Full-size Orthotopic Liver Transplantation Research Articles

Hepaticojejunostomy in Orthotopic Liver Transplant: A Retrospective Case Control Study

The reported biliary morbidity rate for deceased donor full-size orthotopic liver transplantation is up to 30%. The technique used may be influenced by multiple factors, and in some situations, biliary reconstruction must be carried out through Roux-en-Y hepaticojejunostomy. The aim of our study was to determine the results of the orthotopic liver transplantation according to the technique used in the biliary reconstruction. A retrospective study was performed with the first 1000 orthotopic liver transplants (951 patients) carried out consecutively (1996-2013) with follow-up until 2017. A matched case-control study was designed in 1:3 ratio (47/136) to compare the reconstruction by hepaticojejunostomy vs the end-to-end coledoco-coledocostomy. Hepaticojejunostomy was associated with patients with cholestatic (44.7% vs 3.7%) and ischemic disease (14.9% vs 0%; P < .001) and previous transplant (29.8% vs 1.5%; P = .003). The mean biliary duct reconstruction, surgery, and cold ischemia times were also higher. Vascular complications were significantly more frequent in the hepaticojejunostomy group (36.1% vs 10.4%; P < .001), mainly because of differences in early arterial complications. Nevertheless, there were no differences in the total biliary complication (21.2% vs 16.9%; P = .5). The biliary leakage rate and the biliary stricture rate were also similar. Hepaticojejunostomy in orthotopic liver transplantation presented longer biliary reconstruction, surgery, and cold ischemia times when compared with end-to-end coledoco-coledocostomy. In addition, it was followed by a higher incidence of arterial complications but had similar biliary complication rate and graft survival. Differences could be explained by the fact that hepaticojejunostomy was used more often in cholestatic or ischemic diseases and in retransplant procedures.

Suppression of Graft Regeneration, Not Ischemia/Reperfusion Injury, Is the Primary Cause of Small-for-Size Syndrome after Partial Liver Transplantation in Mice

BackgroundIschemia/reperfusion injury (IRI) is commonly considered to play a crucial role in the pathogenesis of small-for-size syndrome (SFSS) after liver transplantation. Rapid regeneration is also considered essential for the survival of SFS grafts.MethodsMouse models of full-size orthotopic liver transplantation, 50% partial liver transplantation and 30% partial liver transplantation were established. Survival rate and serum alanine aminotransferase were observed. IRI was assessed by hepatic pathologic alterations, apoptosis and necrosis. Regeneration response was detected by mitotic index, BrdU incorporation and PCNA, Cyclin D1 and Cyclin E expression. The expression of mTOR, AKT, ERK, JNK2 and p70S6K, also involved in regeneration signaling pathways, were analyzed as well.Results30% partial liver graft resulted in a significantly low 7-day survival rate (P = 0.002) with no marked difference in tissue injury compared with the 50% partial graft group. Serum alanine aminotransferase levels were not significantly different between partial transplantation and full-size transplantation. Western blot analysis of caspase-3 and TUNEL staining also indicated no significant difference in apoptosis response between 30% partial transplantation and half-size or full-size transplantation (P = 0.436, P = 0.113, respectively). However, liver regeneration response indicators, mitotic index (P<0.0001) and BrdU (P = 0.0022), were markedly lower in 30% LTx compared with 50% LTx. Suppressed expression of PCNA, cyclin D1, cyclin E, mTOR, JNK2, AKT, ERK and p70S6K was also detected by western blot.ConclusionsLiver regeneration is markedly suppressed in SFSS, and is more likely the primary cause of SFSS, rather than ischemia/reperfusion injury. Therapy for recovering graft regeneration could be a potentially important strategy to reduce the incidence of SFSS.

Suppression of liver regeneration affects hepatic graft survival in small‐for‐size liver transplantation in rats

Small-for-size liver transplantation (SFSLT) often results in hepatic graft failure and decreased survival. The present study was aimed to investigate the possible mechanism of hepatic graft failure in SFSLT in rats. Rat models of full-size orthotopic liver transplantation, 50% partial liver transplantation and 30% partial liver transplantation were established. Proliferative responses of the hepatic graft were evaluated by immunohistochemical staining and western blotting. Apoptosis-, inflammatory-, anti-inflammatory- and growth factor-related genes were screened by quantitative reverse transcription polymerase chain reaction. Activities of transcription factors of AP-1 and nuclear factor (NF)-κB were analyzed by electrophoretic mobility shift assay. A 30% partial liver transplant not only resulted in marked structural damages to the hepatic graft, but also showed the lowest 7-day survival rate. In addition, sup pressed expressions of proliferating cell nuclear antigen (PCNA) and cyclin D1 by immunohistochemical staining and decreased expressions of cyclin D1 and p-c-Jun by western blotting were detected. Downregulated expressions of Bcl-2, Bcl-XL, interleukin (IL)-6, IL-10, IP-10 and CXCR2, upregulated expression of tumor necrosis factor-α, and decreased levels of AP-1 and NF-κB were also found following 30% partial liver transplantation after reperfusion. Liver regeneration is remarkably suppressed in SFSLT. The significant changes of intra-graft gene expression described above indicated that ischemia reperfusion injury would be severe in 30% partial liver transplantation. The capability of liver regeneration secondary to ischemia reperfusion injury might determine hepatic graft survival in SFSLT.

Similar liver transplantation survival with selected cardiac death donors and brain death donors

The outcome of orthotopic liver transplantation (OLT) with controlled graft donation after cardiac death (DCD) is usually inferior to that with graft donation after brain death (DBD). This study compared outcomes from OLT with DBD versus controlled DCD donors with predefined restrictive acceptance criteria. All adult recipients in the Netherlands in 2001-2006 with full-size OLT from DCD (n = 55) and DBD (n = 471) donors were included. Kaplan-Meier, log rank and Cox regression analyses were used. One- and 3-year patient survival rates were similar for DCD (85 and 80 per cent) and DBD (86.3 and 80.8 per cent) transplants (P = 0.763), as were graft survival rates (74 and 68 per cent versus 80.4 and 74.5 per cent; P = 0.212). The 3-year cumulative percentage of surviving grafts developing non-anastomotic biliary strictures was 31 per cent after DCD and 9.7 per cent after DBD transplantation (P < 0.001). The retransplantation rate was similar overall (P = 0.081), but that for biliary stricture was higher in the DCD group (P < 0.001). Risk factors for 1-year graft loss after DBD OLT were transplant centre, recipient warm ischaemia time and donor with severe head trauma. After DCD OLT they were transplant centre, donor warm ischaemia time and cold ischaemia time. DCD graft was a risk factor for non-anastomotic biliary stricture. OLT using controlled DCD grafts and restrictive criteria can result in patient and graft survival rates similar to those of DBD OLT, despite a higher risk of biliary stricture.

Orthotope Lebertransplantation

Since 1963, orthotopic liver transplantation (OLT) has developed into an established interdisciplinary therapy concept for patients with end-stage liver disease, acute irreversible liver failure, and hepatic malignancies in selected cases. In 26 centers in Germany, around 900 full-size OLTs are performed annually. The classic technique has been replaced by the "piggyback" method, which has become the standard in many centres. Improvements in surgical techniques, anaesthetic protocols, and medical management along with the introduction of new immunosuppressive regimens and early adequate therapy against infections and transplant rejection have increased patient survival. These factors have resulted in 1-year survival rates of 80-90% and led to an increase in indications for OLT. Despite decades of experience, approximately 10% of the mortality in the first 3 months still can be traced to technical complications.

Split-liver transplantation: One plus one doesn’t always equal two

Surgical reduction of donor livers to treat small children has been performed successfully in several centers. While this procedure improves the allocation of livers, it does not increase the organ supply. We have extended reduced-size orthotopic liver transplantation (OLT) to treat 18 patients with 9 livers, accounting for 26% of our transplants during a 10-month period and have evaluated the results. In 18 split liver OLTs, patient survival was 67% and graft survival was 50%. In comparison, for 34 patients treated with full-size OLT during the same period, patient survival was 84% (p = 0.298) and graft survival was 76% (p = 0.126). Biliary complications were significantly more frequent in split grafts, occurring in 27%, as compared to 4% in full-sized grafts (p = 0.017). Primary nonfunction (4% versus 5.5%) and arterial thrombosis (6% versus 9%) occurred with similar frequency in split and full-size OLT (p = not significant). These results demonstrated that split-liver OLT is feasible and could have a substantial impact in transplant practice. We believe that biliary complications can be prevented by technical improvements and that split-liver OLT will improve transplant therapy by making more livers available. The University of Chicago program in pediatric liver transplantation continues actively to seek innovative surgical solutions to problems related to the management of children with end-stage liver disease. Among the most important problems facing these children is a shortage of donor organs, which results from three factors in addition to the actual supply of pediatric donors: the concentration of pediatric liver disease in the population younger than 2 years; the necessity for a graft that is small enough; and the epidemiology of accidents and other events that lead to organ donation. Transplantation using a liver love as a graft overcomes size disparity and shifts the available supply of organs fromolder donors to tounger recipients. This work describes the technical aspects of recent innovations in the use of liver lobes in pediatric transplantation, simple reduced-size liver transplantation (RLT), split-liver transplantation (SLT), orthotopic auxiliary liver grafting (ALT), and transplantation using a living related donor (LRLT), and compares their results. Since November 1986 a total of 61 procedures have been performed in which a liver lobe was used as a graft: 26 RLT;30 SLT,25 in children and 5 in adults; 5 LRLT; and 1 ALT. Overall 62% of transplants performed in children have involved using a liver lobe as a graft. The rates of ccomplications are somewhat higher than with whole-liver transplantation, but this may not be entirely the result of the complex procedures. Split liver transplantation is associated with complications in donors and recipients, but to date survival is 100%. Orthotopic auxillary liver transplatation effectively corrected the metabolic defect n one patient with ornithine transcarbamylase deficiency. Overall the various modalities of using graft reduction have reduction have resulted in postoperative results similar to those aachieved with full-size grafts, while pretransplantation mortality has been limited to less than 2%. Thous the use of grafts as liver lobes accomplisshes the goal of reducing global mortality among children with end-stage liver disease, but at the cost of increased surgical complexity and more postoperative complications.

The Use of Reduced-Size Liver Transplants in Children, Including Split Livers and Living Related Liver Transplants

One of the key problems facing children awaiting liver transplantation is the shortage of donor organs. Surgical procedures that address this problem include: reduced-size liver transplantation (RLT), split liver transplantation (SLT), and living related liver transplantation (LRLT). RLT makes more of the current donor pool accessible to the pediatric recipient. SLT furnishes 2 liver grafts from 1 cadaveric donor, and LRLT provides an innovative supply of donor organs. This report compares the results achieved with RLT, SLT, and LRLT to those seen with full-size orthotopic liver transplantation (OLT). Between November 1984 and February 1991, 457 liver transplants were performed at the University of Chicago. Two hundred fourteen of these transplants were placed into recipients less than 13 years of age. Of these 214 pediatric orthotopic liver transplants (OLT), 103 were full-size livers and 111 were some type of reduced graft (RLT, SLT, or LRLT). There were 57 RLT, 34 SLT, and 20 LRLT. The recipients of the reduced grafts (RLT, SLT, or LRLT) averaged 1.9 +/- 1.8 years of age and 9.6 +/- 6.4 kg compared to the recipients of the full-size livers who averaged 3.5 +/- 3.4 years of age and 14.1 +/- 8.8 kg (p = 0.0001). The most common indication for transplantation was biliary atresia (105 patients). Overall patient survival after primary full-size OLT was 71.8%. Reduced-size OLT (RLT, SLT, and LRLT) resulted in an overall patient survival of 72.6% after primary transplantation. Patient survivals for primary transplants with specific types of reduced-size grafts were: RLT 76.5% (after RLT was used routinely), SLT 66.7%, and LRLT 89.5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Transplantation of Two Patients with One Liver

Surgical reduction of donor livers to treat small children has been performed successfully in several centers. While this procedure improves the allocation of livers, it does not increase the organ supply. We have extended reduced-size orthotopic liver transplantation (OLT) to treat 18 patients with 9 livers, accounting for 26% of our transplants during a 10-month period and have evaluated the results. In 18 split liver OLTs, patient survival was 67% and graft survival was 50%. In comparison, for 34 patients treated with full-size OLT during the same period, patient survival was 84% (p = 0.298) and graft survival was 76% (p = 0.126). Biliary complications were significantly more frequent in split grafts, occurring in 27%, as compared to 4% in full-sized grafts (p = 0.017). Primary nonfunction (4% versus 5.5%) and arterial thrombosis (6% versus 9%) occurred with similar frequency in split and full-size OLT (p = not significant). These results demonstrated that split-liver OLT is feasible and could have a substantial impact in transplant practice. We believe that biliary complications can be prevented by technical improvements and that split-liver OLT will improve transplant therapy by making more livers available.

Reduced-size orthotopic liver transplantation: use in the management of children with chronic liver disease.

Reducing the size of a liver for use in a recipient smaller than the donor is one way to reduce mortality before orthotopic liver transplantation in children because of the scarcity of pediatric organ donors. In this report, we review the results of this approach over the past 2 years, during which we have used reduced-size orthotopic liver transplantation routinely in small children. Forty-nine children underwent orthotopic liver transplantation between September, 1986, and October, 1988; orthotopic liver transplantation with a whole organ (full-size orthotopic liver transplantation) was performed in 36 children, whereas 13 patients received reduced-size orthotopic liver transplantation. In two pairs of patients, the reduced grafts were obtained from single donors, using a "split-liver" procedure. All grafts were implanted in the orthotopic position following total recipient hepatectomy. The preoperative diagnostic categories were not significantly different between groups. Patients receiving reduced-size orthotopic liver transplantation were younger (1.6 +/- 1.5 vs. 4.4 +/- 4.6 years), and a higher percentage were in the intensive care unit prior to transplant (31 vs. 9%). Thirty of 36 (82%) patients receiving full-size orthotopic liver transplantation and 10 of 13 (77%) patients receiving reduced-size orthotopic liver transplantation are alive 3 to 27 months after transplantation. The rates of retransplantation were 24% for full-size orthotopic liver transplantation and 15% for reduced-size orthotopic liver transplantation. Despite the greater complexity of reduced-size orthotopic liver transplantation and the higher frequency of critically ill recipients selected for the procedure, the results of reduced-size orthotopic liver transplantation are comparable with full-size orthotopic liver transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)