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Whilst causes of hepatic artery thrombosis (HAT) after liver transplantation (LT) are multifactorial, early HAT (E-HAT) remains pertinent complication impacting on graft and patient survival. Currently there is no screening tool that would identify patients with increased risk of developing E-HAT.We analyzed the native procoagulant state of LT recipients, identified through pretransplant thromboelastographic (TEG) data among other known risk factors, to identify risk factors for E-HAT.The outcomes of 828 adult patients undergoing LT between 2008 and 2013 were analyzed. Overall, 79 (9.5%) patients experienced HAT, E-HAT was diagnosed in 23, and in the remainder this was "late" HAT. The maximum amplitude (MA) on preoperative TEG was significantly higher in patients diagnosed with E-HAT compared with those who did not (71.2 mm vs 57.9 mm; P0.0001). Receiver operating characteristic analysis with the cutoff value for MA of 65 mm or greater returned area under the curve of 0.750 (P0.001) predicting E-HAT with a sensitivity of 70%. A total of 7% of patients with an MA of 65 mm or greater went on to develop E-HAT (hazard ratio, 5.28; 95% confidence interval, 2.10-12.29; P0.001), whereas only 1.2% patients with an MA less than 65 mm experienced E-HAT.Preoperative TEG may reliably identify group of recipients at greater risk of developing E-HAT, and intense surveillance and anticoagulation prophylaxis may avoid this serious complication after LT.

Left liver grafts have been widely utilized in adult liver transplantation (LT) and yielded acceptable results. However, the conventional orthotopic implantation of a left liver graft imposes the potential risk of perioperative vascular complications. We report herein an alternative modified technique for adult left liver LT and evaluate its feasibility in LT. In this study, 10 recipients had their left liver graft rotated 180°, and heterotopically implanted at the right subphrenic space, which we termed "left at right" liver transplantation (LAR-LT). The sequence of vascular and biliary reconstruction was performed as standard techniques, and no perioperative vascular complications related to LAR-LT were encountered. There were two mortalities in this series, one due to a small-for-size graft dysfunction and the other due to postoperative internal hemorrhage. Two recipients had biliary strictures that were successfully managed by percutaneous biliary dilatation and Roux-en-Y hepaticojejunostomy. The clinical characteristics and outcomes of patients undergoing LAR-LT were also compared with patients undergoing conventional orthotopic left liver LT (n = 14). Although the results showed no significant difference between the two groups, according to our experience, the satisfactory outcome and easier technical reconstruction suggest that the LAR-LT modification could be a feasible alternative to left liver LT.

Background. Dendritic cells (DCs) are crucial regulators of immunity and important in inducing and maintaining tolerance. Here, we investigated the potential of a novel DC-immunomodulating agent, soluble CD83 (sCD83), in inducing transplant tolerance. Methods. We used the C3H-to-C57BL/6 mouse cardiac transplantation model that exhibits a combination of severe cell-mediated rejection and moderate antibody-mediated rejection and investigated whether sCD83 could augment a combination therapy consisting of Rapamycin (Rapa) and anti-CD45RB monoclonal antibody (α-CD45) to prolong allograft survival. Results. Monotherapies consisting of Rapa and α-CD45 were incapable of preventing rejection. However, all treatments involving sCD83 were capable of (1) down-modulating expression of various DC surface molecules, such as major histocompatibility complex class II and costimulatory molecules, (2) reducing the allogeneic stimulatory capacity of the DCs, and (3) significantly inhibiting antidonor antibody responses. Most striking results were observed in the triple therapy-treated group, sCD83+Rapa+α-CD45, where cell-mediated rejection and antibody-mediated rejection were abrogated for over 100 days. Donor-specific tolerance was achieved in long-term surviving recipients, because donor skin transplants were readily accepted for an additional 100 days, whereas third-party skin grafts were rejected. Success of triple therapy treatment was accompanied by enhancement of tolerogenic-DCs that conferred antigen-specific protection on adoptive transfer to recipients of an allogeneic heart graft. Conclusions. Our study revealed that sCD83 is capable of attenuating DC maturation and function, and inducing donor-specific allograft tolerance, in the absence of toxicity. Thus, sCD83 seems to be a safe and valuable counterpart to current DC-modulating agents.

Background and Objectives: Cell therapy provides an effective strategy for the treatment of an impaired liver. Human umbilical cord blood progenitor cells have the potential to differentiate into hepatocytes. Progenitor cells transplanted into the spleen could migrate directly into the liver through portal circulation. To track migration of human umbilical cord blood progenitor cells in cirrhotic rat liver after intrasplenic transplantation and to prove the possibility similar behavior of human umbilical cord blood nucleated cells in humans. Methods and Results: Umbilical cord blood samples from full-term deliveries will be collected after obtaining an informed consent from the mother. The collection procedure will be conducted after completion of delivery and will not interfere with the normal obstetric procedures. Adult male Sprague Dawley rats were subjected to liver cirrhosis by intraperitoneal injection of thioacetamide. Cirrhotic rats were treated with human umbilical cord blood nucleated cells by intra-splenic transplantation. Migration of intrasplenic transplanted human umbilical cord blood cells to the liver was successfully documented with Immunohistochemistry. The liver and spleen from recipient animals were removed. Histopathological and immunohistochemical analysis were performed 20 weeks after intrasplenic injection of the cells. Intrasplenically injected cells migrate to the liver of recipient animals. Conclusions: Human cord blood nucleated cells have the potential to differentiate into hepatocytes and substantially improve the histology and function of the cirrhotic liver in rats. Relocation into liver after intrasplenic transplantation could be detected by immunohistochemistry. Transdifferentiated cells could be efficiently stained with antihuman hepatocytes.

Impact of performing multiple liver transplants (LT) in a short period of time is unknown. Consecutively performed LT potentially increase complication rates through team fatigue and overutilization of resources and increase ischemia time. We analyzed the impact of undertaking consecutive LT (Consecutive liver transplant, CLT; LT preceded by another transplant performed not more than 12 h before, both transplants grouped together) on outcomes. Of 1702 LT performed, 314 (18.4%) were CLT. Outcome data was compared with solitary LT (SLT; not more than one LT in 12-h period). Recipient, donor, and graft characteristics were evenly matched between SLT and CLT; second LT of CLT group utilized younger donors grafts with longer cold ischemic times (P = 0.015). Implantation and operative time were significantly lower in CLT recipients on intergroup analysis (P = 0.0001 and 0.002, respectively). Early hepatic artery thrombosis (E-HAT) was higher in CLT versus SLT (P = 0.038), despite absolute number of E-HAT being low in all groups. Intragroup analysis demonstrated a trend toward more frequent E-HAT in first LT, compared to subsequent transplants; however, difference did not reach statistical significance (P = 0.135). In era of organ scarcity, CLT performed at high-volume center is safe and allows pragmatic utilization of organs, potentially reducing number of discarded grafts and reducing waiting list mortality.

Introduction Acute humoral rejection (AHR), a rare complication in orthotopic liver transplantation (OLT), responds poorly to conventional therapies. Bortezomib, a proteasome inhibitor, has been shown to be effective in treating plasma cell–derived tumors and acute rejection episodes after renal transplantation. Herein, we have reported our clinical experience with bortezomib as a novel approach to treat AHR after OLT. Methods We retrospectively analyzed the 247 adult OLTs performed from January 2007 to April 2011. Patients with AHR who were treated with steroid pulses, rituximab (375 mg/m2), and plasmapheresis (PP) were assigned to group A. Group B subjects were prescribed steroid pulses, rituximab, PP, and bortezomib (1.3 mg/m2), after March 2009. Results Among the 9 patients (3.6%) diagnosed with AHR, all subjects in group A (n = 3) died within several days after AHR, whereas 4/6 (66.7%) group B patients were rescued and 3 (50%) survived at a mean follow-up 22.3 months (range, 18–26). Conclusion Proteasome inhibitor-based therapies provide a more effective strategy to treat AHR after OLT.

Experimental microsurgical procedures in liver research conducted on rat models include liver transplantation, liver resection and portacaval shunt. Transplantation is technically challenging and the first successful rat liver transplant was performed ten years after the first human liver transplant. The rat liver transplantation model has been frequently used for testing organ preservation solutions and Ischemia-reperfusion injury. A subsequently developed partial liver graft transplantation model, used to investigate liver regeneration in combination with portal hypertension, has been used in research supporting the development of live donor liver transplantation. The other relevant interventions described here are portal vein (PV) and/or bile duct ligation.

Refinements of surgical techniques in liver transplant during the last 10 years have offered more successful outcomes for recipients with portal vein thrombosis. Patency of the portal vein after a thrombectomy can be neither adequately evaluated, nor objectively assessed; therefore, we suggest that rerouting part of the portal flow through a "passing loop," with or without augmenting the portal flow, may be a salvage procedure, when there is a possible postoperative rethrombosis of the portal vein.

Liver retransplant is the only treatment for patients with irreversible graft failure. However, given the severe shortage of organs, there is an ethical question of equity in the distribution of this resource. Liver retransplant is more expensive and is associated with lower patient/graft survival rates than equivalent rates after primary transplant. Both primary nonfunction and hepatic artery thrombosis account for nearly all cases of early liver retransplant. Late indications of liver retransplant include chronic rejection, biliary complications, or recurrence of primary disease such as hepatitis C, autoimmune hepatitis, and primary sclerosing cholangitis. Donor data are not available when a patient is listed for liver retransplant; therefore, prognostic factors related to the recipient is a more practical way of making the decision to offer liver retransplant is made. In the Model of End-stage Liver Disease era liver retransplant for "late" indications is more complex and selection criteria are more stringent. We review the literature for predictive factors influencing outcome of liver retransplant, especially in those with recurrent disease.

Due to lack of tactile feedback, available retractors might inadvertently cause traumatic injury to the liver, leading to unnecessary bleeding, especially in patients with bleeding diathesis. Hand-assisted retraction might also be less than ideal, either due to wrist fatigue leading to frequent change in magnitude and direction of traction, fear of undue tension on draining veins, fear of subcapsular tumor rupture, or simply due to slippery liver capsule. We devised a simple trick using a piece of gauze for safer mobilization of the right lobe; especially those bearing large subcapsular tumors. This maneuver offers better caval exposure, less IVC compression, less twisting on hilar pedicle, and less pressure on tumor-bearing hepatic parenchyma, thus, decreasing incidence of dissemination. Favorable results were obtained when this technique was applied on the large right lobes with long anteroposterior diameter and convex lateral surface like those bearing subcapsular tumors; however, no advantage was found in small firm cirrhotic liver. This technique allows adequate and prolonged surgical exposure with minimal wrist strain with flexible change of position allowing readjustment in either the tensile force or in the vector direction; however, impact on hemodynamics needs further assessment.

Background The modified piggyback technique with side-to-side cavocavostomy decreases the risk of outflow obstruction compared with the standard piggyback method. However, this modification is not ideal for recipients who receive a graft that is voluminous or bears an enlarged caudate lobe. Methods We modified the inferior vena cava (IVC) preservation technique against deleterious complications of compression by using a passing loop. Case Presentation A 49-year-old woman, who underwent orthotopic liver transplantation for hepatic failure, was allocated a large-size liver. In anticipation of serious caval compression due to the voluminous grafts, we kept the suprahepatic or infrahepatic donor caval cuffs open for an anastomosis. The first anastomosis was performed between suprahepatic donor IVC cuff and recipient middle-left hepatic vein common channel; the second anastomosis was a terminolateral cavocavostomy between infrahepatic donor IVC cuff and the anterior wall of the recipient's IVC. Discussion When the liver circulation was restored, the donor retrohepatic vena cava served as a passing loop for both hepatic venous outflow and infra-diaphragmatic venous return to bypass possible IVC compression. Our technique may solve a dilemna for patients receiving voluminous liver grafts.

Biliary reconstruction has been described 35 years ago by Sir Roy Calne as the technical ‘Achilles heel’ of orthotopic liver transplantation (OLT). The name “Achilles' heel” comes from Greek mythology, which is a metaphor of a single vulnerable spot. This is because the potential detrimental effects of biliary complications on graft and patient survival. Biliary complications, which “plagued” the early experience of liver transplantation occurring in nearly one of every three transplant recipients (Moser & Wall, 2001), have been reduced dramatically due to the improvements in organ selection, retrieval, preservation, and implantation techniques. However, biliary complications still remain a common source of morbidity and mortality (Greif et al., 1994). Additionally, they significantly affect the recipients’ quality of life because they entail frequent readmissions, repeated imaging, invasive procedures, and even reoperation. All of them added to the financial and emotional toll suffer the patients (Sharma et al., 2008). Biliary leaks and strictures, either anastomotic or non-anastomotic, are the most frequent complications. Cystic duct obstruction due to mucocele, stones, sludge or casts, hemobilia and sphincter of Oddi dysfunction have also been recorded (Colonna et al., 1992; Greif et al., 1994). The surgical management used to be the standard of care for these conditions in earlier practice. However, the revolutionary progress in minimally invasive armamentarium, namely endoscopy and percutaneous radiologic interventional modalities, made it the current alternative first line of management displacing surgical intervention to be a second backup option (Sharma et al., 2008; Williams & Draganov, 2009). A living donor liver transplantation (LDLT) was first reported in 1988 by Raia in Brazil, followed by Nagasue in Japan in 1989. After the leading successful experience of right lobe living related liver transplantation (RL-LDLT) that has been reported by Hong Kong team in 1996, it rapidly evolved as a well-established practice in Asian countries. World wide organ shortage and promising results were alluring to other centers to consider (RL-LDLT) as a practical option. In this review we will shed more light on biliary complications related to right lobe living donor liver transplantation and their endoscopic management.

Surgical resection remains the first line of treatment for earlier stages of hepatocellular carcinoma (HCC), and it offers the best prognosis for long-term survival. Nevertheless, the recurrence rates after resection are still high in reports. Therefore, it is still essential to explore any potential prognostic factors to attain relatively longer-term survival of HCC patients.In the period from 1983 to 2005, 1,685 patients who underwent hepatectomy at Chang Gung Memorial hospital were enrolled in the study, and their clinicopathological data were retrospectively reviewed for survival analysis.The 1-, 3-, 5-, and 10-year disease-free survival (DFS) rates in this series were 60.3%, 39.7%, 31.3%, and 24.0%, respectively, whereas the 1-, 3-, 5-, and 10-year overall survival (OS) rates were 80.1%, 59.1%, 46.6%, and 27.7%, respectively. Gross vascular invasion, tumor status, lymph node involvement, satellite lesion, positive surgical margin, alkaline phosphatase (ALP), albumin, presence of cirrhosis, and Child grade B or C were independent prognostic factors for prediction of DFS; while α-fetoprotein, ALP, surgical factors, including complications, blood transfusion, positive resection margin, and tumor characters including tumor status, vascular invasion, and lack of tumor encapsulation were found to be independent predicting factors for OS, as determined by Cox regression analysis. Interestingly, we found that preoperative level of ALP was one of the most important independent predictors of recurrence, even more important that α-fetoprotein (AFP) as we noticed that elevation of ALP above (82 U/L) predicted poor prognosis in patients where AFP levels was less than 66 ng/ml. It is worth to mention that ALP was statistically related to other liver function tests, but not tumor characters by hierarchical clustering; which means that we were able to correlate ALP with prognosis statistically, but not with pathological criteria of the tumor; to elucidate these finding, further basic science research is required.ALP among liver function tests, in addition to other tumor characters were independent factors for DFS and OS; our results suggest that preoperative ALP levels could be utilized to monitor and predict recurrence in high risk HCC patients.

The discovery of the pluripotent stem cells made the prospect of cell therapy and tissue regeneration a clinical reality, especially with the evidence of contribution of the stem cells of bone marrow origin in hepatic regeneration. Infusion of bone marrow stem cells before trans-arterial chemoembolization may help to increase liver volume and consequently increase hepatic reserve in patients with HCC, and this may improve the outcome of this procedure.Four Child B class patients with unresectable hepatocellular carcinoma treated by transarterial chemoembolization were injected with autologous bone marrow mononuclear layer containing stem cell in the hepatic artery feeding the contralateral lobe of the liver in the same session, follow-up of the patients was done by doing liver profile and CT liver volumetry before the surgery and 3 months later.We observed that patients receiving stem cell therapy simultaneously with TACE had shown a significant improvement in biological and volumetric parameters of liver function compared to those historically reported of patients receiving TACE only who usually shows deterioration of liver parameters.BMC infusion into the hepatic artery synchronized with TACE for patients with chronic liver disease complicated with HCC is safe, feasible, and demonstrated an improvement in both biological and radiological volumetric parameters.

Overweight/obesity is currently a common health issue that may cause many diseases, even malignancies. The influence of steatosis on long-term results of surgical treatment for hepatocellular carcinoma (HCC) is not well known. The aim of this study is to analyze the results of hepatectomy for HCC patients with steatosis.The study included 1048 patients who underwent hepatectomy for HCC from 1999 to 2005. The patients were divided into two groups; group A patients without steatosis (n = 693) and group B patients with steatosis (n = 355). The clinicopathological data and long-term survival were analyzed.Mean tumor size in group B patients was smaller than that in group A patients (4.61 ± 3.40 vs. 5.91 ± 4.36 cm, p0.01). Group B patients showed lower tumor differentiation grade, lower vascular invasion rate and better 5-year overall survival compared to group A patients (61.2% vs. 50.1%, p = 0.001). By multivariate analysis, steatosis was found to be associated with well-differentiated, small-sized, and less α-fetoprotein productive tumors. When focusing on the tumors5 cm in diameter, group B patients had better survival rate than group A patients (p = 0.041). Vascular invasion and steatosis were independent prognostic factors for the overall survival.HCC in steatotic liver was less aggressive than that in non-steatotic liver. HCC patients with steatosis have better surgical outcomes than those without steatosis. Vascular invasion and steatosis were independent prognostic factors for the overall survival if tumors were5 cm in diameter.