As soon as deceased donor liver transplantation (DDLT) became a standard clinical practice, the disparity between the constantly growing number of liver transplant candidates and the supply of deceased donor organs highlighted the need for new solutions, opening the era of living donor liver transplantation (LDLT). The first preparatory experiences for the development of LDLTs were pushed by the shortage of pediatric liver grafts that was even more marked. The first step of this process was the reduced-size liver transplantation, performed by Bismuth and Houssin (1984), followed by the first reduced liver grafts transplanted in children by de Hemptinne et al. (1987). Based on this concept, split-graft liver transplantation was then developed and reported in 1990 by the Broelsch group in Chicago, confirming the possibility to treat more recipients with one liver graft limiting graft size problems (Emond et al., 1990; Pichlmayr et al., 1988). Following these pioneering works, LDLT has spread throughout the world becoming an established procedure in case of not available grafts from deceased donors, representing the standard of care liver transplant technique in Asia. Nevertheless, LDLT is characterized by technical complexity, as well as peculiar clinical and ethical aspects.

Abstract 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% (P = 0.01 and P = 0.024, respectively) while SFSS was associated with a recipient MELD ≥14 (P = 0.019). A combination of donor age <45 years, MELD <14 and actual 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 70.5 months, 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.

BACKGROUND:As a consequence of continuous technical developments in liver surgery, laparoscopic liver resection (LLR) is increasingly performed worldwide.METHODS:Between 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.RESULTS:The 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].CONCLUSIONS:LLR 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.

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 (Vβ/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)-γ and interleukin (IL)-17, increased intragraft expression of IFN-γ 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-γ 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.

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 secondary 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 was 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. (Surgery 2011;149:48-55.)

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. Liver Transpl 17:836-848, 2011. © 2011 AASLD.

Background/aims Placental growth factor (PlGF) 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 PlGF, 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 PlGF was upregulated immediately after PH. Compared with 70 and 80% PH groups, the 90% PH group had a significantly lower PlGF 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 PlGF upregulation in regenerating livers, which is related to hypoxia stimulation and liver growth. The swift PlGF upregulation immediately after PH may indicate an important role for the PlGF/Flt-1 pathway in the early stage of liver regeneration.

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.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.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).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: 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.METHODS: 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 chi(2) test and Fisher's exact test were used to assess the differences between categorical data. P values < .05 were considered statistically significant.RESULTS: 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 1(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 I year.CONCLUSIONS: 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. (C) 2011 Elsevier Inc. All rights reserved.

Background With the introduction of a self-expanding, memory-containing, circular hernia patch, surgeons have been enthusiastic about its use to repair ventral hernias smaller than 3 cm in diameter. The aim of this study was to evaluate the efficiency, reliability, and safety of the device laparoscopically with respect to adequate deployment of the patch.Methods During 1 year all patients with small ventral hernias were treated with this memory-containing patch and were inspected by laparoscopy. Just prior to insertion of the patch, remaining adhesions on top of the peritoneum were analyzed, as was the interference of the umbilical ligament. The final position of the patch was monitored, identifying the cupping phenomenon, exposure of the polypropylene to the viscera, and the amount of tension on the straps. All patients were followed for 2 years and postoperative complications and recurrence rate were monitored.Results Twenty-eight patients were operated on for repair of a small ventral hernia with laparoscopic control. Adhesions, not digitally palpable, that interfered with adequate patch deployment were observed in more than 80% of the cases. After a median follow-up of 25 months a 14.8% recurrence rate was observed.Conclusions The patch, consisting of both polypropylene and ePTFE, leads to unacceptable morbidity and a high rate of recurrences. By laparoscopic evaluation, these recurrences are probably based on a combination of material characteristics and unavoidable technical errors.

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.