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This chapter summarizes analyses of 51,060 adult primary liver-only transplants from deceased donors reported to the OPTN/UNOS Liver Transplant Registry from 1995 to 2009. Despite advances in surgical techniques and immunosuppression, analysis shows improvement in one-year graft but no improvement in long-term graft survival. Adoption of the Model for End-Stage Liver Disease (MELD) score for organ allocation--prioritizing sicker patients for transplantation--has significantly influenced liver transplant procedures. Accordingly, we classified the transplants into two groups: 1995-2001 (pre-MELD era) and 2002-2007 (MELD era), and our analyses found that long-term survival of liver grafts remained almost unchanged between the two eras. Patient pre-transplant status was better in the MELD era. But when we analyzed the grafts that survived more than one year, survival rates were slightly better pre-MELD than in the MELD era (82.2% and 80.34%, respectively) and risk of graft failure was slightly higher in the MELD era. This chapter also provides analyses of current graft survival rates for 10 different primary liver diseases. Hepatocellular carcinoma, hepatitis C virus cirrhosis, and alcoholic liver disease account for almost 50 % of the primary diseases, and have worse graft survival than the other primary diseases. The lack of improvement in long-term survival suggests an on-going need for means to avoid chronic liver graft dysfunction and to develop therapeutic interventions to control chronic graft loss.

Based on the data reported to the OPTN/UNOS Liver Transplant Registry between 1987-2005, we found: 1. The number of deceased-donor liver transplantations increased slowly each year, with most of the increase being in adult recipients. The number of LD transplants, on the other hand, decreased sharply after 2002, following 3 years of rapid increase from 1998-2001 in both pediatric and adult recipients. 2. The number of DD liver recipients with non-cholestatic liver diseases increased very quickly during the past 18 years. Malignant disease as a cause of end-stage liver disease increased after implementation of MELD in 2002. Among LD liver recipients, non-cholestatic disease increased sharply from 1998-2001, but decreased from 2002. Malignant diseases as a cause for LD transplants decreased after 2002. 3. Among pediatric recipients, LD transplants provided better 5-year graft survival rates than transplants from deceased donors; in contrast, LD transplants in adults had poorer graft survival rates than those from deceased donors. 4. The use of marginal donors, including older donors, HCV (+) donors, donation after cardiac death donors, and diabetic donors, increased in the past 18 years. HCV(+) livers transplanted into HCV(+) cirrhosis recipients had similar graft survival when compared with HCV(-) donor livers, whereas when they were transplanted into non-HCV cirrhosis patients, they had poorer graft survival (60% vs. 70% at 5 years, respectively). When livers from diabetic donors were transplanted into diabetic recipients, they had much poorer graft survival than transplants from non-diabetic donors (54% vs. 77% at 5 years, respectively). 5. Split and partial liver transplants had poorer 5-year graft survival rates (58% and 57%, respectively) than whole liver transplants (62%), but the difference was mainly due to poorer outcomes during the first posttransplant year. 6. PELD allocation has resulted in improved one- and 3-year graft survival rates among pediatric liver recipients. Among adults MELD-based allocation has resulted in better one-year survival rates. When comparing the different original diseases, only HCC patients showed better one- and 3-year graft survival rates after MELD. 7. Within one year after transplantation, primary non-function and infection were the major causes of graft failure. These decreased after 1996, but recurrent hepatitis has increased as a cause of graft failure. After one year, chronic rejection and infection had decreased, while hepatitis recurrence still increased. 8. Cardiovascular deaths and deaths from multiorgan failure that occurred within the first year after transplantation have increased since 1996, while deaths due to infections have decreased. After the first year, deaths from graft failure increased, while CVD and infections decreased.

One hundred fourteen living-donor liver transplants were performed at Tokyo University hospital from 1996-2000, including 66 children and 48 adults. Most (86%) of the children were transplanted for biliary atresia, whereas adults were more often transplanted for primary biliary cirrhosis (40%) or liver cirrhosis (23%) due to hepatitis or other unknown causes. Among children, 52% received the left lobe lateral segment, 23% an extended lateral segment and 21% the left lobe. The graft volume to standard liver ratio averaged 84%. Among adults, 79% received a left lobe; however, we have used the right lobe for most recent cases (21%) to provide sufficient volume. Parents donated to the pediatric recipients about 95% of the time, but a variety of family members donated for the adult transplants. The actual overall 3- and 5-year patient survival rates were 88.6% and 87.7%, respectively, and were slightly higher in children than adults. The results are comparable to those achieved with cadaver livers.

In the past decade liver transplantation has become the standard therapy for terminal liver failure. An increasing organ shortage, specific regional allocation systems within the Eurotransplant area and the lack of an efficient system to identify donors have resulted in decreasing numbers of liver transplants. Approximately 20% of patients are dying on the waiting list, a list that has exploded in numbers and waiting time in the past 3 years. In particular children and small adults are put at a disadvantage since standard donors have standard size livers. Two options to solve this dilemma are the expanded use of split-liver and living-donor liver transplantation. The specific experiences applying these techniques at the Medizinische Hochschule Hannover are discussed and compared with the results given in the European Liver Transplant Registry. The retrospective analysis demonstrates a shift in the use of resources, with decreasing numbers of full-size cadaver liver transplants and an increase in split- and living-donor liver transplantation. Both techniques are limited to specific patient populations, a notion that has to be considered in the comparison of results and outcome. According to our experience the full-size cadaver liver is still the standard option, while other techniques require careful attention to the chosen recipient population, advanced surgical skills and, for living donors, as a sine qua non the prerequisite of nihil nocere.

Liver transplantation remains the only definitive therapy for patients with decompensated liver disease. Significant advances over the past 20 years in surgical technique, immunosuppressive agents, patient selection, and infection prophylaxis and treatment have led to improved patient and graft survival. The success of liver transplantation coupled with expanding indications has resulted in a marked shortage of donor organs. Our approach at the University of Wisconsin to address the shortage of liver allografts is to maximize organ donation and recovery, include the use of liver allografts from donation after cardiac death, the use of split liver transplant, and the use of living-donor liver transplant when necessary. Split-liver transplantation is an effective technique to expand the number of organs available for transplantation. Continued improvements in organ preservation remain a priority to maximize outcomes, especially when the use of marginal donors or split-liver transplantation is planned. Recipient selection criteria have been expanded to include older recipients as well as previous recipients of multiple allografts. Over time it has become clear that less intensive immunosuppression is required since many patients can be maintained on tacrolimus monotherapy. We remain committed to a continued evaluation of donor and recipient factors in order to maximize outcomes of liver transplantation, as well as a critical appraisal of current and newer immunosuppressive agents and their effects on long-term outcome and recurrent disease.

The liver transplant program at the University of Pennsylvania and the Children's Hospital of Philadelphia experienced healthy growth in its clinical activity in the past 5 years. Patterns of referral and patient evaluation were established, care of patients while waiting on the list or being followed after transplantation was streamlined. We are now achieving excellent outcomes while transplanting relatively sicker patients. Innovative surgical procedures are implemented resulting in more efficient utilization of cadaveric and living-donor liver grafts. The protocols that are used for patient care are more standard, yet flexible and accommodate recent advancement in transplantation immunobiology. This progress of the clinical program was enhanced by careful preservation of the academic mission of the institution, which encourages the liver transplant faculty to be involved in NIH-supported clinical and basic science research.

In the past 6 years, advances in surgical technique and immunosuppression regimens have improved overall survival of transplant patients. Hepatitis C and alcoholic cirrhosis are the most common indications for transplantation at this center in the adult population while biliary atresia remains the most common indication in children. Organ shortages remain the most formidable obstacle to widespread application of organ transplantation. As recipient indications and criteria for transplantation expand, the number of patients awaiting organs increases. Simultaneously, donor criteria has not expanded and overall donor numbers have not increased substantially. We have used several approaches to alleviate the shortage of organs for both adults and children. Living-related donor transplantation yields excellent results and the operation can be done in an elective setting; however, it places an otherwise healthy person at risk. It is justified on basis of good results and the present shortage of organs. In-situ split-liver transplantation presents the opportunity to transplant children with size-matched organs without reducing the adult cadaveric pool. It is limited by the technical expertise required to perform the procedure safely. It can reduce the need to resort to living donor transplantation and is routinely used as the first option for pediatric patients awaiting transplantation at UCLA. Our results show that good results can be achieved with strict donor and recipient selection. In situ splitting has had a substantial impact on decreasing the pediatric waiting list time at our institution. Small bowel transplantation results have been improving; however, the complications related to the heavy immunosuppressive regimens need to be resolved.

Because of the unique demographics of our patient population, we have had the opportunity to dedicate further studies of the management of hepatitis B and hepatitis C. We have experienced a very low HBV recurrence rate with the use of HBIG in patients transplanted for hepatitis B. Investigations, including the use of new antiviral agents, and the development of approaches to minimize or abrogate disease recurrence such as lower levels of immunosuppression are ongoing. Using a standardized approach to the proper evaluation and selection of patients for liver transplantation with alcoholic liver disease or other liver diseases with coexistent alcohol abuse, we report favorable long-term results in these patients. We have reviewed our results and our approach to the management of EBV and posttransplant lymphoproliferative disorder. There is a firm commitment in our laboratories and outpatient clinics to the investigation of disease prevention, reliable detection and screening methods, and treatment modalities for EBV-related disease. We have addressed specific technical considerations to pediatric liver transplant and have discussed unique aspects of postoperative management in these patients. One-third of the transplants performed at Stanford are in children, 42% of whom are less than one year old. Results with our pediatric transplant recipients compare favorably with those of our adult recipients with patient and graft survival rates approaching 90% at one year and exceeding 80% at 46 months for both groups. As a response to the limited organ supply, we have extended our criteria for suitable donors. Most notably, we have utilized older donors and grafts with significant microsteatosis and have observed good results with these grafts as long as ischemia time is minimized. We have also successfully used reduced size grafts for our pediatric patients with good results and are continuing to expand the use of living-related partial grafts and split allografts.

The program of the University of Hamburg is exemplary of the problems faced by programs with rapid growth. Establishing expertise at all levels is essential to shorten the inevitable learning curve. The combination of an adult and a pediatric program was an ideal environment for the development of living donation and cadaveric in-situ split liver transplantation as complimentary solutions to eliminate pediatric mortality on the waiting list without affecting the chances of adult liver transplant candidates.

During the past 12 years, the Mayo Clinic Liver Transplant Program has continued to flourish. Not only has the program steadily grown in the numbers of patients transplanted, but now we are achieving an overall 90% one-year survival rate and have reduced our median posttransplant hospital stay to 9 days. Furthermore, a protocolized approach to the procedure has allowed us to continuously evaluate the appropriate use of resources and has allowed us to decrease the use of certain laboratory tests, reduce the use of radiologic and invasive procedures, and improve the overall cost efficiency. The challenge of the future will be to deal with recurrent disease and retransplantation. We desperately need treatment to prevent the recurrence of hepatitis B and C and, finally, we continue to search for immunosuppressive therapies that are less toxic and less costly.

Centers: The growth in liver transplantation activity recorded by the Pitt-UNOS Liver Transplant Registry since October 1987 continued. However, for the first time since the establishment of the LTR, there was no net gain in the number of centers in 1995. The large differences in volume per center also diminished., Patients: The age of pediatric recipients increased significantly in 1995, due to a decrease in the proportion of recipients under age one. For the first time, in 1995 fewer than half of transplantations in children were for biliary atresia. The addition of bone marrow transplantations, for which collection began in 1994, accounted for half of the multi-organ transplantations in 1995. Many of the characteristics examined for adult recipients changed between 1994 and 1995. The proportion of Hispanic recipients increased. The mean age of adult recipients continued to increase, but there was not a significant change in the prevalence of positive CMV serology. Reversing a trend, the proportion of adult recipients awaiting transplantation outside of the hospital decreased between 1994 and 1995. As with children, the proportion of adult multi-organ transplantations which included bone marrow increased. Hepatitis non-A, non-B, or C and alcoholic liver disease (ALD) were the most common reasons for LTX in 1995. While the proportion of recipients with ALD alone decreased slightly, the proportion with ALD and hepatitis C increased from 1994 to 1995., Outcome: The cumulative probability of surviving (without retransplantation) for 8 years after initial transplantation was .71 (.60) for pediatric recipients. The one-year survival for pediatric recipients changed significantly over time with the increase from 1994 to 1995 being similar to the increase between 1994 and prior years. Independent risk factors for survival among children included age, race, location awaiting transplantation, primary liver disease, and serum creatinine. Year of transplantation and bilirubin were independently associated with retransplantation-free survival, whereas multi-organ transplantation was associated with poorer patient survival. The cumulative probability of adults surviving (without retransplantation) for 7 years following LTX was .58 (.50). Independent risk factors were year of transplantation, age, location awaiting transplantation, primary liver disease, albumin, creatinine, and ABO match. Black recipients had poorer patient survival rates than other recipients whereas increased prothrombin time and CMV-positive donors were risk factors for retransplantation or death.