patients exceeding UCSF but fulfilling AC had comparable 5-yr OS and DFS to patients fulfilling UCSF (p=0.26; p=0.32). Number of nodules, macro-vascular invasion, capsular invasion, and exceeding AC predicted recurrence at multivariate analysis (p=0.01, 0.03, 0.01, 0.02, respectively). Conclusions: The extension to AC allows increasing the number of patients eligible for LT without affecting OS and DFS.

The portal vein flow (PVF), portal vein pressure (PVP), and hepatic venous pressure gradient (HVPG) were prospectively assessed to explore their relationships and to better define hyperflow and portal hypertension (PHT) during liver transplantation (LT). Eighty-one LT procedures were analyzed. No correlation between PVF and PVP was observed. Increases in the central venous pressure (CVP) were transmitted to the PVP (58%, range = 25%-91%, P = 0.001). Severe PHT (HVPG ≥ 15 mm Hg) showed a significant reciprocal association with high PVF (P = 0.023) and lower graft survival (P = 0.04). According to this initial experience, an HVPG value ≥ 15 mm Hg is a promising tool for the evaluation of hemodynamic stress potentially influencing outcomes. An algorithm for graft inflow modulation based on flows, gradients, and systemic hemodynamics is provided. In conclusion, the evaluation of PHT severity with PVP could be delusive because of the influence of CVP. PVF and PVP do not correlate and should not be used individually to assess hyperflow and PHT during LT.

Haptoglobin (Hp) is a polymorphic plasma protein with multiple functions defined by three major phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2). In this article, the effects of the donor Hp phenotype (determined by starch gel electrophoresis) on the outcome and the iron status after liver transplantation were investigated. A total of 450 liver transplant patients were enrolled in this study with a median follow-up of 37 months. Kaplan-Meier and Cox regression survival analyses showed a significantly worse graft survival for liver transplantation cases with an Hp 2-2 donor phenotype, which was associated with an increased mortality rate in this group. In male patients, the Hp 2-2 phenotype was associated with higher serum ferritin concentrations, which may be linked to the significantly increased likelihood of infectious complications in this phenotype. Liver transplant patients with Hp 1-1 and Hp 2-1 grafts had a better outcome probability than recipients of an Hp 2-2 graft, which may be explained by differences in iron metabolism induced by the Hp genotype of the graft.

Background: The aim of this trial was to confirm previous results demonstrating the efficacy and safety of a fixed combination tissue sealant versus argon beam coagulation (ABC) treatment in liver resection. Methods: This trial was designed as an international, multicenter, randomized, controlled surgical trial with 2 parallel groups. Patients were eligible for intra-operative randomization after elective resection of ≥1 liver segment and primary hemostasis. The primary end point was the time to hemostasis after starting the randomized intervention to obtain secondaty hemostasis. Secondary end points were drainage duration, volume, and content. Adverse events were collected to evaluate the safety of treatments. The trial was registered internationally (Eudract number 2008-006407-23). Results: Among 119 patients (60 TachoSil and 59 ABC) randomized in 10 tertiary care centers in Europe, the mean time to hemostasis was less when TachoSil was used (3.6 minutes) compared with ABC (5.0 minutes; P = .0018). The estimated ratio of mean time to hemostasis for TachoSil/ABC ws 0.61 (95% confidence interval, 0.47-0.80; P = .0003). Postoperative drainage volume, drainage fluid, and drainage duration did not differ between the 2 groups. Mortality (2 vs. 4 patients) and adverse reactions (24 vs. 28 patients) for TachoSil versus ABC did not differ. Conclusion: This trial confirmed that TachoSil achieved significantly faster hemostasis after liver resection compared with ABC. Postoperative morbidity and mortality remained unchanged between both groups.

mesh techniques are the preferable methods for repair of small ventral hernias, as a primary suture repair shows high recurrence rates. The aim of this prospective study was to compare the retromuscular sublay technique with the intraperitoneal underlay technique for primary umbilical hernias.from February 2004 to April 2007, all patients treated for umbilical hernias with maximum diameters of 3 cm were prospectively followed. During the first period of 15 months, all patients were treated with retromuscular repair using a large pore mesh (Vypro). After that period, for all patients, mesh repair using an intraperitoneal Ventralex patch was performed. All patients underwent general anesthesia. This analysis included 116 patients, of whom 56 had retromuscular repair (group I; mean age, 54.8 years; mean body mass index, 28.2 kg/m(2)) and 60 had open intraperitoneal repair (group II; mean age, 48.1 years; mean body mass index, 29.4 kg/m(2)). Operating time was evaluated as skin-to-skin time, and drain management was noted for both techniques. Follow-up was ≥ 2 years for all patients, and both early and late complications were registered, including seroma and hematoma formation, wound infection, fistula formation, and recurrence rates. Preoperative and postoperative pain was evaluated using a visual analogue scale (range, 0-10) on the day of the first outpatient visit; on postoperative days 1, 7, and 21; and after 1 year. Quality of life was estimated using the EQ-5D questionnaire 1 year after surgery. All data were analyzed using SPSS version 15 software. Wilcoxon's rank-sum test was used to analyze continuous variables, and repeated-measures analysis of variance was used for visual analogue scale scores. The χ(2) test and Fisher's exact test were used to assess the differences between categorical data. P values.05 were considered statistically significant.the mean operative times were 79.9 minutes in group I and 33.9 minutes in group II (P.001). The mean hospital stay was significantly longer in group I (3.8 vs 2.1 days, P.001). Seromas and superficial wound infections in the early postoperative period were not different between both groups, although seromas occurred more frequent in the retromuscular group. Postoperative visual analogue scale scores were significantly lower with the intraperitoneal technique at all time points (P.003, repeated-measures analysis of variance). However, 3 patients with the Ventralex patch had to be readmitted for severe pain. The recurrence rate was higher with the intraperitoneal repair (n = 5 [8.3%] vs n = 2 [3.6%]) than for the retromuscular mesh repair, but not statistically significant. Quality of life was comparable in the two groups after 1 year.the open intraperitoneal technique using a Ventralex mesh for umbilical hernias seems a very elegant and quick technique. However, possibly because of the less controllable mesh deployment, recurrence rates seem higher. In case open mesh repair is the preferred treatment, a retromuscular repair should be the first choice.

Background Decreasing the amount of polypropylene by increasing pore size produces a lighter weight mesh that may improve tissue ingrowth and, functional properties of the abdominal wall and diminish mesh-related complications. It was the aim of this prospective observational cohort study to analyze the outcome of incisional hernia repair using small-pore versus large-pore meshes and using a standardized, open, retromuscular surgical technique. Methods Across a 6-year period we analyzed 205 patients treated with a heavyweight mesh (group I) and 235 patients treated with a large-pore mesh (group II) for incisional hernias. Patients with a body mass index greater than 40 kg/m2 and patients with hernias with a transverse diameter of more than 10 cm were not treated by a retromuscular mesh repair and are not included in this analysis. Recurrent incisional hernias also were not included. Both groups had 3 years of follow-up. Patients were evaluated for pain, discomfort, feeling of foreign material, and recurrences. Results Pre-operative characteristics were comparable between the groups, including body mass index, diabetes, and smoking. The mean total hernia surface was 56 cm2 for group I versus 48 cm2 in group II. The mesh surface area was 448 cm2 for group I and 425 cm2 for group II. Considering pain scores, there was only a minor difference between the 2 groups at 1-month follow-up, at which time, the Visual Analogue Scale was 5.8 in group I and 4.9 in group II (P = .16). All other scores were comparable between the groups. In group I, 7 recurrences (3.4%) were recorded after 3 years, of which 6 were already apparent 1 year after initial repair. In group II, 9 recurrences (3.8%) were diagnosed, again 6 within the first year after repair. Conclusion Large-pore meshes can be used safely for open primary incisional hernia repair with an equal outcome compared with small-pore meshes in nonobese patients with defects smaller than 10 cm in width, in regard to both recurrence rates and chronic discomfort.

PURPOSE: The aim of this study was to compare the transinguinal preperitoneal technique (TIPP) using a memory ring patch versus the Lichtenstein technique in relation to acute and chronic pain, post-operative complications and recurrence rates.METHODS: During an 18-month period, all adult patients that needed treatment for a unilateral inguinal or femoral hernia were treated by the TIPP repair using the Polysoft mesh. This group was retrospectively compared with a historical cohort of patients treated by the Lichtenstein technique. Our policy concerning type of anaesthesia, post-operative pain management and visual analogue scale measurements did not change over the study period. For post-operative pain evaluation, the visual analogue scale was used (0-10) and scores were measured after 6 h, 24 h, 1 week, 1 month, 1 year and yearly thereafter. Recurrence rates were evaluated at time of clinical examinations.RESULTS: In total, 142 patients have been analysed with the TIPP technique (group I) versus 136 patients operated in the previous 2 years with a Lichtenstein repair (group II). In group I, 112 patients (78.9%) received a medium size patch of 14 x 7.5 cm and 30 patients (21.1%) had a large patch (16 x 9 cm). The mean operative time for a TIPP procedure was statistically shorter than for a Lichtenstein repair, 33 versus 44 min, respectively (p = 0.04). After 24 h, 1 week and 1 month post-surgery, there was significantly less post-operative pain observed in the TIPP group than in the Lichtenstein group. In total, four recurrences were observed in the TIPP group (2.8%), of which one laterally and three medially. In group II, seven recurrences were observed in total (5.1%), of which five were detected within 2 years of follow-up (3.7%).CONCLUSION: For surgeons performing the Lichtenstein repair but looking for modifications concerning pain relief and a quicker procedure, the TIPP approach is a feasible alternative that seems to be associated with less post-operative pain.

The Belgian experience with donation after cardiac death (DCD) liver transplantation (LT) was retrospectively reviewed, particularly evaluating patient and graft survivals, and biliary complications. From 2003 to 2007, 58 DCD-LT were performed in Belgium. Mean procurement total warm ischemia time was 25 +/- 2 min (mean +/- SEM). Mean cold ischemia time was 451 +/- 18 min. Mean follow-up was 23 +/- 2.2 months. Post-transplant peak aspartate aminotransminases was 2241 +/- 338 UI/l. Patient survivals at 1 month, 1 and 3 years, were 91.3%, 83.3% and 66.9% respectively. Graft survivals at 1 month, 1 and 3 years, were 84.4%, 72.4% and 48.8% respectively. Two patients (3.4%) developed primary nonfunction. Regarding the biliary complications, seven grafts (12%) were lost because of intrahepatic cholangiopathy, and 12 other patients (20.6%) developed bile duct stenoses requiring endoscopic and/or surgical management. The rate of symptomatic ischemic biliary lesions for grafts surviving more than 3 months was 38% (19/50). Although DCD organ donors may be a source of viable liver grafts, results were inferior to those obtained with donation after brain death LT in this series. Prognostic criteria have to be developed to improve results of DCD-LT.

We designed a pilot trial in cadaveric liver transplantation to determine whether induction with antithymocyte globulins (ATG) and sirolimus would allow immunosuppression withdrawal. Patients received ATG 3.75 mg/kg per day from day 1 to 5 after transplantation followed by sirolimus for 4 to 6 months. We monitored interleukin (IL)-7 serum levels, interferon (IFN)-gamma, and IL-2 mRNA accumulation in mixed leukocyte reaction and intragraft IFN-gamma mRNA expression. In the first three patients, immunosuppression discontinuation was followed by reversible acute rejection occurring on days 280, 246, and 163 posttransplantation, corresponding to days 140, 40, and 39 after drug withdrawal, respectively. At the time of rejection, blood CD8+ T-cells counts had returned to or above pretransplant levels in two of three patients, whereas CD4+ T-cell count remained low. IL-7 serum levels rose in all three patients in the first months after transplantation and IFN-gamma mRNA accumulated in mixed leukocyte reaction between recipient T cells and donor spleen cells at the time of rejection. High levels of IFN-gamma mRNA were consistently detected in liver biopsy performed at the time of rejection. In conclusion, lymphopenia-induced IL-7 production after induction with ATG and sirolimus might lead to emergence of IFN-gamma-secreting CD8+ T-cells responsible for acute rejection after immunosuppression withdrawal.

Increased expression of glucose transporters has been reported in many cancers. It is not known whether Sodium dependent GLucose Transporter 1 (SGLT1) is up-regulated in pancreatic cancer. We studied the expression of SGLT1, Bcl-2 and p53 in primary pancreatic adenocarcinomas related to survival. In primary tumors, mean SGLT1-Hscore (n = 83) was 4.24 (median 3.0, range 0.5-15.0). Patients with positive staining for Bcl-2 had higher mean SGLT1-Hscores than those without Bcl-2 expression: 5.87 vs. 3.07 (P = 0.025). No correlation was found between expression of p53 and SGLT1 (P = 0.881). On multivariate analysis TNM stage (P = 0.015) and SGLT1 (P = 0.030) showed prognostic value for disease free survival (DFS). For overall survival (OS), TNM stage (P0.001) and chemotherapy (P = 0.048) were prognostic and SGLT1 showed a trend (P = 0.071). In a subgroup of younger patients (ageor = median, 63.9 y) who did not receive chemotherapy, SGLT1 was a very strong predictor of DFS (P = 0.005). We conclude that high SGLT1 expression (H scoremedian, 3.0) in pancreatic adenocarcinomas was significantly correlated with DFS and a trend was found for OS, especially in younger patients. High SGLT1 expression in primary tumors was correlated with high Bcl-2 expression, not with p53 expression. This supports our hypothesis that SGLT1 and Bcl-2 expression could serve as prognostic markers in pancreatic cancer.

Laparoscopic liver resection (LLR) has gained wide acceptance for various liver resection procedures, mainly for benign diseases. However, only small series have been reported from a few selected centers.Between January 2001 and January 2006, a total of 629 liver resections were performed at our institution. The indication was solid benign liver tumor in 56 (8.9%) patients. LLR was performed in 20 (35.7%) cases. Data from the LLR group were compared with those from a consecutive control group undergoing open liver surgery (OS) for similar indications in a matched-pair analysis during the same period. The pairs were matched as closely as possible for age, gender, American Society of Anesthesiologists (ASA) score, indication for resection, and type and location of the lesions. The endpoint was to investigate overall morbidity and outcome.All patients but one are alive and well after a mean follow-up of 35 months (range 10-60 months). Conversion laparotomy was required in two out of 20 (10%) cases for uncontrolled bleeding (one requiring temporary hemodialysis). LLR was characterized by faster time to first oral intake and shorter hospital stay compared to OS (p = 0.001 and 0.008, respectively). Incisional hernias (25%) were only recorded in the OS (p = 0.047 vs. LLR). Overall morbidity was 45% in OS versus 20% in LLR (p = 0.3).LLR significantly reduced time to oral intake, hospital stay, and incisional hernias compared to OS. Bleeding is a major risk and should be carefully considered when resecting benign tumors. In the hands of expert surgeons, LLR may become the gold standard for the resection of benign liver tumors located in the anterior and lateral sectors and for minor hepatic resections.

Background: Non-invasive staging of human liver fibrosis is a desirable objective that remains under extensive evaluation. Animal model systems are often used for studying human liver disease and screening antifibrotic compounds. The aim of the present study was to investigate the potential use of serum N-glycan profiles to evaluate liver fibrosis in a rat model. Methods: Liver fibrosis and cirrhosis were induced in rats by oral administration of CCl4. Liver injury was assessed biochemically (alanine aminotransferase [ALT] activity, aspartate aminotransferase [AST] activity and total bilirubin) and histologically. The N-glycan profile (GlycoTest) was performed using DNA sequencer-assisted–fluorophore-assisted carbohydrate electrophoresis technology. In parallel, the effect of cotreatment with antifibrotic interferon-γ (IFN-γ) was studied. Results: The biopsy scoring system showed that CCl4 induced early fibrosis (F

Despite all recent developments in surgical techniques during liver surgery, blood loss is still one of the main causes for postoperative morbidity and mortality. Other complications include bile leakage and fluid accumulation intraperitoneally. Fibrin sealants are able not only to enhance clot formation and wound healing but possibly work as a sealing device for postoperative leakage and fistula formation. In this overview the underlying mechanisms for these agents are discussed and several clinical data concerning liver surgery will be reported.

New immunosuppressive agents and regimens should be evaluated specifically in living donor liver transplant patients due to potential clinical and pharmacokinetic differences between deceased donor and living donor transplant recipients. The analysis presented here is the first direct comparison of clinical outcomes using cyclosporine microemulsion (CsA-ME) with monitoring of blood concentration at 2 hours postdose (C2) and tacrolimus-based immunosuppression in living donor liver transplantation. The analysis was conducted on the data provided by the 39 recipients of a living donor transplant out of the 495 patients enrolled in a 6-month, randomized, prospective, multicenter, open-label study (LIS2T). Patients were randomized to CsA-ME (C2 monitoring) or tacrolimus (monitoring of predose trough drug blood level [C0)]) and were administered corticosteroids with or without azathioprine. Twenty-three living-donor patients received CsA-ME and 16 received tacrolimus. By month 6, 9% of patients receiving CsA-ME and 19% of those receiving tacrolimus had lost their graft or died ( not significant [NS]). Nine episodes of biopsy-proven acute rejection were reported: 4 in the CsA-ME group (17%) and 5 in the tacrolimus cohort (31%, NS). There were no significant differences in any safety parameter between groups. The most frequently reported serious adverse events were infections, which occurred in 14 patients in the CsA-ME group (61%) and 13 patients in the tacrolimus arm (81%, NS). Twelve patients in the CsA-ME arm (52%) and 5 in the tacrolimus arm (31%, NS) discontinued the study prematurely. In conclusion, CsA-ME C2 monitoring or tacrolimus both offer effective protection against rejection in living donor liver transplants while maintaining a good safety profile. (Liver Transpl 2005;11:1395-1402.)

The aim of the present study was to evaluate the influence of low-dose perioperative octreotide on the prevention of complications (pancreatic fistula and general complications) in patients undergoing pancreatic surgery followed by pancreaticojejunostomy. A total of 105 patients were randomized to receive either octreotide 0.1 mg subcutaneously 3 times/day for a total of 7 days or no octreotide. The primary endpoints were the occurrence of a pancreatic fistula and or general complications, including extended length of hospital stay. There were 25 surgical draining procedures performed and 80 duodenopancreatectomies with or without preservation of the pylorus. In all, 25 (23.8%) of the patients were treated for chronic pancreatitis, 8 (7.6%) for benign tumoral disease, and 72 (68.6%) for carcinoma. All patients underwent pancreaticojejunostomy.

Rapid, simple, and reliable assays to monitor allogeneic responses are essential for the safe development of novel protocols of tailored immunosuppression. Herein, we describe a real-time polymerase chain reaction method based on interleukin-2 and interferon-gamma mRNA quantification upon stimulation of whole blood with allogeneic T cell-depleted peripheral blood mononuclear cells. The technique requires only small blood volumes and results can be obtained within 48 hours. Data obtained in a liver transplant patient receiving a tolerance induction protocol based on the infusion of donor-type hematopoietic stem cells suggest that this rapid whole blood mixed lymphocyte reaction assay could be valuable for the monitoring of patients undergoing solid organ or hematopoietic stem cell transplantation.

Aim: The aim of this study was to investigate the effect of octreotide in the perioperative course of pancreas transplants drained into the bowel in terms of fistula formation, pancreatitis, hemorrhage and thrombosis, and to compare the results to patients not receiving octreotide in a prospectively, randomized single center trial. Patients and methods: Forty pancreas transplant recipients were prospectively randomized to either receive or not to receive octreotide 0.1 mg subcutaneously at the time of operation and 3×/d there after until post-operative day 7. The incidence of pancreatic leakage from the anastomosis and the content of peritoneal fluid drainage regarding amylase and lipase concentrations collected by abdominal drains were registered on day 0–10. Both groups were comparable for age, sex, onset of diabetes, surgical procedure and immunosuppressive regimen. Results: There were 35 simultaneous pancreas-kidney transplants and five solitary pancreas transplants, two in the octreotide and three in the control group two pancreas after kidney, one pancreas after liver pancreas, one pancreas after simultaneous pancreas kidney transplantation, one pancreas transplant alone. All had enteric drainage. Twenty patients received octreotide and 20 did not. In one patient, receiving octreotide the pancreas had to be removed for septic complications because of an enteric fistula arising from the anastomosis (1/20 = 5%). The incidence in patients on octreotide vs. non-octreotide was 1 vs. 0 for pancreatitis, 2 vs. 3 for hemorrhage, 2 vs. 1 for thrombosis and 2 vs. 0 for pancreatic fistulae resulting in an actual overall 12 months patient survival of 100% in both groups and a pancreas survival of 85% vs. 95%. For primary simulaneous pancreas kidney the pancreas graft survival was 93%. The amylase and lipase concentrations of fluid collections drained into the peritoneum on day 0 to 10 post-operatively indicating pancreatic fistulization was comparable in both groups. Conclusion: The use of octreotide following pancreas transplantation did not prevent pancreatic fistula formation from the anastomosis neither from the pancreatic capsule in pancreas transplantation with enteric drainage. Further studies are required to finally evaluate the benefit of this prophylactic treatment.

Background and aim of the study: The induction of transplantation tolerance, defined as the survival of a functioning allograft in the absence of continuing immunosuppressive therapy, would be a major advance. Clinical and experimental data have shown that transplantation tolerance could be induced by pre-transplant myeloconditioning and infusion of donor hematopoietic cells. We investigated the feasibility and safety of a protocol to induce tolerance to HLA mismatched living-donor liver graft by pre-transplant non-myeloablative conditioning followed by donor stem cells (SC) infusion, in patients with advanced liver cancers. Patients and methods: Two patients with intrahepatic cancers who did not fulfill criteria for cadaver liver transplantation were included in the study. Preparative regimen consisted in cyclophosphamide and anti-thymocyte globulin, followed by infusion of purified donor CD34+ stem cells. Living-donor liver transplantation (LDLT) using the liver right lobe was performed after hematological reconstitution, respectively 40 and 55 days after donor stem cell infusion. Immunosuppressive therapies were discontinued when liver graft function returned to normal. Results: The procedure could be completed in the two patients. No severe toxicity of the preparative regimen was observed. Neither patient presented graft versus host reaction after donor stem cell infusion. A transient macrochimerism was observed in the first case, while no chimerism could be detected in the second. Immunosuppression was discontinued, respectively 90 and 28 days, after liver transplantation, without subsequent rejection episode. In the two cases, liver function remained normal for the study period. In both patients, the period of immune reconstitution was prolonged, as illustrated by persisting low CD4+ cell counts. Mixed lymphocyte cultures, performed after immunosuppression withdrawal, demonstrated donor specific hyporesponsiveness in the first case, but in a context of global hyporeactivity in the two patients. The first patient died from tumor recurrence 370 days after liver transplantation. The second patient is alive, 270 days after liver transplantation, but with a suspicion of tumor relapse as indicated by the reappearance of tumor marker in blood. Conclusion: In the two cases, acceptance of HLA mismatched living-donor liver graft was obtained after non-myeloablative conditioning and donor stem cell infusion. Improving the rate of immune reconstitution appears as a priority to reduce the risk of tumor recurrence in such patients.

Objective: The HepatAssist liver support system is an extracorporeal porcine hepatocyte-based bioartificial liver (BAL). The safety and efficacy of the BAL were evaluated in a prospective, randomized, controlled, multicenter trial in patients with severe acute liver failure. Summary Background Data: In experimental animals with acute liver failure, we demonstrated beneficial effects of the BAL. Similarly, Phase I trials of the BAL in acute liver failure patients yielded promising results. Methods: A total of 171 patients (86 control and 85 BAL) were enrolled. Patients with fulminant/subfulminant hepatic failure and primary nonfunction following liver transplantation were included. Data were analyzed with and without accounting for the following confounding factors: liver transplantation, time to transplant, disease etiology, disease severity, and treatment site. Results: For the entire patient population, survival at 30 days was 71% for BAL versus 62% for control (P = 0.26). After exclusion of primary nonfunction patients, survival was 73% for BAL versus 59% for control (n = 147; P = 0.12). When survival was analyzed accounting for confounding factors, in the entire patient population, there was no difference between the 2 groups (risk ratio = 0.67; P = 0.13). However, survival in fulminant/subfulminant hepatic failure patients was significantly higher in the BAL compared with the control group (risk ratio = 0.56; P = 0.048). Conclusions: This is the first prospective, randomized, controlled trial of an extracorporeal liver support system, demonstrating safety and improved survival in patients with fulminant/subfulminant hepatic failure.

Following liver transplantation, all hepatic nerves are transected; thus, liver allografts are completely isolated from neural control of their hosts. Despite this absolute denervation, liver allograft function does not appear to be significantly impaired after successful transplantation. In experimental animal models, hepatic denervation has no major effects on bile acid production and biotransformation, while it increases blood pressure and salt retention; decreases the number of hepatic progenitor cells, cholangiocyte proliferation, and liver regeneration; and influences the hepatic microcirculation, diet behavior, and glycemic control. In humans, hepatic denervation after liver transplantation has no major deleterious effects on bile secretion, liver regeneration, and hepatic blood flow. Insulin resistance and postprandial hyperglycemia, changes in ingestion behavior, and reduced stimulation of hepatic progenitor cells in the canals of Hering are the major side effects of absent liver innervation. Despite these abnormalities, patients can lead a new life with improved quality of life.

Background University of Wisconsin (UW) solution (Viaspan) is currently used to preserve organs from nonheartbeating donors. Histidine-tryptophan-ketoglutarate (HTK) solution (Custodiol) is of proven efficacy in experimental pancreas preservation, but its efficacy in combined warm ischemia (WI) and cold ischemia (CI) is unknown. The viability of HTK-preserved porcine pancreatic grafts was assessed after various periods of WI and compared with grafts flushed and preserved with UW solution. Methods A total of 14 pigs were used: G1 (n=4, UW) and G2 (n=4, HTK) with 15-min WI and 16-hr cold storage; G3 (n=3, UW) and G4 (n=3, HTK) with 30-min WI and 16-hr cold storage. Results All animals in G1 and G2 were normoglycemic, whereas only 66% of pancreases were functioning in G3 and G4. HTK perfusion was associated with increased wet weight. Transient hyperinsulinemia was noted in all the groups on postoperative day 1 (mean range: 8.9-12.4 microU/L). Postoperative serum amylase and lipase were more pronounced in G3 and G4. However, HTK-stored grafts exhibited less evidence of biochemical pancreatitis as compared with UW-stored grafts on the first postoperative day in the group with 15-min WI. Mean K values of intravenous glucose tolerance tests on postoperative day 14 were similar in both groups. Vascular congestion was uniformly observed and was considered a typical feature of WI. Conclusions Porcine pancreatic grafts are viable after 16-hr CI following 15-min WI in this experimental nonheartbeating donor model. HTK solution seems to provide reliable graft function in this setting and to be equivalent to UW.

Guillain-Barré syndrome is characterized by acute paralysis and ascending neuropathy due to an inflammatory attack on the myelin of peripheral nerves. About 2/3 of patients with Guillain-Barré syndrome have an infection 1-3 weeks before the onset of the symptoms. Guillain-Barré syndrome has rarely been reported after solid organ transplantation (18 cases with three cases after liver transplantation), and these cases are mostly related to a CMV infection. We describe a 64-year-old male patient who developed Guillain-Barré syndrome related to a Campylobacter fetus enteritis, 70 days post liver transplantation. Although the patient received tacrolimus as immunosuppressant agent and is hepatitis C positive, we can conclude that the Campylobacter infection was probably the primary trigger for the development of Guillain-Barré syndrome. As T-cell response is depressed in our patient and cross-reactive antibodies (anti-ganglioside GM-1) exists after Campylobacter infection, we suppose that a humorally mediated attack is responsible for Guillain-Barré syndrome after solid organ transplantation. A review of the literature is performed.

Although portal venous supply is considered essential to preserve hepatic integrity, in this study, effects of portal arterialization on liver regeneration were evaluated in a rat model of partial hepatectomy (PH). Ninety-six Lewis rats were randomly assigned to four groups of 24 rats each: PH only (group 1), PH with either venous or arterialized portal supply (groups 2 and 3, respectively), and PH without portal supply (group 4). Liver regeneration rate (LRR), 5-bromo-2-deoxyuridine (BrdU) labeling index, and liver biological characteristics were assessed on days 1, 2, 3, and 7. Compared with group 1, all tested rats had a marked body weight loss after surgery, and only rats in group 4 showed no signs of recovery on day 7. With maintained portal inflow (groups 1, 2, and 3), LRRs increased steadily to day-7 values of 89.2% [plusmn] 11.8%, 81.4% [plusmn] 8%, and 77.4% [plusmn] 9.4%, respectively (P = not significant), and 24-hour peak values of BrdU labeling index were 159 [plusmn] 26, 157 [plusmn] 42, and 149 [plusmn] 48, respectively (P = not significant). Conversely, rats deprived of portal supply (group 4) showed profound inhibition of these two parameters (14 [plusmn] 13; P [lt ] .01;32.1% [plusmn] 7.7%; P [lt ] .001, respectively). These results indicate that proper portal blood supply is essential to initiate and maintain liver regeneration after PH. With an equivalent portal inflow rate of either venous or arterial source, the hepatic regeneration response can be sustained. (Liver Transpl 2002;8:146-152.)

The MRI characteristics of a multifocal inflammatory pseudotumor of the liver are described. Emphasis is placed on the appearances following intravenous administration of both non-specific and liver-specific MR contrast agents. On post-gadolinium gradient-echo (GE) images an early, intense, and peripheral enhancement was followed by a homogeneous, complete, and persistent enhancement. Lesions showed no uptake following administration of ferumoxides particles nor mangafodipir trisodium, respectively. During follow-up, a peripheral hyperintense rim appeared on precontrast T1-weighted images, a feature not previously described.

Following a heterotopic auxiliary liver transplantation, commonly used measurements are either invasive or non-indicative of individual viability of the coexisting engrafted and native livers. Magnetic resonance imaging (MRI) was therefore tested for its potential to monitor the post-transplant hepatic viability in a rat model. Thirteen Wistar rats were systematically evaluated with MRI and serum biochemical liver parameters. Post-transplant complications and the causes of animal death were identified by autopsy and histo-pathological examinations. The data of the healthy survivors were compared with those of the rats that developed complications. On MRI, the hepatic complications could be depicted in the individual livers. A specific pattern of signal evolution was found in the livers of the healthy survivors: the mean T1 relaxation times of the engrafted livers increased immediately after transplantation (476 ± 64 ms, mean ± standard deviation, pre-operative; 730 ± 48 ms, week 1) and then declined steadily to a 3 month value of 489 ± 246 ms, while, following a transient first rise (476 ± 64 ms, pre-operative; 589 ± 28 ms, week 1), the mean T1 value of the native livers increased again 4 weeks after surgery and reached a 3 month value of 859 ± 43 ms. However, in the rats with various complications, the mean T1 relaxation times of the engrafted livers continued to increase throughout the first post-operative month (760 ± 48 ms, week 1; 922 ± 76 ms, week 4), while that of the native liver only varied mildly (546 ± 25 ms, week 1; 473 ± 25 ms, week 4). After the first post-transplant week, the healthy engrafted livers could already be distinguished from those with complications by a significant decrease in T1 relaxation times. These data suggest that, besides demonstrating major complications, MRI may allow one to monitor the viability of each liver by analysing the relative signal intensity and T1 relaxation times after a heterotopic auxiliary liver transplantation. Copyright © 2001 John Wiley & Sons, Ltd.

To study the effects of preoperative radiochemotherapy (RCT) on the healing of colonic anastomosis, the rectosigmoid colon in male Wistar rats was irradiated up to an end dose of 41.6 Gy (RT) or sham-irradiated (SR). During the last 5 days of the irradiation schedule, 5-fluorouracil (5-FU) was administered intraperitoneally in either a high dose (20 mg/kg, chemotherapy-high dose [CH]) or a low dose (10 mg/kg, chemotherapy-low dose [CL]). Animals were randomly arranged into six groups: group I, control (SR + saline intraperitoneally); group II, RT only; group III, SR + CL; group IV, RT + CL; group V, SR + CH; group VI, RT + CH. Four days after RCT, a side-to-side anastomosis was constructed between the irradiated rectosigmoid and the nonirradiated caecum. Animals were killed 10 days postoperatively. No significant differences were found in the anastomotic bursting pressure or the bursting wall tension. In group VI, mitoses were less (P < 0.01) and mucosal ulceration was more (P = 0.03) pronounced compared to group I. Sclerotic arteries were seen in all irradiated groups and in animals that received high-dose 5-FU alone. 5-FU administration in high or low dose, with or without RT, induced more inflammation in the submucosa compared to controls (P < 0.05). Conclusively, RCT has no detrimental effect on the mechanical strength of colonic anastomosis in this rat model. However, RCT with high-dose 5-FU induces more histological alterations at the anastomotic site.

Alcoholic liver disease (ALD) is the second most common indication for liver transplantation. The aim of this study was to evaluate the alcohol relapse rate and long-term survival after liver transplantation for ALD and to identify risk factors predisposing to alcohol relapse.Between 2000 and 2007, 108 patients transplanted for ALD in the Ghent University Hospital were included in this retrospective analysis. Relapse was defined as any drinking after transplantation, problem drinking as more than 2 units/day for women and 3 units/day for men. A wide range of variables was obtained from a questionnaire and medical records.The mean follow-up was 55 months. Relapse was observed in 29%, 16% in problem drinking. The one- and five-year survival was 87% and 74% respectively. No significant difference in survival was found between non-relapsers, occasional drinkers and problem drinkers. The following risk factors were found to be significantly associated with relapse into problem drinking in an univariate analysis: a shorter pre-transplant abstinence period, the presence of a first degree relative with alcohol abuse and a higher number of prior attempts to quit. In multivariable analysis, the presence of a first degree relative with alcohol abuse was found associated with relapse into problem drinking.The presence of a first degree relative with alcohol abuse is a valuable pre-transplant variable evaluating an ALD patient's eligibility for liver transplantation. Other variables are also helpful to outline the broader context of the drinking behavior of the patient.

Variant estrogen receptors may be found in hepatocellular carcinoma and may influence its natural history. Because it is not known whether their occurrence is an early or a late event during the course of chronic liver disease or whether they cluster in some subgroups of patients, we investigated a series of patients in different stages of chronic liver disease. One hundred eleven consecutive patients were studied for variant estrogen receptor transcripts by reverse-transcription polymerase chain reaction of RNA extracted from liver biopsy specimens. In chronic active hepatitis, variant estrogen receptor transcripts were coexpressed with wild-type significantly more often in men than in women (P = .029) and in hepatitis B surface antigen (HBsAg)-positive subjects than in subjects positive for antibody to hepatitis C virus (P = .0006). In hepatocellular carcinoma, again in men (P = .004) and in HBsAg-positive patients (P = .0015), the variant estrogen receptor transcript was overexpressed or remained the only one expressed. Patients with liver cell dysplasia presented with the same estrogen receptor pattern than patients with hepatocellular carcinoma. This further reinforces the significance of liver cell dysplasia as a preneoplastic condition. The significantly higher occurrence of variant estrogen receptor in men (especially in HBsAg-positive men) already at an early stage of disease, like chronic active hepatitis, suggests that the alteration of estrogen receptors, favoring uncontrolled proliferation and development of hyperplasia, might constitute a prominent mechanism facilitating neoplastic transformation especially in men.

Portal vein arterialization (PVA) is an acquired concept in shunt surgery for portal hypertension. This technique, recently described as both a temporary and permanent procedure in adult liver transplantation, is reported by the authors in two cases of pediatric transplantation. The indication was low portal blood flow after reperfusion with poor graft function due to persistence of spontaneous retroperitoneal venous shunts. In both cases described, PVA allowed for satisfactory macroscopic liver reperfusion. The increase in portal blood flow from 150 to 500 ml/min in the second patient enabled the liver to be reperfused correctly and led to successful transplantation. The graft function in both cases improved in the 1st postoperative week, but thrombosis of the PVA occurred in the 1st patient 2 months after transplantation. Signs of hepatic hyperarterialization occurred in the second patient and this necessitated a dearterialization of the portal vein 2 weeks later. Although the benefit of this procedure appears to be beyond doubt in the immediate postoperative period, we have no data on long-term arterialization. We do think that PVA can be performed in pediatric liver transplantation, but it may need to be done only in special, individual situations when no valid alternative can be proposed, such as in the absence of a mesenteric vein and/or the presence of spontaneous retroperitoneal venous shunts.

Background. We report on a pilot study investigating the feasibility of early immunosuppression withdrawal after liver transplantation (LT) using antithymocyte globulin (ATG) induction and rapamycin. Methods. LT recipients received 3.75 mg/kg per day ATG from days 0 to 5 followed by rapamycin-based immunosuppression. In the absence of acute rejection (AR), rapamycin was withdrawn after month 4. Immunomonitoring included analysis of peripheral T-cell phenotypes and clonality, cytokine production in mixed lymphocyte reaction, and characterization of intragraft infiltrating cells. Results. Ten patients were enrolled between October 2009 and July 2010. In the first three patients, complete withdrawal of immunosuppression after month 4 led to AR. No further withdrawals of immunosuppressive were attempted. Two AR occurred in the remaining seven patients. ATG induced profound T-cell depletion followed by CD8(+) T-cell reexpansion exhibiting memory/effector-like phenotype associated with progressive oligoclonal T-cell expansion (VA/HPRT ratio) and gradually enhanced anti-cytomegalovirus and anti-Epstein-Barr virus T-cell frequencies. Patients developing AR were characterized by decreased TCAIM expression. AR were associated with increased donor-specific production of interferon (IFN)-gamma and interleukin (IL)-17, increased intragraft expression of IFN-gamma mRNA, and significant CD8(+) T-cell infiltrates colocalizing with IL-17(+) cells. Conclusion. High-dose ATG followed by short-term rapamycin treatment failed to promote early operational tolerance to LT. AR correlates with expansion of memory-type CD8(+) T cells and increased levels of IFN-gamma and IL-17 in mixed lymphocyte reaction and in the graft. This suggests that resistance and preferential expansion of effector memory T-cell in lymphopenic environment could represent the major barrier for establishment of tolerance to LT in approaches using T-cell-depleting induction.

BackgroundAs a consequence of continuous technical developments in liver surgery, laparoscopic liver resection (LLR) is increasingly performed worldwide.MethodsBetween January 2004 and December 2011, 265 LLR were performed in 242 patients for various diseases. The experience of LLR is reported focusing on risk factors of conversion and their management.ResultsThe overall conversion rate was 17/265 (6.4%), equally distributed over the period of the study. Statistically significant factors for conversion were found to be LLR of the postero-superior (P-S) segments (SI, SIVa; SVII; SVIII) (12.7% converted versus 2.5% non-converted groups, P = 0.01) and a major compared with a minor hepatectomy (15.2% vs. 4.6%, P = 0.02 respectively). A R0 resection was achieved in 93.2% of cases. According to Dindo's classification, complications were recorded as grade I (n = 20); grade II (6); grade III (11) and grade IV(1) events (total morbidity rate of 14%). Univariate analysis identified a major hepatectomy and resection involving P-S segments as prognostic factors for conversion whereas multivariate analysis identified the latter as an independent risk factor [P = 0.003, odds ratio (OR) = 5.9, 95% confidence interval (CI) = 1.8-18.8].ConclusionsLLR can be safely performed with low overall morbidity. According to this experience and irrespective of the learning curve, resections of P-S segments were identified as an independent risk factor for conversion in LLR.

Haptoglobin (Hp) is a polymorphic plasma protein with multiple functions defined by three major phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2). In this article, the effects of the donor Hp phenotype (determined by starch gel electrophoresis) on the outcome and the iron status after liver transplantation were investigated. A total of 450 liver transplant patients were enrolled in this study with a median follow-up of 37 months. Kaplan-Meier and Cox regression survival analyses showed a significantly worse graft survival for liver transplantation cases with an Hp 2-2 donor phenotype, which was associated with an increased mortality rate in this group. In male patients, the Hp 2-2 phenotype was associated with higher serum ferritin concentrations, which may be linked to the significantly increased likelihood of infectious complications in this phenotype. Liver transplant patients with Hp 1-1 and Hp 2-1 grafts had a better outcome probability than recipients of an Hp 2-2 graft, which may be explained by differences in iron metabolism induced by the Hp genotype of the graft.

The portal vein flow (PVF), portal vein pressure (PVP), and hepatic venous pressure gradient (HVPG) were prospectively assessed to explore their relationships and to better define hyperflow and portal hypertension (PHT) during liver transplantation (LT). Eighty-one LT procedures were analyzed. No correlation between PVF and PVP was observed. Increases in the central venous pressure (CVP) were transmitted to the PVP (58%, range = 25%-91%, P = 0.001). Severe PHT (HVPG ≥ 15 mm Hg) showed a significant reciprocal association with high PVF (P = 0.023) and lower graft survival (P = 0.04). According to this initial experience, an HVPG value ≥ 15 mm Hg is a promising tool for the evaluation of hemodynamic stress potentially influencing outcomes. An algorithm for graft inflow modulation based on flows, gradients, and systemic hemodynamics is provided. In conclusion, the evaluation of PHT severity with PVP could be delusive because of the influence of CVP. PVF and PVP do not correlate and should not be used individually to assess hyperflow and PHT during LT.

Background Laparoscopic left lateral sectionectomy (LLS) has gained popularity in its use for benign and malignant tumors. This report describes the evolution of the authors’ experience using laparoscopic LLS for different indications including living liver donation. Methods Between January 2004 and January 2009, 37 consecutive patients underwent laparoscopic LLS for benign, primary, and metastatic liver diseases, and for one case of living liver donation. Resection of malignant tumors was indicated for 19 (51%) of the 37 patients. Results All but three patients (deceased due to metastatic cancer disease) are alive and well after a median follow-up period of 20 months (range, 8–46 months). Liver cell adenomas (72%) were the main indication among benign tumors, and colorectal liver metastases (84%) were the first indication of malignancy. One case of live liver donation was performed. Whereas 16 patients (43%) had undergone a previous abdominal surgery, 3 patients (8%) had LLS combined with bowel resection. The median operation time was of 195 min (range, 115–300 min), and the median blood loss was of 50 ml (range, 0–500 ml). Mild to severe steatosis was noted in 7 patients (19%) and aspecific portal inflammation in 11 patients (30%). A median free margin of 5 mm (range, 5–27 mm) was achieved for all cancer patients. The overall recurrence rate for colorectal liver metastases was of 44% (7 patients), but none recurred at the surgical margin. No conversion to laparotomy was recorded, and the overall morbidity rate was 8.1% (1 grade 1 and 2 grade 2 complications). The median hospital stay was 6 days (range, 2–10 days). Conclusions Laparoscopic LLS without portal clamping can be performed safely for cases of benign and malignant liver disease with minimal blood loss and overall morbidity, free resection margins, and a favorable outcome. As the ultimate step of the learning curve, laparoscopic LLS could be routinely proposed, potentially increasing the donor pool for living-related liver transplantation.

Background/aims Placental growth factor (PIGF) is known for its role in pathological conditions to protect parenchymal cells of different organs from injury, whereas its presence in the liver and its potential importance in stimulating liver regeneration has never been described. This was investigated in this study using a rat model of partial hepatectomy (PH). Methods The rat model of 70, 80, and 90% PH was used. Liver samples were taken peroperatively, 1 h, 1, 2, 3, and 7 days after surgery. Liver regeneration was evaluated by liver weight/body weight ratio, liver regeneration rate (%), and proliferating cell marker Ki67. The expression of PIGF, vascular endothelial growth factor (VEGF), VEGF receptor 1 (Flt-1 ), VEGF receptor 2 (Flk-1 and hypoxia inducible factor-1α mRNA was measured by quantitative real-time PCR and localized by immunohistochemistry. Results The mRNA expression of PIGF was upregulated immediately after PH. Compared with 70 and 80% PH groups, the 90% PH group had a significantly lower PIGF and hypoxia inducible factor-1α. mRNA expression, in parallel to a delayed liver weight/body weight ratio recovery. Only little differences were observed in VEGF, Flt-1, and Flk-1 mRNA expression among the PH groups. Conclusion This study shows for the first time the PIGF upregulation in regenerating livers, which is related to hypoxia stimulation and liver growth. The swift PIGF upregulation immediately after PH may indicate an important role for the PIGF/Flt-1 pathway in the early stage of liver regeneration.

New-onset diabetes after transplantation (NODAT) is a frequent complication after liver transplantation and has a negative impact on both patient and graft survival. In analogy with the previous finding of an association between posttransplant hypomagnesemia and NODAT in renal transplant recipients, the relation between both pretransplant and posttransplant hypomagnesemia and NODAT was studied in liver transplant recipients (LTRs). One hundred sixty-nine adult LTRs (>18 years old) without diabetes who underwent transplantation between 2004 and 2009 were studied (mean age = 52.11 ± 12.6 years, proportion of LTRs who were male = 67.5%, body mass index = 25.5 ± 4.4 kg/m², proportion receiving tacrolimus = 90.0%). NODAT was defined according to the American Diabetes Association criteria. The association of NODAT with both pretransplant and posttransplant serum magnesium (Mg) was examined. Overall, 52 of 169 patients (30.8%) developed NODAT, and 57.7% of these (30 patients) were treated with antidiabetic drugs. Both pretransplant Mg levels and Mg levels in the first month after transplantation were lower in patients developing NODAT (P = 0.008 and P = 0.001, respectively). A multivariate regression model (adjusted for weight, pretransplant glucose levels, hyperglycemia in the first week after transplantation, gender, hepatitis C, and corticosteroid dosing) demonstrated both pretransplant Mg levels (hazard ratio = 0.844 per 0.1 mg/dL increase, 95% confidence interval = 0.764-0.932, P = 0.001) and posttransplant Mg levels (hazard ratio = 0.659, 95% confidence interval = 0.518-0.838, P = 0.001) to be independent predictors of NODAT together with age, biopsy-proven acute rejection, and cytomegalovirus (CMV) infection in the first year after transplantation. In conclusion, pretransplant hypomagnesemia and early posttransplant hypomagnesemia are independent predictors of new-onset diabetes after liver transplantation. Other risk factors are age, biopsy-proven acute rejection, and CMV infection.

The Belgian experience with donation after cardiac death (DCD) liver transplantation (LT) was retrospectively reviewed, particularly evaluating patient and graft survivals, and biliary complications. From 2003 to 2007, 58 DCD-LT were performed in Belgium. Mean procurement total warm ischemia time was 25 +/- 2 min (mean +/- SEM). Mean cold ischemia time was 451 +/- 18 min. Mean follow-up was 23 +/- 2.2 months. Post-transplant peak aspartate aminotransminases was 2241 +/- 338 UI/l. Patient survivals at 1 month, 1 and 3 years, were 91.3%, 83.3% and 66.9% respectively. Graft survivals at 1 month, 1 and 3 years, were 84.4%, 72.4% and 48.8% respectively. Two patients (3.4%) developed primary nonfunction. Regarding the biliary complications, seven grafts (12%) were lost because of intrahepatic cholangiopathy, and 12 other patients (20.6%) developed bile duct stenoses requiring endoscopic and/or surgical management. The rate of symptomatic ischemic biliary lesions for grafts surviving more than 3 months was 38% (19/50). Although DCD organ donors may be a source of viable liver grafts, results were inferior to those obtained with donation after brain death LT in this series. Prognostic criteria have to be developed to improve results of DCD-LT.

Split liver transplantation (SLT) is an established technique developed to optimize the number of available grafts. Few data are available on SLT with extended right liver grafts (eRLG) in the context of patient-oriented allocation policy.Between July 1, 2001 and December 31, 2005, 12 whole liver graft (WLG) recipients were matched with 12 eRLG recipients according to their clinical status, indication and year of liver transplantation.There were no differences according to recipient Model for End-stage Liver Disease score, total serum bilirubin, creatinine levels and international normalized ratio in both groups. Fifty percent of donors in eRLG group presented 2 or more extended criteria. Liver transplantation was performed in UNOS status 1/2A in 58% of cases in both groups. Vascular and biliary complications were observed in three patients in the eRLG group. The median follow-up was 25.3 months (range 0.4-63). Early mortality (or=3 m) was 16.7% in WLG vs. 0% in eRLG, respectively (p = n.s.). Five-yr patient and graft survival rates were 84% and 77%, and 75% and 68%, respectively, for WLG and eRLG.Split liver transplantation with eRLG according to the patient-oriented allocation policy can be performed under emergency or urgent care circumstances with acceptable morbidity and adequate long-term survival.

Living donors represent a recognized alternative for facilitating the access to transplantation in a period of organ shortage. However, which candidates should be preferentially considered for living-donor liver transplantation (LDLT) is debated. The aim of this study was to create statistical models to determine which strategies of selection for LDLT provide the most efficient contribution. The study included 331 patients listed for deceased-donor transplantation (DDLT) and 128 transplanted with living donors. Statistical models predicting the events following listing were created and combined in a multistate model allowing the testing of different strategies of selection for LDLT and to compare their results. Taking 3-yr survival after listing as the principal end-point, selecting the 20% patients at highest risk of death on the waiting list gave better results than selecting the 20% patients at lowest risk of death after LDLT (70% vs. 64%, respectively). These strategies resulted in waiting list mortality rates of 17% and 8%, respectively. One-year survival after LDLT was lower in high-risk patients (85%) than in low-risk patients (91%). However, the 1-yr survival benefit derived from LDLT was 75% in high-risk patients while it was nil in low-risk patients. In conclusion, LDLT is more effective for overcoming the consequences of organ shortage when performed in patients at high risk of death on the waiting list. On an individual basis, the sickest patients are those who derive the most important benefit from LDLT. This study provides incentives for considering LDLT in high-risk patients.

ABO-incompatible (ABO-I) liver transplantation is a controversial issue because of the generally less favorable outcome as compared to compatible transplants. Encouraging results have been shown by the introduction of new strategies to reduce posttransplant-specific hemagglutinin (HA) titers with plasmapheresis, reinforced immunosuppression (IS), and the use of splenectomy. We describe a new protocol consisting of daclizumab (DAC) induction, mycophenolate mofetil (MMF)/tacrolimus (TAC)/steroids without splenectomy. Five recipients (mean age of 47 14 yr) undergoing ABO-I living donor liver transplantation (LDLT) were included in this protocol. Immunoadsorbent columns (Glycosorb ABO) were used for antigenspecific immunoadsorption (ASI). The median follow-up was 18.5 10.5 months. ASI was very efficient in lowering HA titers (mean log2 immunoglobulin [Ig] M [IgM] and IgG values before and after ASI were 5.9 2.8 and 1.2 1.4 [P 0.0038] and 6.5 2.3 and 1.1 1.9, respectively [P 0.0001]). Persisting low HA titers were observed over time. No sepsis nor cytomegalovirus infection episodes were recorded. Acute cellular rejection (ACR) occurred in 1 recipient responding to steroid pulse therapy. Two grafts were lost in 2 patients due to technical failure during the first postoperative month. We conclude that ASI using Glycosorb ABO, quadruple immunosuppression including DAC and MMF provide high efficiency to lower HA titers over time, avoiding the need for splenectomy. ABO-I LDLT can be performed with this adapted IS protocol. Liver Transpl 12: 1412–1417, 2006. © 2006 AASLD.

New immunosuppressive agents and regimens should be evaluated specifically in living donor liver transplant patients due to potential clinical and pharmacokinetic differences between deceased donor and living donor transplant recipients. The analysis presented here is the first direct comparison of clinical outcomes using cyclosporine microemulsion (CsA-ME) with monitoring of blood concentration at 2 hours postdose (C2) and tacrolimus-based immunosuppression in living donor liver transplantation. The analysis was conducted on the data provided by the 39 recipients of a living donor transplant out of the 495 patients enrolled in a 6-month, randomized, prospective, multicenter, open-label study (LIS2T). Patients were randomized to CsA-ME (C2 monitoring) or tacrolimus (monitoring of predose trough drug blood level [C0)]) and were administered corticosteroids with or without azathioprine. Twenty-three living-donor patients received CsA-ME and 16 received tacrolimus. By month 6, 9% of patients receiving CsA-ME and 19% of those receiving tacrolimus had lost their graft or died (not significant [NS]). Nine episodes of biopsy-proven acute rejection were reported: 4 in the CsA-ME group (17%) and 5 in the tacrolimus cohort (31%, NS). There were no significant differences in any safety parameter between groups. The most frequently reported serious adverse events were infections, which occurred in 14 patients in the CsA-ME group (61%) and 13 patients in the tacrolimus arm (81%, NS). Twelve patients in the CsA-ME arm (52%) and 5 in the tacrolimus arm (31%, NS) discontinued the study prematurely. In conclusion, CsA-ME C2 monitoring or tacrolimus both offer effective protection against rejection in living donor liver transplants while maintaining a good safety profile.

Background Chronic hepatitis B (HBV) and hepatitis C (HCV) patients have elevated plasma levels of soluble CD14 (sCD14). We examined whether human hepatocytes produce sCD14 in vivo, and whether HBV or HCV infections influence this chimeric production. Methods uPA-SCID mice were transplanted with primary human hepatocytes and some animals were subsequently infected with HBV or HCV. Plasma from these mice was analyzed for the presence of human sCD14. The liver was examined via immunohistochemistry. Results A soluble form of human CD14 could be detected in the plasma from successfully transplanted mice, while it was completely absent in non-transplanted control animals. The isoform of this human sCD14 corresponded with the most abundant isoform found in human plasma. CD14 levels in circulation were not significantly different between non-infected, HBV infected and HCV infected animals. Conclusions Our data indicate that human hepatocytes produce sCD14 in vivo, and that liver cells might be the major source of sCD14 in normal human plasma. In addition we demonstrate that HBV and HCV infections have no direct influence on the production of sCD14 by human hepatocytes in this chimeric model.

Graft hyperperfusion in small-for-size grafts (SFSG) is considered the main causal factor of small-for-size syndrome (SFSS). We compared SFSG with a graft-to-recipient body ratio < or =0.8, with and without graft inflow modulation (GIM) by means of a hemi-portocaval shunt (HPCS). Thirteen patients underwent adult-to-adult living donor liver transplantation (AALDLT): G1, n = 5 [4 right livers (RL) and 1 left liver (LL)] without GIM, and G2, n = 8 (4 RL and 4 LL) with GIM. In G2 patients, portal vein flow (PVF) was significantly reduced by HPCS: 190 +/- 70 mL/min/100 g liver in G2 vs. 401 +/- 225 ml/min in G1 (p = 0.002). One- and 6-month post-transplantation graft volume/standard liver volume (GV/SLV) ratio was of 72% and 79.5% in G1; 80% and 101% in G2 (p = ns). SFSS was observed in three G1 recipients (who were retransplanted), but in none of the G2 patients. At 1-year, patient and graft survival was respectively of 40% and 20% in G1, 87.5% and 75% in G2 (p = 0.024 and 0.03). It is concluded that drastic reduction of PVF by means of HPCS improves overall patient and graft survival by averting the occurrence of SFSS. Graft inflow modulation through HPCS reduces the risk of complications when transplanting SFSG in adult recipients.

Background: Liver transplantation has become an important curative treatment option for hepatocellular carcinoma (HCC). Criteria for transplantation are strict and, therefore, it is crucial that patients awaiting transplantation do not suffer disease progression. One of the therapeutic options to achieve disease stabilization is neoadjuvant radiolabeled lipiodol treatment. This study aimed to document the dropout rate on the waiting list, the pathological findings on the explant livers, and the long-term outcome of patients treated. with radionuclide therapy while awaiting transplantation. Methods: Patients eligible for transplantation were treated with 2.1 GBq I-131-lipiodol or 4.1 GBq Re-188-HDD/lipiodol by transfemoral catheterization of the hepatic arteries. Tumor necrosis was assessed in the explant livers and,follow-up data, such as dropout from the waiting list, recurrence, and survival following transplantation were retrospectively documented. Results: In 5 of 22 explants, necrosis exceeded 90%. Two patients died while, on the waiting list (10%) and 4 of 20 transplanted patients (20%) suffered recurrent disease. The overall recurrence-free survival was 19.7 months (range, 1.75-56), with a mean follow-up of 20. 1 months. Conclusion: Our data support the evaluation on larger patient numbers to confirin the benefit of radiolabeled lipiodol in candidates for liver transplantation who are suffering from HCC.

A small animal model harboring a functional human liver cell xenograft would be a useful tool to study human liver cell biology, drug metabolism, and infections with hepatotropic viruses. Here we describe the repopulation, organization, and function of human hepatocytes in a mouse recipient and the infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) of the transplanted cells. Homozygous urokinase plasminogen activator (uPA)-SCID mice underwent transplantation with primary human hepatocytes, and at different times animals were bled and sacrificed to analyze plasma and liver tissue, respectively. The plasma of mice that were successfully transplanted contained albumin and an additional 21 human proteins. Liver histology showed progressive and massive replacement of diseased mouse tissue by human hepatocytes. These cells were accumulating glycogen but appeared otherwise normal and showed no signs of damage or death. They formed functional bile canaliculi that connected to mouse canaliculi. Besides mature hepatocytes, human hepatic progenitor cells that were differentiating into mature hepatocytes could be identified within liver parenchyma. Infection of chimeric mice with HBV or HCV resulted in an active infection that did not alter the liver function and architecture. Electron microscopy showed the presence of viral and subviral structures in HBV infected hepatocytes. In conclusion, human hepatocytes repopulate the uPA(+/+)-SCID mouse liver in a very organized fashion with preservation of normal cell function. The presence of human hepatic progenitor cells in these chimeric animals necessitates a critical review of the observations and conclusions made in experiments with isolated "mature" hepatocytes. Supplementary material for this article can be found on the HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html).

A new carrier-bound fibrin sealant, TachoSil, is expected to be efficacious and safe as a haemostatic treatment in hepatic resection. A prospective, randomised, open and controlled multicentre trial with intraoperative as well as postoperative assessment of efficacy and a 1 month follow-up period. Tertiary care centres. One hundred and twenty-one patients requiring secondary haemostasis during planned liver resection. Patients with coagulation disorders and patients with persistent major bleeding after primary haemostatic measures were excluded. Application of either carrier-bound fibrin sealant (n=59) or argon beamer (argon beam coagulator) (n=62) as secondary haemostatic treatment. Time to intraoperative haemostasis. There was a significant superiority of TachoSil over argon beamer with regard to time to haemostasis (3.9 min, median 3.0, range 3–20 min vs 6.3 min, median 4.0, range 3–39 min) (P=0.0007). Haemoglobin concentration of drainage fluid was significantly lower on day 2 after surgery in TachoSil patients (1.1 mmol/l) than in argon beamer patients (2.3 mmol/l) (P=0.012). Overall, the frequency and causality of adverse events did not differ between the two treatment groups. TachoSil is superior to argon beamer in obtaining effective and fast intraoperative haemostasis. The safety data show TachoSil to be tolerable and safe for haemostatic treatment in liver resection.