Living-related liver transplantation (LRLT) was developed to increase the donor pool of size-matched organs for children. In the UK only one centre performed LRLT between 1993 and 2008. This study reports the clinical and histological outcomes following adult-to-paediatric LRLT at our centre.

Forty-six LRLTs were reviewed. Recipients had a mean age, weight and PELD score of 2.4years (range 0.5-11years), 11.0kg (3.7-32.3kg) and 11.7 (-20.3 to 49.1) respectively. The incidence of post-transplant paediatric morbidity, abnormal liver function tests and histological abnormalities was reviewed.

Patient and graft survival rates were 97.8%, 95.1% and 95.1%, and 97.8%, 92.1% and 71.7% at 1, 5 and 10years post-transplant respectively. Three children were re-transplanted at 44, 100 and 119months post-transplant. Nine children developed neuropsychological problems, 6 experienced educational difficulties, 5 developed post-transplant lymphoproliferative disorder and 5 suffered height or weight growth<2 centile. Normal LFTs were found in 41.7%, 50%, 68% and 64.7% of children at median follow-up of 6, 13, 61 and 85months respectively. Liver histology showed hepatitis, acute rejection, non-specific changes, biliary pathology, vascular pathology and chronic rejection in 32.9%, 29.5%, 13.4%, 10.1%, 6% and 2% of biopsies respectively.

The prevalence of paediatric morbidity and histological abnormalities emphasize the need for specialist and long-term follow-up following LRLT in children.

Little data concerning hospital charges and long-term outcomes of LDLT in North American children according to transplant indications have been published. To compare outcomes of patient and graft survival and healthcare charges for LDLT for those with BA vs. other diagnoses (non-BA). A retrospective review of 52 children receiving 53 LDLT (38 BA and 14 non-BA) from 1992 to 2010 at our institution was performed. One-, five-, and 10-yr patient and graft survival data were comparable to national figures reported to UNOS. Average one-yr charges for recipients and donors were $242 849 for BA patients and $183 614 for non-BA (p = 0.074). BA patients were 1.23 ± 1.20 yr of age vs. 4.25 ± 5.02 for non-BA, p = 0.045. Examination of the total population of patients who were alive in 2010 in five chronological groupings showed that the crude five-yr survival rates were 1992-1995: 9/11 (82%); 1995-1997: 6/10 (60%); 1997-1999: 8/10 (80%); 1999-2001: 9/10 (90%); and 2001-2003: 7/7 (100%). Thus, examination of the clinical and financial data together over the entire period of the transplant program suggests that the dramatic improvement in patient survival was accomplished without a dramatic increase in indexed charges. All 53 donors survived, and only 10% had complications requiring hospitalization. LDLT in children results in excellent outcomes for patients and donors. Ways to lower costs and maximize graft outcome should be investigated.

We recently developed a novel rat model for liver repopulation, heterografting of microliver slices, aimed at overcoming the limitations inherent in both whole liver and hepatocyte transplantations. The aim of the present study was to evaluate the potential of whole fetal liver transplantations to survive and differentiate within the adult liver, using the adult liver slice transplantation model. Embryonic day 14 whole fetal livers from dipeptidyl peptidase IV+/+ wild-type Fischer 344 rats were transplanted into the livers of dipeptidyl peptidase IV-/- mutant rats. Adult hepatic markers, dipeptidyl peptidase IV, albumin, glycogen, and proliferation cell nuclear antigen- proliferation cell nuclear antigen (PCNA) were assessed in the transplanted liver tissue by immunohistochemistry. Two groups of 9 rats each were transplanted with 3 fetal livers per recipient. Two months later the rats were sacrificed and the markers were detected in the transplanted tissues. In conclusion, the results of this study raise the possibility that fetal liver transplantation could serve as a model for genetic metabolic liver diseases.

The technique of liver splitting offers an effective way of increasing the donor pool and decreasing pediatric waiting list mortality. A donor liver is divided in such a way that the left lateral liver graft can be transplanted into a small child and the right extended liver graft into an adult. This innovative technique did not harm the adult recipient pool. Because of its technical complexity and the initial poor results after split liver transplantation (SLT) this procedure has slowly gained acceptance in the Transplantation Community after its first introduction in 1988 (4). Small children with end stage liver disease suffered the most from the extreme shortage of cadaveric donor organs due to the difficulty of finding size-matched donors. The successful surgical development of SLT and a better donor and recipient selection have led to a reduction of the pediatric pretransplant mortality to nearly zero and to results comparable with those after whole organ transplantation (WLT). By splitting a donor organ into two 'full' hemi-grafts and providing a small adult ( < 60 kg) or a big child ( > 30 kg) with the full left graft and a medium-sized adult (60-80 kg) with the full right graft, a small-for-size situation for adolescents or adults can be avoided and the total number of available grafts can be increased. It is the goal to provide each recipient with its customized graft in the near future. However, splitting for two adults requires high technical skills and profound knowledge of the anatomic variations and should be performed in centers with large transplantation experience.

Various stem cell populations have been described in distinct models of liver regeneration. This review provides an overview of these different stem cell populations aimed at unifying diverse views of liver stem cell biology. Embryonic stem cells, hemopoietic stem cells, mesenchymal stem cells, liver-derived hepatic stem cells, bone marrow-derived hepatic stem cells, and mature hepatocytes (as cells with stemlike properties) are considered separately. In so doing, we seek to clarify the nomenclature of putative liver stem cell types. Experiments that address the question of cellular fusion versus transdifferentiation as explanations for observed liver regeneration are highlighted. This review concludes with a series of open questions that should be addressed in the context of clinical liver disease before attempts at human therapeutic interventions.

The progressive shortage of liver donors has mandated investigation of living-donor transplantation (LDT). Concerns about increasing risk to the donor are evident, but the impact of the degree of parenchymal loss has not been quantified. We analyzed clinical and biological variables in 45 LDT performed by our team over 2years to assess risks faced in adult LDT. All donors are alive and well with complete follow-up through to February 2001. When the three operations were compared, right hepatectomy (RH) was significantly longer in terms of anesthesia time and blood loss compared with left hepatectomy (LH) and left lobectomy (LL). Donor remnant liver was significantly reduced after RH compared with LH and LL. There were significant functional differences as a consequence of the remnant size, measured by an increase in peak prothrombin time after RH. RH for adults represents a markedly different insult from pediatric donations in terms of parenchymal loss and early functional impairment. Left hepatectomy donation offers modest advantage over right lobes but seems to confer substantial technical risk for a small gain in graft size. Unless novel strategies are developed to enhance liver function of the LH graft in the adult recipient, right lobe donation will be necessary for adult LDT.

This paper provides a review of the practice of liver transplantation with the main emphasis on UK practice and indications for transplantation.

This section reviews the process of referral and assessment of patients with liver disease with reference to UK practice.

The practice of brainstem death and cadaveric organ donation is peculiar to individual countries and rates of donation and potential areas of improvement are addressed.

The technical innovations that have led to liver transplantation becoming a semi-elective procedure are reviewed. Specific emphasis is made to the role of liver reduction and splitting and living related liver transplantation and how this impacts on UK practice are reviewed. The complications of liver transplan-tation are also reviewed with reference to our own unit. Immunosuppression:The evolution of immunosuppression and its impact on liver transplantation are reviewed with some reference to future protocols.

The role of retransplantation is reviewed.

The results of liver transplantation are reviewed with specific emphasis on our own experience.

The future of liver transplantation is addressed.

The systematic application of living-related and cadaveric, in situ split-liver transplantation has helped to alleviate the critical shortage of suitable-sized, pediatric donors. Undoubtedly, both techniques are beneficial and advantageous; however, the superiority of either graft source has not been demonstrated directly. Because of the potential living-donor risks, we reserve the living donor as the last graft option for pediatric recipients awaiting liver transplantation. Inasmuch as no direct comparison between these two graft types has been performed, we sought to perform a comparative analysis of the functional outcomes of left lateral segmental grafts procured from these donor sources to determine whether differences do exist.

A retrospective analysis of all liver transplants performed at a single institution between February 1984 and January 1999 was undertaken. Only pediatric (<18 years) recipients of left lateral segmental grafts procured from either living-related (LRD) or cadaveric, in situ split-liver (SLD) donors were included. A detailed analysis of preoperative, intraoperative, and postoperative variables was undertaken. Survival was estimated using the Kaplan-Meier method, and comparison of variables between groups was undertaken using the t test of Wilcoxon rank sum test.

There were no significant differences in the preoperative variables between the 39 recipients of SLD grafts and 34 recipients of LRD grafts. The donors did differ significantly in mean age, ABO blood group matching, and preoperative liver function testing. Postoperative liver function testing revealed significant early differences in aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, prothrombin time, and alkaline phosphatase, with grafts from LRD performing better than those from SLD. SLD grafts also had significantly longer ischemia times and a higher incidence of graft loss owing to primary nonfunction and technical complications (9 vs. 2, P<0.05). However, six of these graft losses in the SLD group were because of technical or immunologic causes, which, theoretically, should not differ between the two groups. Furthermore, these graft losses did not negatively impact early patient survival as most patients were successfully rescued with retransplantation (30-day actuarial survival, 97.1% SLD vs. 94.1% LRD, P=0.745). In the surviving grafts, the early differences in liver function variables normalized.

Inherent differences in both donor sources exist and account for differences seen in preoperative and intraoperative variables. Segmental grafts from LRD clearly performed better in the first week after transplantation as demonstrated by lower liver function variables and less graft loss to primary nonfunction. However, the intermediate function (7-30 days) of both grafts did not differ, and the early graft losses did not translate into patient death. Although minimal living-donor morbidity was seen in this series, the use of this donor type still carries a finite risk. We therefore will continue to use SLD as the primary graft source for pediatric patients awaiting liver transplantation.

To assess and compare the value of split-liver transplantation (SLT) and living-related liver transplantation (LRT).

The concept of SLT results from the development of reduced-size transplantation. A further development of SLT, the in situ split technique, is derived from LRT, which itself marks the optimized outcome in terms of postoperative graft function and survival. The combination of SLT and LRT has abolished deaths on the waiting list, thus raising the question whether living donor liver transplantation is still necessary.

Outcomes and postoperative liver function of 43 primary LRT patients were compared with those of 49 primary SLT patients (14 ex situ, 35 in situ) with known graft weight performed between April 1996 and December 2000. Survival rates were analyzed using the Kaplan-Meier method.

After a median follow-up of 35 months, actual patient survival rates were 82% in the SLT group and 88% in the LRT group. Actual graft survival rates were 76% and 81%, respectively. The incidence of primary nonfunction was 12% in the SLT group and 2.3% in the LRT group. Liver function parameters (prothrombin time, factor V, bilirubin clearance) and surgical complication rates did not differ significantly. In the SLT group, mean cold ischemic time was longer than in the LRT group. Serum values of alanine aminotransferase during the first postoperative week were significantly higher in the SLT group. In the LRT group, there were more grafts with signs of fatty degeneration than in the SLT group.

The short- and long-term outcomes after LRT and SLT did not differ significantly. To avoid the risk for the donor in LRT, SLT represents the first-line therapy in pediatric liver transplantation in countries where cadaveric organs are available. LRT provides a solution for urgent cases in which a cadaveric graft cannot be found in time or if the choice of the optimal time point for transplantation is vital.

This paper provides a review of the practice of liver transplantation with the main emphasis on UK practice and indications for transplantation.

This section reviews the process of referral and assessment of patients with liver disease with reference to UK practice.

The practice of brainstem death and cadaveric organ donation is peculiar to individual countries and rates of donation and potential areas of improvement are addressed.

The technical innovations that have led to liver transplantation becoming a semi-elective procedure are reviewed. Specific emphasis is made to the role of liver reduction and splitting and living related liver transplantation and how this impacts on UK practice are reviewed. The complications of liver transplan-tation are also reviewed with reference to our own unit. Immunosuppression:The evolution of immunosuppression and its impact on liver transplantation are reviewed with some reference to future protocols.

The role of retransplantation is reviewed.

The results of liver transplantation are reviewed with specific emphasis on our own experience.

The future of liver transplantation is addressed.

The outcome of fulminant hepatic failure without timely liver transplantation is poor. We describe a 19-year-old woman with fulminant hepatic failure due to acute hepatitis B infection who received a living donor liver transplant from her sister. The donor's recovery was uneventful, allowing hospital discharge on Day 6. Two months after transplantation the recipient developed a biliary stricture requiring surgery. One year after transplantation, her liver function was normal.