Full-size Liver Research Articles

Laparoscopic-assisted full-sized liver transplantation with magnetically fast portal vein anastomosis: an initial cohort study.

Some cases of laparoscopic-assisted liver transplantation (LA-LT) with utilization of reduced-size grafts has been reported. The authors here introduced successful utilization of LA-LT with whole liver grafts and magnetic portal vein anastomosis. Eight patients with liver cirrhosis were included for LA-LT using donor organs after cardiac death. The surgical procedures included purely laparoscopic explant hepatectomy and whole-liver graft implantation via the midline incision. After explant removal, the whole-liver graft was then placed in situ, and a side-to-side cavo-caval anastomosis with 4-5cm oval opening was performed. The magnetic rings were everted on the donor and recipient portal vein, respectively, and the instant attachment of the two magnets at the donor and recipient portal vein allowed fast blood reperfusion, followed by continuous suturing on the surface of the magnets. The median operation time was 495 (range 420-630). The median time of explant hepatectomy and inferior vena cava anastomosis was 239 (range 150-300) min and 14.5 (range 10-19) min, respectively. Of note, the median anhepatic time was 25 (range 20-35) min. All the patients were discharged home with no major complications after more than 12 months follow-up. LA-LT with full-size graft is feasible and utilization of magnetic anastomosis would further simplify the procedure.

Laparoscopic-assisted full-sized liver transplantation with magnetically fast portal vein anastomosis

Laparoscopic-assisted full-sized liver transplantation with magnetically fast portal vein anastomosis

Effect of a Combined Drug Approach on the Severity of Ischemia-Reperfusion Injury During Liver Transplant

In a porcine model of liver transplant, a combined drug approach that targeted the donor graft and graft recipient reduced ischemia-reperfusion injury, a major hurdle to the success of liver transplant. To assess the effect of a clinical form of a perioperative combined drug approach delivered immediately before implantation to the procured liver and to the liver recipient on the degree of ischemia-reperfusion injury. This unicentric, investigator-driven, open-label randomized clinical trial with 2 parallel arms was conducted in Belgium from September 2013 through February 2018, with 1-year follow-up. Adults wait-listed for a first solitary full-size liver transplant were screened for eligibility. Exclusion criteria were acute liver failure, kidney failure, contraindication to treatment, participation in another trial, refusal, technical issues, and death while awaiting transplant. Included patients were enrolled and randomized at the time of liver offer. Data were analyzed from May 20, 2019, to May 27, 2020. Participants were randomized to a combined drug approach with standard of care (static cold storage) or standard of care only (control group). In the combined drug approach group, following static cold preservation, donor livers were infused with epoprostenol (ex situ, portal vein); recipients were given oral α-tocopherol and melatonin prior to anesthesia and intravenous antithrombin III, infliximab, apotransferrin, recombinant erythropoietin-β, C1-inhibitor, and glutathione during the anhepatic and reperfusion phase. The primary outcome was the posttransplant peak serum aspartate aminotransferase (AST) level within the first 72 hours. Secondary end points were the frequencies of postreperfusion syndrome, ischemia-reperfusion injury score, early allograft dysfunction, surgical complications, ischemic cholangiopathy, acute kidney injury, acute cellular rejection, and graft and patient survival. Of 93 randomized patients, 21 were excluded, resulting in 72 patients (36 per study arm) in the per protocol analysis (median recipient age, 60 years [IQR, 51.7-66.2 years]; 52 [72.2%] men). Peak AST serum levels were not different in the combined drug approach and control groups (geometric mean, 1262.9 U/L [95% CI, 946.3-1685.4 U/L] vs 1451.2 U/L [95% CI, 1087.4-1936.7 U/L]; geometric mean ratio, 0.87 [95% CI, 0.58-1.31]; P = .49) (to convert AST to μkat/L, multiply by 0.0167). There also were no significant differences in the secondary end points between the groups. In this randomized clinical trial, the combined drug approach targeting the post-cold storage graft and the recipient did not decrease ischemic-reperfusion injury. The findings suggest that in addition to a downstream strategy that targets the preimplantation liver graft and the graft recipient, a clinically effective combined drug approach may need to include an upstream strategy that targets the donor graft during preservation. Dynamic preservation strategies may provide an appropriate delivery platform. ClinicalTrials.gov Identifier: NCT02251041.

The Authors' Reply: Organoid Technology: Are Human Cholangiocyte Organoids Immune Protected?

We thank Ekser et al1 for reading our commentary2 on the groundbreaking Science publication by Sampaziotis et al3 on repair of bile ducts after transplantation of cholangiocyte organoids in human liver grafts. Ekser et al1 comment that if allogenic cholangiocyte organoids would be used for graft repair, this potentially can provoke an alloimmune response. The authors are “puzzled by the outcome of the original paper3 as nonautologous organoids were used and no protective immunosuppressive medication is used during the normothermic machine perfusion of the liver grafts.” Indeed, cholangiocytes or cholangiocyte organoids, in this matter, are not blinded from the immune system as they normally express major histocompatibility complexes (HLA) on their cell surface. However, in this study, like many studies with human liver normothermic machine perfusion,4 leukocyte-depleted packed red blood cells in gelofusine were used for oxygenation of the graft and therefore completely lacked alloreactive immune cells. Therefore, no acute rejection of the engrafted organoids was observed, even despite no immunosuppressive treatment was given. In case such a cell-therapy repaired graft would be actually transplanted, immunosuppressive medication is inevitably needed to prevent rejection of the donor allograft and the third party allogenic organoid cell alike. Exposing the immune system to extra allogenic cells might nonetheless increase the risk of an alloimmune response. Therefore, as mentioned in our Game Changer commentary: “For graft repair, ideally, autologous cells of the recipient should be used to diminish the risk of alloimmune responses.”2 Safe means to obtain autologous cells for organoid initiation are required. Indeed, cholangiocyte organoids can now be cultured from liver fine-needle aspiration biopsies or from bile, obtained via percutaneous drainage of the gallbladder or via endoscopic retrograde cholangiopancreatography,5 with very limited risks. The future recipient’s cholangiocyte organoids could thus be stored in a biobank at enlistment for liver transplantation, making patient-derived cells directly available for regenerative purposes at the time of a donor liver offer. The bottleneck in using autologous cholangiocyte organoids is not so much culturing the recipient’s own cells but the logistics of having sufficient numbers of cells at the moment of transplantation. Sampaziotis et al3 used approximately 10 million cells for injecting single liver segment 3. To treat the whole graft, at least 10 times this number of cells would be required to treat the entire biliary tree of a full-size liver. To reach high amounts of organoid cells in a short time, more efficient culturing methods are being developed.6 Cryopreservation protocols should be optimized to store large quantities of cholangiocyte organoids, which could be directly administered to the liver after thawing. Taken together, we consider that ideally, autologous cells should be used in graft repair to minimize the risk of an alloimmune response. Logistic problems need to be solved before this regenerative approach can be clinically implemented. We foresee that this way of repairing the biliary tree will evolve from bench to bedside in the upcoming years.

Outcome of Extended Right Lobe Liver Transplantations.

Split-liver transplantation offers a solution to the organ shortage problem. However, the outcomes of extended right lobe liver transplantation (ERLT) and whether it is a suitable alternative to full-size liver transplantation (FSLT) remain controversial. We compared the outcomes of ERLT and FSLT in adult recipients of 43,409 first deceased donor liver transplantations using Cox regression. We also analyzed 612 ERLT and 1224 FSLT 1:2 matched cases to identify factors that affect ERLT outcome. The risk of graft loss was significantly higher following ERLT than following FSLT during the first posttransplantation year in the matched and unmatched collective (hazard ratio [HR], 1.39 and 1.27 and P=0.01 and 0.006, respectively). Every additional hour of cold ischemia time (CIT) increased the risk of 1-year graft loss by 10% in the ERLT group compared with only 3% in the FSLT group (P=0.003 and <0.001, respectively). Importantly, the outcome of ERLT and FSLT did not differ significantly if the CIT was below 10hours (HR, 0.71; P=0.22). One-year graft and patient survival were lower in high-risk ERLT recipients with a Model for End-Stage Liver Disease (MELD) score of ≥20 (HR, 1.88; P=0.03 and HR, 2.03; P=0.02). In the male recipient-male donor combination, ERLT recipients had a higher risk of 1-year graft loss than FSLT recipients (HR, 2.44; P=0.006). This was probably because of the significantly higher MELD score in ERLT recipients (P=0.004). ERLT in adults is an adequate alternative to FSLT and offers an elegant solution to the problem of organ shortage as long as the cold storage is less than 10hours and the recipient's MELD score is <20.

THE FIRST CASE OF SIMULTANEOUS DECEASED DONOR LIVER AND KIDNEY TRANSPLANTATION IN AN HIV/HCV CO-INFECTED PATIENT WITH HEMOPHILIA IN JAPAN

We herein describe for the first case of simultaneous liver and kidney transplantation (SLK) in an HCV/HIV-coinfected patient with severe hemophilia in Japan. The patient was a 61-year-old Japanese man with HCV cirrhosis. He was diagnosed with haemophilia B at age 1 year. He was infected with HCV and HIV due to imported contaminated blood products. The patient’s liver disease was classified as Child-Pugh C, Model for End-Stage Liver Disease score 38. He had been on hemodialysis for 6 years, but both HIV RNA and HCV RNA had been undetectable after appropriate antiviral therapies. In September 2019, the patient underwent successful SLK. The donor was a man in 60’s deceased due to cerebral hemorrhage. Regular DDLT was performed using the piggyback technique with a full-sized liver graft. Cold ischemia time was 566 min, and the graft liver weighed 1,154 g. The graft kidney was transplanted extraperitoneally in the right iliac fossa. A total of 76 U of packed red cells and 100 U of fresh frozen plasma were infused during the 12-h procedure, which required packing and subsequent depaking procedure on day3. Also, the administration of clotting factor IX discontinued on day 3. The immunosuppressive regimen was based on i.v. induction with 2 mg/kg of basiliximab and 1g methylprednisolone and subsequent oral administration of mycophenolate mofetil and prednisolone, followed by low dose taclorimus after 1w for kidney sparing purpose. Steroid therapy was gradually discontinued at 3 months after SLK. The same pretransplantation antiretroviral therapy (ART; tenofovir and doltegravir) was introduced after 3 days when the CD4 cell count was more than 300/μl and HIV-RNA was within undetectable range. The postoperative course was uneventful without infectious complication, and the patient was transferred to referral hospital on day 90 and discharged home on day 111. Herein, we report the first case of SLK for HIV/HCV co-infected hemophilic patient in Japan. Strategic surgical planning and meticulous pre and post-transplant management of ART and clotting factors could lead to the success of SLK.

Simultaneous Deceased Donor Liver and Kidney Transplantation in a Human Immunodeficiency Virus/Hepatitis C Virus -Coinfected Patient With Hemophilia in Japan: A Case Report

The authors describe the first case of simultaneous liver and kidney transplantation (SLK) in a human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patient with severe hemophilia in Japan, and it could be second case in the world. The patient was a 61-year-old Japanese man with HCV cirrhosis complicated with HIV coinfection through contaminated blood product for hemophilia B at age 1 year. The patient’s liver disease was classified as Child-Pugh C, Model for End-Stage Liver Disease score 38. He had been on hemodialysis for 6 years, but HIV RNA and HCV RNA had been undetectable after appropriate antiviral therapies. In September 2019, the patient underwent successful deceased donor (DD) SLK. The donor was a man in his 60s deceased due to cerebral hemorrhage. Regular DD liver transplantation was performed using the piggyback technique with a full-sized liver graft. Cold ischemia time was 566 min, and the graft liver weighed 1154 g. The graft kidney was transplanted extraperitoneally in the right iliac fossa. The administration of clotting factor IX was discontinued on day 3. The immunosuppressive regimen was based on intravenous induction with 2 mg/kg of basiliximab and 1 g methylprednisolone and subsequent oral administration of mycophenolate mofetil and prednisolone, followed by low-dose tacrolimus after 1 week for kidney-sparing purpose. Steroid therapy was gradually discontinued at 3 months after SLK. The same pretransplantation antiretroviral therapy (ART; tenofovir and dolutegravir) was introduced after 3 days when the CD4 cell count was more than 300/μL and HIV RNA was within an undetectable range. The postoperative course was uneventful without infectious complication, and the patient was transferred to a referral hospital on day 90 and discharged home on day 111. Strategic surgical planning and meticulous pre- and post-transplant management of ART and clotting factors could lead to the success of SLK.

Biliary complications in liver transplantation: Impact of anastomotic technique and ischemic time on short- and long-term outcome.

To elucidate the impact of various donor recipient and transplant factors on the development of biliary complications after liver transplantation. We retrospectively reviewed 200 patients of our newly established liver transplantation (LT) program, who received full size liver graft. Biliary reconstruction was performed by side-to-side (SS), end-to-end (EE) anastomosis or hepeaticojejunostomy (HJ). Biliary complications (BC), anastomotic stenosis, bile leak, papillary stenosis, biliary drain complication, ischemic type biliary lesion (ITBL) were evaluated by studying patient records, corresponding radiologic imaging and reports of interventional procedures [e.g., endoscopic retrograde cholangiopancreatography (ERCP)]. Laboratory results included alanine aminotransferase (ALT), gammaglutamyltransferase and direct/indirect bilirubin with focus on the first and fifth postoperative day, six weeks after LT. The routinely employed external bile drain was examined by a routine cholangiography on the fifth postoperative day and six weeks after transplantation as a standard procedure, but also whenever clinically indicated. If necessary, interventional (e.g., ERCP) or surgical therapy was performed. In case of biliary complication, patients were selected, assigned to different complication-groups and subsequently reviewed in detail. To evaluate the patients outcome, we focussed on appearance of postoperative/post-interventional cholangitis, need for rehospitalisation, retransplantation, ITBL or death caused by BC. A total of 200 patients [age: 56 (19-72), alcoholic cirrhosis: n = 64 (32%), hepatocellular carcinoma: n = 40 (20%), acute liver failure: n = 23 (11.5%), cryptogenic cirrhosis: n = 22 (11%), hepatitis B virus /hepatitis C virus cirrhosis: n = 13 (6.5%), primary sclerosing cholangitis: n = 13 (6.5%), others: n = 25 (12.5%) were included. The median follow-up was 27 mo until June 2015. The overall biliary complication rate was 37.5% (n = 75) with anastomotic strictures (AS): n = 38 (19%), bile leak (BL): n = 12 (6%), biliary drain complication: n = 12 (6%); papillary stenosis (PS): n = 7 (3.5%), ITBL: n = 6 (3%). Clinically relevant were only 19% (n = 38). We established a comprehensive classification for AS with four grades according to clinical relevance. The reconstruction techniques [SS: n = 164, EE: n = 18, HJ: n = 18] showed no significant impact on the development of BCs in general (all n < 0.05), whereas in the HJ group significantly less AS were found (P = 0.031). The length of donor intensive care unit stay over 6 d had a significant influence on BC development (P = 0.007, HR = 2.85; 95%CI: 1.33-6.08) in the binary logistic regression model, whereas other reviewed variables had not [warm ischemic time > 45 min (P = 0.543), cold ischemic time > 10 h (P = 0.114), ALT init > 1500 U/L (P = 0.631), bilirubin init > 5 mg/dL (P = 0.595), donor age > 65 (P = 0.244), donor sex (P = 0.068), rescue organ (P = 0.971)]. 13% (n = 10) of BCs had no therapeutic consequences, 36% (n = 27) resulted in repeated lab control, 40% (n = 30) received ERCP and 11% (n = 8) surgical therapy. Fifteen (7.5%) patients developed cholangitis [AS (n = 6), ITBL (n = 5), PS (n = 3), biliary lesion BL (n = 1)]. One patient developed ITBL twelve months after LT and subsequently needed retransplantation. Rehospitalisation rate was 10.5 % (n= 21) [AS (n = 11), ITBL (n = 5), PS (n = 3), BL (n = 1)] with intervention or reinterventional therapy as main reasons. Retransplantation was performed in 5 (2.5%) patients [ITBL (n = 1), acute liver injury (ALI) by organ rejection (n = 3), ALI by occlusion of hepatic artery (n = 1)]. In total 21 (10.5%) patients died within the follow-up period. Out of these, one patient with AS developed severe fatal chologenic sepsis after ERCP. In our data biliary reconstruction technique and ischemic times seem to have little impact on the development of BCs.

Incidence of heparin-induced thrombocytopenia type II and postoperative recovery of platelet count in liver graft recipients: a retrospective cohort analysis

BackgroundThrombocytopenia in patients with end-stage liver disease is a common disorder caused mainly by portal hypertension, low levels of thrombopoetin, and endotoxemia. The impact of immune-mediated heparin-induced thrombocytopenia type II (HIT type II) as a cause of thrombocytopenia after liver transplantation is not yet understood, with few literature citations reporting contradictory results. The aim of our study was to demonstrate the perioperative course of thrombocytopenia after liver transplantation and determine the occurrence of clinical HIT type II. MethodWe retrospectively evaluated the medical records of 205 consecutive adult patients who underwent full-size liver transplantation between January 2006 and December 2010 due to end-stage or malignant liver disease. Preoperative platelet count, postoperative course of platelets, and clinical signs of HIT type II were analyzed. ResultsA total of 155 (75.6%) of 205 patients had thrombocytopenia before transplantation, significantly influenced by Model of End-Stage Liver Disease score and liver cirrhosis. The platelet count exceeded 100,000/μL in most of the patients (n = 193) at a medium of 7 d. Regarding HIT II, there were four (1.95%) patients with a background of HIT type II. ConclusionsThe incidence of HIT in patients with end-stage hepatic failure is, with about 1.95%, rare. For further reduction of HIT type II, the use of intravenous heparin should be avoided and the prophylactic anticoagulation should be performed with low-molecular-weight heparin after normalization of platelet count.

PTU-057 Split liver transplant recipients are less likely to require peri-operative renal replacement therapy than full-size liver transplant controls

IntroductionSeveral small studies have suggested that split liver transplant (SLT) recipients have an increased frequency of peri-operative acute kidney injury (AKI). However, given that hepatic ischaemia-reperfusion injury may play a...

Influence of Hematopoietic Stem Cell-Derived Hepatocytes on Liver Regeneration after Sex-Mismatched Liver Transplantation in Humans

ABSTRACTBackground: Presence of hematopoietic stem-cell-derived hepatocytes after clinical liver transplantation was demonstrated repeatedly. The relevance of this controversial mechanism of regeneration was discussed. Regarding frequency, the demonstrated results were divergent. In the present study, we propose to investigate the influence of growth and regeneration on the frequency of hematopoietic stem-cell-derived hepatocytes in transplanted organs. Material and Method: Paraffin-embedded liver specimens, obtained as clinically indicated, from female grafts transplanted into male recipients were investigated. The presence of Y-chromosome in hepatocytes, detected by fluorescence in situ hybridization (FISH), was the indicator for recipient origin. Slides were evaluated by assessing the relative number of Y-chromosome containing hepatocytes within 50 images representing an average of 775 hepatocytes. Results: In only 9 out of 81 specimens, single Y-chromosome positive hepatocytes were detected, resulting in a maximal frequency of 0.64%. Six positive specimens were obtained from full-size liver grafts and one from a partial liver graft. In the pediatric group, two positive samples were found. By staining additional sections from the nine positive specimens, no additional positive hepatocytes were detected suggesting an even lower frequency within the whole sample. We did not find any accumulation of Y-chromosome positive cells in any of the individually analyzed patient groups. Conclusion: Transdifferentiation of hematopoietic stem cells is an extremely rare event in liver growth and regeneration after transplantation. Due to the low number of positive events, the biological relevance seems questionable.

Comparison of immediate renal dysfunction in split and partial liver transplantation versus full size liver transplantation in Shiraz transplant centre

Renal dysfunction (RD) is a common complication following liver transplantation. Postoperative renal function after split liver transplant (SLT) and (partial living related liver transplant) (LRLT) has not been well studied yet. Renal function immediately after surgery was analyzed retrospectively in 32 patients that received SLT and LRLT. Serum creatinine (SCr) was measured before surgery, and, after transplantation daily during the first week and at 14, 21, and 28 days after transplantation. Patient's medical records were reviewed to find clinical data;Model for end-stage liver disease (MELD) score, Child-Turcotte-Pugh score (CTP) class, the length of surgery, length of anhepatic phase, hospital and ICU admission, incidence of acute rejection, renal dysfunction, and sepsis. These data compared between groups. Length of surgery and anhepatic phase was longer in SLT and LRLT group (P<0.05). The incidence of acute rejection, reoperation, and complication such as sepsis was higher in SLT and LRLT group than FSLT group (P<0.05). There were no significant difference between groups with respect to MELD, CTP score, the need for transfusions, the length of admission to the hospital and ICU. Immunosuppression regimens were similar in both groups. RD developed in 25.8% of SLT and LRLT patients, but in only 9.5% of FSLT patients (p=0.063). The requirement for RRT in SLT and LRLT group (12.5%) was greater than that in the FSLT group (2.3%); P=0.20. Although the number of patients studied was small, our data suggests a higher incidence of RD in patients receiving SLT and LRLT.

Successful outcome after early combined liver and en bloc‐kidney transplant in an infant with primary hyperoxaluria type 1: A case report

PH1 is a metabolic disorder characterized by urolithiasis and the accumulation of oxalate crystals in the kidneys and other organs. Although patients often first present with renal failure, PH1 results from a deficiency of the hepatic peroxisomal enzyme AGT. Ultimately only liver transplantation will cure the underlying metabolic defect. Herein, we report the case of a three-month-old male infant diagnosed with PH and treated using a combined liver and en bloc-kidney transplant from a single donor. At the time of transplant, the patient was 11 months old and weighed 7.9 kg. He received a full size liver graft and en bloc kidneys from a two-yr-old donor. At 36 months post-transplant, the patient is steadily growing with normal renal and hepatic function. This is one of the first reports of successful liver and en bloc-kidney transplantation with abdominal compartment expansion by PTFE for the infantile form of PH1 in a high risk child before one yr of age. Prompt diagnosis and early referral to a specialized center for liver and kidney replacement offer the best chance for survival for infants with this otherwise fatal disease.

Oral Tacrolimus Bioavailability Is Increased After Right Split Liver Transplantation

Objective Tacrolimus (Tac) is mainly metabolized in the liver. The aim of this trial was to analyze Tac bioavailability after partial liver transplantation. Patients and Methods A total of 33 patients after right split liver grafting (n = 8 living related, LRLT; n = 8 cadaver split, CS) or full-size liver transplantation (n = 17, FS) were included in this trial. All of them received Tac perorally with an initial dose of 2 × 5 mg/d. Dose adjustment was performed according to the Tac trough level (T0) with an initial target T0 levels of 12 to 15 ng/mL. Results The time to reach target T0 levels tended to be lower ( P = .05) in the split liver groups (LRLT: 2.8 ± 1.6 days; CS: 2.1 ± 0.9 days; FS: 4.5 ± 3.2 days). In addition, mean Tac dose to maintain the target T0 level was significantly decreased ( P = .01) in the split liver cohorts (LRLT: 5.8 ± 1.1 mg/d; CS: 5.5 ± 2.5 mg/d; FS: 9.8 ± 3.9 mg/d). Only graft weight/standard liver volume ratio ( r = .566, P = .02) and graft weight/body weight ratio ( r = .709, P = .002) showed significant correlations with Tac maintenance doses in the split liver group. Conclusions Peroral Tac bioavailability was significantly higher after partial liver transplantation using the right hepatic lobe compared with full-size transplants. The volume of the split liver graft highly correlated with Tac maintenance therapy and should be used to calculate the most appropriate initial posttransplantation Tac dose.

Multi-organ Early Tumor Dissemination After High Urgency Re-transplantation for Hepatocellular Carcinoma in Cirrhosis: Role of Massive Intraoperative Transfusion?

The recurrence rate of hepatocellular carcinoma (HCC) after liver transplantation (LT) ranges between 11 and 18% [1, 2]. Although the role of post-transplant immunosuppression is still unclear [3, 4], most recurrences seem to be related to malignant cells present but not identified at the time of transplantation and/or released during the transplant procedure. Patients whose explanted liver tumors are within currently accepted criteria for transplantation have a low rate of recurrence [5]. While partial tumor necrosis after performance of bridging treatments could result in earlier tumor recurrence post-transplant [6], 100% tumor necrosis is usually associated with very good results [7]. We report on a patient with unexpected multi-organ early tumor dissemination after an initial LT for a complete necrotic HCC in the setting of cirrhosis and a subsequent high urgency re-transplantation for primary non-function. The patient is a 55-year-old man with chronic hepatitis Binduced liver cirrhosis, Child-Turcotte-Pugh class A, and a solitary recurrent HCC meeting the Milan criteria in Segments VI/VIII. The patient had undergone a partial Segment VII resection in December 2003 for a solitary HCC (pT1 G1 V0). Follow-up examinations proved a local recurrence in Segment VI/VIII in January 2005. Further diagnostic workup (abdominal and thoracic computed tomography, bone scintigraphy, positron emission tomography) excluded further tumor manifestations. The patient was evaluated for LT and listed in ‘‘Eurotransplant’’. A computed tomography (CT)-guided radiofrequency ablation was performed for the 4.8 · 3.4 cm HCC in January 2005. Further follow-up studies with CT, magnetic resonance imaging, and positron emissions tomography (PET)-CT showed complete necrosis of the lesion. After a waiting time of 127 days, the patient received a deceased donor full-size liver graft. The last imaging studies were a magnetic resonance imaging and whole-body PET-CT 2 months prior to LT, showing a necrotic area in the ablated liver segment as well as no further malignancy. Intraoperative mismanagement of inferior vena cava and central venous pressure led to excessive bleeding and corresponding transfusion of 46 units of packed red blood cells, plasma, and coagulation factors. Pathological examination of the explanted liver showed 100% necrosis of the HCC lesion as well as no viable tumor in the setting of end-staged liver cirrhosis. The patient experienced primary graft non-function leading to multiorgan failure, and was re-listed as ‘‘high-urgency’’. Three days later he underwent an uneventful re-LT. Neither of the donors had any history or physical evidence of malignancy. After discharge, the patient was followed up at our outpatient liver transplant clinic. The first HCC imaging follow-up at 4 months post-transplant with abdominal and thoracic CT showed no evidence of HCC recurrence. The second HCC follow-up at 8 months post-transplant showed multifocal bilobar intrahepatic HCC recurrence, intraabdominal involved lymph nodes, and multiple bilateral pulmonary and axillary lymph nodes metastases. Percutaneous liver biopsy confirmed the diagnosis of HCC recurrence. Immunosuppression was switched to rapamycin. The patient opted to receive palliative chemotherapy, fully aware of its limited efficacy, and he died 21 months post-transplant. Although the tumor was a well-differentiated HCC without vascular invasion, radiofrequency ablation resulted G. C. Sotiropoulos (&) S. Beckebaum E. P. Molmenti C. G. Klein V. R. Cicinnati C. E. Broelsch M. Malago Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Hufelandstr. 55, 45122 Essen, Germany e-mail: georgios.sotiropoulos@uni-essen.de

Partial liver transplantation-living donor liver transplantation and split liver transplantation

In the last two decades, liver transplantation (LTx) has become the treatment of choice for several liver diseases including hepatocellular carcinoma in selected cases. Improvements in surgical and anesthesiological procedures have increased patient survival after LTx, resulting in excellent 1-year survival rates. The rate-limiting factor to further increase the number of LTx is the extreme shortage of suitable organs with the consequence that pediatric and adult patients are dying on the waiting list. At present, mortality reported for pediatric and adult patients on the waiting list is 10 to 20%. Living-donor liver transplantation and split liver transplantation are measurements to reduce the severe lack of cadaveric grafts by expanding the donor pool. Major centers around the world now routinely perform partial LTx in infants and adults with survival success equivalent to that after full-size liver transplantation.

Innovative Approaches to Improving Organ Availability for Small Bowel Transplant Candidates

Small bowel transplant candidates have unique features that create special challenges for providing them with organs in a timely manner. More than half of intestinal transplant candidates also need livers. Because there is a greater overall demand for livers than for small bowels, organ allocation in this candidate subset is dictated by the liver allocation policies. However, the extremely high mortality rate associated with patients on the waiting list for combined liver-intestinal transplantation (LIT) attests to the inadequacies of the liver allocation system in recognizing the unique risk factors in patients with intestinal failure who develop end-stage liver disease (ESLD). This report addresses some of the organ allocation issues underlying the discrepancies in waiting list outcomes seen in LIT candidates and discusses possible contributory factors and potential solutions to this problem. The use of living donor and segmental grafts from deceased donors are discussed specifically as potential surgical solutions to the problem, and the potential utility, limitations, and ethical concerns associated with these innovative strategies are discussed.

Analysis of renal function in the immediate postoperative period after partial liver transplantation

Although renal dysfunction is common after liver transplantation, postoperative renal function after split liver transplantation (SLT) has not been well studied. Renal function immediately after surgery was analyzed retrospectively in 16 patients that received a SLT (SLT group). The results were compared with corresponding data from 31 matched patients that received a full-size liver transplant (FSLT group) during the same period. Serum creatinine (SCr) was measured before surgery, and, after transplantation, daily during the first week and at days 14, 21, and 28. Renal dysfunction (RD) was defined as the requirement for renal replacement therapy (RRT) or a 100% increase in SCr if the basal value had been <1.0 mg/dL or a 50% increase in SCr if the basal value had been >1.0 mg/dL. SCr had to be at least 1.5 mg/dL for a diagnosis of RD to be considered. The classification of RD was: mild, SCr 1.5-2.4 mg/dL; moderate, SCr 2.5-4.0 mg/dL; or severe, SCr >4.0 mg/dL (the requirement for RRT). Both donor and recipient age and cold ischemia time were lower in the SLT group than in the FSLT group (P < 0.05). Length of surgery was longer in the SLT group (P < 0.05). There were no significant differences between groups with respect to Model for End-Stage Liver Disease scores, the need for transfusions, the length of admission to the intensive care unit (ICU), survival rate, individual severity index, or sepsis-related organ failure assessment scores at the time of diagnosing RD. Immunosuppression regimens were similar in both groups. RD developed in 82% of SLT patients, but in only 58% of FSLT patients (P = not significant [NS]). Among SLT patients, RD (23.0% mild, 15.5% moderate, and 61.5% severe) was more severe (P = 0.007) than in FSLT patients (63.1% mild, 15.8% moderate, and 24.1% severe). The requirement for RRT in the SLT group (43.7%) was significantly greater (P < 0.05) than that in the FSLT group (12.9%). This finding may be due to the different incidence of sepsis in the 2 groups (SLT 37.5% vs. FSLT 9.7%; P < 0.05). In conclusion, although the number of patients studied was small, our data suggest a higher incidence of RD and a greater requirement for RRT in patients that receive a split liver graft than in those that receive a full size liver graft.

Cadaveric full-size liver transplantation and the graft alternatives in adults: A comparative study from a single centre

This study aims to compare the results of living donor (LDLT), cadaveric split (SLT) and domino (DO) liver transplantation which are currently available alternatives to the conventional cadaveric full-size liver transplantation (CAD). Immunologic, vascular and biliary complications (BC) were evaluated in 38 LDLT, 20 SLT, 17 DO and 38 CAD recipients. The incidence of acute rejection (AR) was similar between groups, and between blood-related and blood-unrelated patients. AR was more severe in the SLT group according to the Banff scores (P=0.03, P<0.001, P<0.001). The evolution of AR was similar between the groups, in terms of development of chronic rejection. No venous complications occurred in the overall population. The rate of arterial thrombosis (10.5, 10, 0 and 3%, respectively) was statistically similar between groups. The rate of BC (26, 40, 12, and 8%, respectively) was higher in the partial grafts than in the whole grafts (P=0.006), but was not significantly different within each group. There was an association between the severity of preservation injury and occurrence of AR (P=0.01) and arterial thrombosis (P=0.016), but not BC. One- and 2-year graft and patient survival rates were similar between groups. None of the graft types seemed to confer immunological advantage. BC remained problematic in the partial grafts, independently from ischemia time.

Detrimental effect of sinusoidal overperfusion after liver resection and partial liver transplantation

Liver resection exposes the remaining sinusoids to an over-proportional blood flow. This mechanism may aggravate ischaemia/reperfusion damage and rejection in partial liver transplants. We studied the potential relevance of this mechanism for the pathogenesis of partial liver transplant dysfunction. Eighty-four isogeneic Lewis rats were divided into four groups: (I) sham operation; (II) partial liver resection (30% residual liver volume); (III) orthotopic transplantation of a full-size liver; (IV) transplantation of a reduced-size liver (30% transplant volume). Microcirculation was determined by intravital microscopy 90 min after surgery. Survival rates, liver function and morphology were monitored over a period of 14 days. Lowest survival rates and impaired liver function were observed after partial liver transplantation (group IV). These transplants displayed the lowest perfusion rate and an increased rate of leukocyte-endothelium interactions in the presence of a significantly increased sinusoidal blood flow velocity compared with those in groups I and III. Sinusoidal overperfusion in groups II and IV resulted in widespread endothelium lesions. Sinusoidal overperfusion seems to be a significant factor impairing liver function after liver resection. In addition to other adverse factors, such as ischaemia/reperfusion injury, it can contribute to the pathogenesis of postoperative dysfunction of partial liver transplants.