A case for a national registry of red blood cell antibodies.

BACKGROUND AND OBJECTIVES: Red blood cell (RBC) antibody levels diminish over time and negative antibody screen are commonly seen in patients with a history of antibodies. Most hospitals do not have access to a shared registry of antibodies previously detected at other hospitals. MATERIALS AND METHODS: We describe a case where the patient was found to be at high risk of bleeding during liver transplantation. Antibody screen on admission was negative but a history of anti-Jka was identified on reviewing patient's history in local registry of RBC antibodies. The surgery was pushed back to arrange for antigen-negative units. The patient received a total of 16 Jk(a-) RBC units during the admission. RESULTS: No acute or delayed transfusion adverse reactions were seen. However, if the history of anti-Jka identified at another local hospital was not known, approximately three-quarters of the units transfused would have been Jk(a+). Transfusing Jk(a+) units could have potentially exposed the patient to risk of developing an acute and/or delayed haemolytic transfusion reaction which could have led to significant morbidity and perhaps mortality. CONCLUSION: With this case report, we build a case for developing a national registry of RBC antibodies to help improve patient safety and outcomes.

Degree of Glomerulosclerosis in Procurement Kidney Biopsies from Marginal Donor Kidneys and Their Implications in Predicting Graft Outcomes.

Background: This study aimed to assess the association between the percentage of glomerulosclerosis (GS) in procurement allograft biopsies from high-risk deceased donor and graft outcomes in kidney transplant recipients. Methods: The UNOS database was used to identify deceased-donor kidneys with a kidney donor profile index (KDPI) score > 85% from 2005 to 2014. Deceased donor kidneys were categorized based on the percentage of GS: 0-10%, 11-20%, >20% and no biopsy performed. The outcome included death-censored graft survival, patient survival, rate of delayed graft function, and 1-year acute rejection. Results: Of 22,006 kidneys, 91.2% were biopsied showing 0-10% GS (58.0%), 11-20% GS (13.5%), >20% GS (19.7%); 8.8% were not biopsied. The rate of kidney discard was 48.5%; 33.6% in 0-10% GS, 68.9% in 11-20% GS, and 77.4% in >20% GS. 49.8% of kidneys were discarded in those that were not biopsied. Death-censored graft survival at 5 years was 75.8% for 0-10% GS, 70.9% for >10% GS, and 74.8% for the no biopsy group. Among kidneys with >10% GS, there was no significant difference in death-censored graft survival between 11-20% GS and >20% GS. Recipients with >10% GS had an increased risk of graft failure (HR = 1.27, p < 0.001), compared with 0-10% GS. There was no significant difference in patient survival, acute rejection at 1-year, and delayed graft function between 0% and 10% GS and >10% GS. Conclusion: In >85% KDPI kidneys, our study suggested that discard rates increased with higher percentages of GS, and GS >10% is an independent prognostic factor for graft failure. Due to organ shortage, future studies are needed to identify strategies to use these marginal kidneys safely and improve outcomes.

Intratumoral CD3 and CD8 T-cell Densities Associated with Relapse-Free Survival in HCC.

Immune cells that infiltrate a tumor may be a prognostic factor for patients who have had surgically resected hepatocellular carcinoma (HCC). The density of intratumoral total (CD3(+)) and cytotoxic (CD8(+)) T lymphocytes was measured in the tumor interior and in the invasive margin of 65 stage I to IV HCC tissue specimens from a single cohort. Immune cell density in the interior and margin was converted to a binary score (0, low; 1, high), which was correlated with tumor recurrence and relapse-free survival (RFS). In addition, the expression of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) was correlated with the density of CD3(+) and CD8(+) cells and clinical outcome. High densities of both CD3(+) and CD8(+) T cells in both the interior and margin, along with corresponding Immunoscores, were significantly associated with a low rate of recurrence (P = 0.007) and a prolonged RFS (P = 0.002). In multivariate logistic regression models adjusted for vascular invasion and cellular differentiation, both CD3(+) and CD8(+) cell densities predicted recurrence, with odds ratios of 5.8 [95% confidence interval (CI), 1.6-21.8] for CD3(+) and 3.9 (95% CI, 1.1-14.1) for CD8(+) Positive PD-L1 staining was correlated with high CD3 and CD8 density (P = 0.024 and 0.005, respectively) and predicted a lower rate of recurrence (P = 0.034), as well as prolonged RFS (P = 0.029). Immunoscore and PD-L1 expression, therefore, are useful prognostic markers in patients with HCC who have undergone primary tumor resection. Cancer Immunol Res; 4(5); 419-30. ©2016 AACR.

A case of a ruptured sclerosing liver hemangioma.

Hemangiomas are the most common benign tumors found in the liver, typically asymptomatic, solitary, and incidentally discovered. Although vascular in nature, they rarely bleed. We report a case of a 52-year-old woman with a previously stable hemangioma who presented to our hospital with signs and symptoms indicative of spontaneous rupture. We review the literature, focusing on diagnosis and management of liver hemangiomas.

Association between donor-specific antibodies and acute rejection and resolution in small bowel and multivisceral transplantation.

BACKGROUND: Donor-specific antibodies (DSA) are associated with acute kidney graft rejection, but their role in small bowel/multivisceral allograft remains unclear. We carried out a prospective study to understand the impact of DSA in the setting of intestinal allograft rejection. METHODS: Thirteen patients (15 grafts) were serially evaluated for DSA levels pre- and posttransplant. DSA was determined by Luminex and the results were interpreted as fluorescence intensity (FI), with FI more than 3000 considered positive. RESULTS: The clinical rejection episodes in allografts were significantly associated with the presence of DSA (P=0.041).We obtained 291 biopsy samples from graft ileum and date-matched DSA assay reports. Sixty-three (21.65%) of the biopsies showed acute rejection. The appearance of DSA were preformed (n=5, anti-human leukocyte antigen class II=3, anti-class I and II=2), de novo (n=4, 15.25±4.72 days after transplantation, anti-class II=1, and anti-class I and II=3) and never (n=6). Among the 63 biopsies, 30(47.6%) had significant correlations with positive DSA (kappa=0.30, P<0.001) and manifested severe rejection grade (P=0.009). CONCLUSIONS: In this cohort of small bowel/multivisceral transplantation patients, there was a high incidence of DSA. The presence of DSA should alert the clinical team of a higher risk of rejection, and reduction of the FI is clinically associated with resolution. Serial endoscopy guided biopsies combined with simultaneous DSA measurement in postintestinal transplantation follow-up is an effective means of screening for cellular and humoral-based forms of acute rejection.

Characteristic immune, apoptosis and inflammatory gene profiles associated with intestinal acute cellular rejection in formalin-fixed paraffin-embedded mucosal biopsies.

Small bowel transplantation (SBT) is becoming a preferred treatment for patients with irreversible intestinal failure. Despite continuous improvement of immunosuppression, SBT is plagued by a high incidence of acute cellular rejection (ACR) that is frequently intractable. Therefore, there is a need for reliable detection markers and novel immunosuppressive strategies that can achieve better control of ACR. We hypothesized that particular transcriptomes provide critical regulation of the intragraft immune response. The aim of our study was to detect potential molecular biomarkers for identifying ACR in minute mucosal biopsies. We examined 30 intestinal mucosal biopsies (AR/NR; 17/13) obtained from recipients after SBT or multivisceral transplantation. We utilized TaqMan® Gene Signature Arrays (immune, inflammation and apoptosis) and investigated the expression of 280 genes. As one of our validations, we performed immunohistochemistry for selected targets. We detected 252 mRNAs in total, 92 of which were found with significantly different expression levels between the AR and NR groups. Immunohistochemistry showed significantly increased staining for IL1R2, ICAM1, GZMB, and CCL3 (P < 0.05) during ACR. For the first time, we characterize the potential molecular changes that are associated with modulation of histological appearances of intestinal ACR. These differences in transcriptome patterns can be used to identify robust biomarkers and potential novel therapeutic targets for immunosuppressive agents.

Liver transplantation using elderly donors: a risk factor analysis.

Survival after liver transplantation is negatively impacted by use of elderly deceased donors, but excluding them would increase waiting times and waiting list mortality. We reviewed our experience with liver transplantation (LT) utilizing livers from deceased donors 65 yr of age and older to identify those factors that impact graft survival. All adult patients (≥ 18 yr old) who underwent primary LT using deceased donor livers from donors aged ≥ 65 yr between February 1995 and November 2003 were included. With multivariate analysis we found four unfavorable characteristics significantly associated with higher post-transplant graft failure rate. These characteristics are hepatitis C as an etiology of liver disease, Model for End-Stage Liver Disease score >20, serum glucose level of donor > 200 mg/dL at the time of liver recovery, and skin incision to aortic cross-clamp time > 40 minutes in the donor surgery. The five-yr estimated graft survival rates having 0, 1, 2, 3, and 4 unfavorable characteristics were 100%, 82.0%, 81.7%, 39.3%, and 25.0%, respectively (p < 0.05). Our data demonstrated good graft survival can be achieved in LT using elderly donor liver allografts with appropriate patient selection, donor blood glucose management and efficient liver recovery with minimal manipulation of the liver during donor surgery.

Long-term follow-up of 23 operational tolerant liver transplant recipients.

INTRODUCTION: This is a follow-up of a withdrawal study that we previously performed on 104 liver transplant patients in which immunosuppression was gradually withdrawn over a period of 3 years. Eighty-one patients were not able to be withdrawn (rejectors), and 23 patients were successfully weaned off immunosuppression (tolerants). METHODS: In this study, we present their follow-up after the end of the withdrawal study: we compared the results of the tolerant patients (n=23) with those of the rejectors (n=81). Follow-up was until February 2010. RESULTS: Operational tolerant patients were off immunosuppression for an average of 7.27±0.28 years. Patient survival in the tolerant and the rejector groups was 63.66% and 74.25%, respectively (P=not significant). A patient in the rejector group received two retransplants for chronic rejection. In the rejector group, 19 patients presented 26 rejection episodes: clinically suspected (n=19) and biopsy-proven mild (n=4), moderate (n=2), and severe (n=1) rejection episodes. A tolerant patient had a moderate rejection episode of 5.3 years after immunosuppression withdrawal. In the rejector group, five patients received a kidney transplant and four more are on dialysis versus a tolerant patient on dialysis. Freedom from rejection in the tolerant and rejector groups was 95% and 73%, respectively (P<0.05), and freedom from renal replacement treatment was 83.33% vs. 44.58%, respectively (P=not significant). CONCLUSIONS: Long-term outcomes of operationally tolerant liver transplant patients are at least as good as those of control patients. Operational tolerance is not a permanent state, and continuous vigilance is required to detect rejection episodes.

Liver transplantation for hepatocellular carcinoma in the model for end-stage liver disease era.

BACKGROUND: Since March 2002, the United Network for Organ Sharing liver allocation policy has given extra priority to patients with hepatocellular carcinoma (HCC) who meet specific medical criteria. This study reviews our experience with liver transplantation for HCC under this system. STUDY DESIGN: Between March 2002 and April 2009, 244 patients with HCC underwent primary liver or liver-kidney transplantation under the current allocation system at the University of Miami. Outcomes including HCC recurrence-free survival (RFS) and patient survival (PS) were assessed retrospectively. Clinical variables that predicted outcomes were analyzed. RESULTS: The median time from listing to transplantation was 48 days. The median follow-up was 27.4 months, with an observed recurrence rate of 10.7%. The RFS rates at 1, 3, and 5 years after transplantation were 96.0%, 89.0%, and 83.6%, respectively. The PS rates at 1, 3, and 5 years after transplantation were 86.3%, 71.5%, and 61.7%, respectively. Among patients diagnosed with T2 HCC, a trend toward improved RFS was observed for those who received preoperative ablative therapy; PS was similar (p > 0.05). Outcomes (RFS and PS) for patients with T3 HCC were similar to those in patients with T2 HCC (p > 0.05). Patients with an alpha-fetoprotein >100 ng/mL had an RFS that was inferior to that in patients with an alpha-fetoprotein < or =100 ng/mL (p < 0.0001). CONCLUSIONS: Under the current allocation system, transplantation for HCC results in excellent RFS; PS depends on factors other than HCC; the value of preoperative ablative therapy for patients with T2 HCC is uncertain; the current criteria could be expanded to include selected patients with T3 HCC; and an elevated AFP level is associated with an increased risk of HCC recurrence after transplantation.

Effect of liver transplantation on spleen size, collateral veins, and platelet counts.

BACKGROUND: The aim of this study was to evaluate the effect of liver transplantation on the spleen size, spontaneous splenorenal shunt (SRS) function, and platelet counts in patients with hypersplenism. METHODS: Between December 2001 and February 2007, 462 adult patients underwent orthotopic liver transplantations (OLTX) at our institution. Of these patients, CT or MRI information was reviewed retrospectively in 55 patients. Volume measurements of the spleen and liver, spleen/liver volume ratio (S/L ratio), presence and size of SRS, and platelet counts were evaluated before and after OLTX. RESULTS: Mean spleen volume decreased from 827 +/- 463 ml to 662 +/- 376 ml after OLTX (p < 0.01). Five (11%) patients returned to normal-range spleen size after OLTX. SRS was observed in 19 patients before OLTX (35%). The diameter of SRS also significantly decreased from 1.0 +/- 0.5 cm before OLTX to 0.7 +/- 0.5 cm after OLTX (p < 0.05). SRS disappeared in 16% of patients (3/19). S/L ratio significantly decreased from 0.65 +/- 0.33 to 0.38 +/- 0.17 (p < 0.01) after OLTX. Platelet counts significantly increased after OLTX (p < 0.01). Improvement of the platelet count in the group with postoperative S/L ratio >0.35 was not as good as that in the group with S/L ratio <0.35 (p < 0.01). CONCLUSIONS: Spleen size and SRS size became significantly smaller after OLTX. However, patients with postoperative S/L ratio >0.35 tend to have lower platelet counts after OLTX.

Liver retransplantation of more than two grafts for recurrent failure.

BACKGROUND: Transplantation of more than two livers for recurring graft failure has not been specifically addressed in the literature. METHODS: A retrospective analysis was conducted from a total of 2527 overall liver transplants at our institution. Main indications for multiple retransplant included primary nonfunction, chronic rejection, hepatic artery thrombosis, and recurrent disease. RESULTS: We identified 39 patients who received more than two grafts (32 received 3 grafts, 5 received 4 grafts, and 2 received 5 grafts). All patients required interposition arterial grafts from the aorta and hepatojejunostomy for the biliary reconstruction. Seventeen patients are still alive at last follow-up. Perioperative mortality rates after 3rd, 4th, and 5th liver graft were 25%, 14%, and 50%, respectively. Patient and graft survival rates were 72% and 56% at 1 year, respectively. Median length of stay was 27 days and median graft survival was 2.9 years. CONCLUSIONS: Selection of patients and a significant use of available resources are some of the important factors that clinicians need to take into account when dealing with multiple retransplantations. With such conditions, however, liver retransplantation of more than two grafts can be a life-saving procedure.

Mass clamping of the hilum to facilitate difficult hepatectomy during liver transplantation: a single center 10 year experience.

INTRODUCTION: Classic dissection of the hilar structures during the hepatectomy portion of the liver transplant procedure is sometimes extremely difficult and even dangerous. In such cases, clamping of the hepatic hilar structures en mass can be an effective alternative. In this study, we describe our center's experience with this technique. PATIENTS AND METHODS: This is a retrospective analysis of all patients who received a liver allograft using this technique at our center, between September 1996 and September 2007 (n = 150). Postoperative follow-up was through November 30, 2007. RESULTS: One hundred fifty patients underwent 155 liver transplants using hilar mass clamping. These cases represent 7% of the total number of cases performed at our center during that time interval (n = 2219). This included 93 male and 57 female patients, 18 children and 132 adults. There were 103 primary liver transplants, 52 retransplants. Three of the primary transplants were combined liver/kidney transplants. In 7 cases (4.5%), portacaval hemitransposition was performed to establish portal flow.The decision to perform the hepatectomy with mass clamping of the hilar structures was an intraoperative judgment made when severe vascular adhesions and scarring of the hilum (n = 137) or extensive hilar varices (n = 18) were encountered. The hilar pathology was often associated with hepatic artery (n = 15) or portal vein thrombosis (n = 14).Mean surgical time was 11.33 +/- 0.28 hours. Average blood replacement was 26.27 +/- 2.05 units of packed red blood cells. One patient died intraoperatively (0.64%) while perioperative (30 day) mortality was 6.4%. Venovenous by pass was used in 1 patient (0.64%).One and 5 year patient survival was 75.3% and 61.2%, respectively. One and 5 year graft survival was 73.7% and 48.2%, respectively. There was no patient mortality, graft loss, or technical complications that could be attributed to the mass clamp technique. CONCLUSION: Mass clamping of the hepatic hilum can be an effective alternative to classic hilar dissection in cases when the latter is difficult or impossible.

Intestinal and multivisceral transplantation at the University of Miami.

At the University of Miami Liver and GI Transplant Program, over 300 intestinal transplant procedures were performed in the last 15 years in adult and pediatric recipients. Good patient and graft survival rates are now achievable. Rejection remains the complication that is most difficult to prevent and manage. Induction with antilymphocyte agents, followed by maintenance with tacrolimus, is the preferred immunosuppression protocol at our center. We have expanded the use of multivisceral transplantation in pediatric recipients with short gut and significant liver dysfunction from parenteral nutrition. We also advocate the use of large intestine as part of the intestinal graft as well as inclusion of the spleen in multivisceral grafts, which in our experience can be safely accomplished. The future of intestinal transplantation lies in the use of noninvasive markers of intestinal rejection, and continued refinements in immunosuppression protocols.

Successful treatment with bortezomib of a refractory humoral rejection of the intestine after multivisceral transplantation.

Graft rejection is a serious complication after intestinal and multivisceral transplantation. Classic anti-rejection strategies often focus on addressing the cellular component, however mounting evidence suggests that antibody mediated rejection may also play an important role in patient and graft survival. Bortezomib, a proteasome inhibitor used in the treatment of multiple myeloma, has been found to be useful in treating antibody mediated rejection in kidney transplant recipients. The following case illustrates how bortezomib was used to successfully reverse refractory rejection in a patient following multivisceral transplantation. While the rejection was able to be controlled, this patient's course was complicated by an aggressive viral infection after bortezomib therapy. Bortezomib may be a useful agent in the treatment of rejection after intestinal and multivisceral transplantation; however more data is needed to assess its impact on infectious complications in this complex group of patients.

Analysis of acute and chronic rejection in multiple organ allografts from retransplantation and autopsy cases of multivisceral transplantation.

BACKGROUND: Small intestinal allografts in multivisceral transplantation are felt to be more susceptible to acute cellular rejection (ACR) and chronic rejection (CR) when compared with other allografts although there is little direct evidence for this impression. METHODS: A total of 48 cases of multiple allograft specimens (37 autopsy and 11 explanted allograft cases) from 41 patients were evaluated in this study. Histopathologic assessments were performed with special concern to ACR and CR in allografts. The numbers of allografts available for evaluation were liver 37, small intestine 47, stomach 41, pancreas 45, and large intestine 25. RESULTS: Among 48 cases, 15 cases showed ACR (ACR case) and 12 showed CR (CR case) in at least one organ. In ACR cases, there was a statistically significant difference of organ-specific susceptibility to ACR among multivisceral allografts with the small intestinal allograft being the most susceptible (P<0.05). Severe ACR were observed only in small and large intestinal allografts. In CR cases, there was no statistically significant difference of organ-specific susceptibility to CR among multivisceral allografts with a tendency for the pancreas allograft to be the most susceptible (P=0.35). CONCLUSIONS: Our study clearly indicated variation in organ susceptibility to ACR and CR. Small intestinal allografts were the most susceptible organ to ACR in frequency and severity. Pancreatic allografts may be more susceptible to CR in comparison with ACR.

Fecal calprotectin level measurements in small bowel allograft monitoring: a pilot study.

BACKGROUND: Protocol endoscopy with biopsy is currently the gold standard of small bowel transplantation (SBTx) monitoring, however it is invasive, costly, needs skilled operator, may require anesthesia and may cause complications. We investigated fecal calprotectin level (FCL) as a candidate noninvasive marker for monitoring patients after SBTx. METHODS: A pilot study was performed to test the use of FCL measurement in following up SBTx patients. Ileostomy effluents were collected at various postoperative days before endoscopy and biopsy. FCLs were measured by enzyme-linked immunosorbent assay and a cut-off level of 100 ng/mg was considered positive. The results were retrospectively evaluated in combination with clinical, endoscopic, and histopathological findings. FCLs are presented as median nanogram per milligram. RESULTS: FCLs were measured in 122 samples that were obtained from 29 patients after SBTx. Only 1 of 69 positive FCL did not accompany abnormal findings. Retrospective evaluation showed that 11 samples from six patients (FCL: 217) coincided with rejection episodes, six samples from three patients (FCL: 125) coincided with viral enteritis, 51 samples from 21 patients (FCL: 207) coincided with nonspecific inflammation, 11 samples from two patients (FCL: 998) coincided with chronic intestinal ulceration, and finally 50 samples from 19 patients (FCL: 43) coincided with normal findings. No significant FCL difference was found between rejection, infection, and inflammation. FCL evolution in individuals showed that FCL can predict rejection days before histopathological diagnosis. CONCLUSION: FCL is a sensitive test for ongoing organic intestinal allograft pathologies. It might be useful as prescreening marker to avoid unnecessary endoscopies.

Transplantation of the spleen: effect of splenic allograft in human multivisceral transplantation.

OBJECTIVES: To describe the effect of the splenic allograft in human multivisceral transplantation. SUMMARY BACKGROUND DATA: We performed transplants of the spleen as part of a multivisceral graft in an attempt to decrease both the risk of infection from an asplenic state and the risk of rejection by a possible tolerogenic effect. To our knowledge, this is the first report of human splenic transplantation in a large series. METHODS: All primary multivisceral recipients who received a donor spleen (N = 60) were compared with those who did not receive a spleen (N = 81). RESULTS: Thirty-five of 60 (58%) are alive in the spleen group, and 39 of 81 (48%) are alive in control group (P = 0.98). In univariate analysis, splenic recipients showed superiority in freedom-from-any rejection (P = 0.02) and freedom-from-moderate or severe rejection (P = 0.007). No significant differences were observed in analyses of infectious complications between the spleen and control groups. Both platelet and leukocyte counts became normal in splenic patients, whereas these counts were significantly increased in nonsplenic recipients. Observed incidence of graft versus host disease (GVHD) was 8.25% (5 of 60) in the spleen group and 6.2% (5 of 81) in the control group (P = 0.70). Increased incidence of autoimmune hemolysis was observed in the spleen group. CONCLUSIONS: Allograft spleen can be transplanted within a multivisceral graft without significantly increasing the risk of GVHD. The allogenic spleen seems to show a protective effect on small bowel rejection. Further investigation with longitudinal follow-up is required to precisely determine the immunologic and hematologic effects of the allograft spleen.

A cause-specific hazard rate analysis of prognostic factors among 877 adults who received primary orthotopic liver transplantation.

BACKGROUND: In orthotopic liver transplantation (OLT) distinct causes of graft failure (GF) and death with a functioning graft (DFG) exist. Prognostic factors for one failure type may be distinctly different from those predictive of other types, and an accurate portrayal of these relationships may more clearly explain each factor's importance. METHODS: A multivariable cause-specific hazard (CSH) rate analysis using Cox stepwise regression was performed among 877 adults who received primary OLT during 1996-2004 with tacrolimus+steroids as immunosuppression. RESULTS: Older donor age (P=0.004) implied greater primary dysfunction GF, while primary sclerosing cholangitis (PSC; P=0.0002) implied greater vascular thrombosis GF. Recurrent nonmalignant liver disease GF was higher among hepatitis C virus patients (P<0.00001), and younger recipient age (P=0.005) implied greater death from recurrent (metastatic) hepatocellular carcinoma. African-American race (P<0.00001), PSC (P=0.003), and younger recipient age (P=0.005) were independently associated with greater GF due to chronic rejection. Older donor age (P=0.003) implied greater infection DFG, while older recipient age (P=0.003) and pretransplant diabetes (P=0.03) were independently associated with greater cardiovascular/cerebrovascular DFG. Finally, most of these cause-specific predictors were not significant in an overall Cox model for graft survival. CONCLUSIONS: The CSH approach should be more widely used in investigations of prognostic factors. The result of older donor age implying greater primary dysfunction GF and infection DFG but having no association with other failure types demonstrates that its impact is specific to the graft's early posttransplant functional status. In addition, while recipient age was an important prognosticator, its direction of association reverses depending upon the outcome being analyzed.

Twenty-year experience with liver transplantation for hepatocellular carcinoma.

HYPOTHESIS: Liver transplantation (LT) has become the optimal treatment for stages I and II hepatocellular carcinoma (HCC). Based on our 20-year experience, changes in staging, techniques, and patient selection have improved survival over the past 20 years. Herein, we determine if pre-LT treatment for HCC alters the long-term outcomes in patients with HCC. DESIGN: Outcomes study. SETTING: Tertiary referral center. PATIENTS: We retrospectively reviewed prospectively collected data in a cohort of 92 patients who underwent LT for HCC between 1983 and 2003. MAIN OUTCOME MEASURES: Patient demographics, tumor stage in the explant liver, patient survival, and tumor recurrence data were analyzed. RESULTS: The average follow-up was 1052 (range, 0-6491) days. The average tumor size was 3.6 cm; 40% of tumors were multifocal and 60% unifocal. Of the 92 patients, 26% were classified as stage I; 42%, stage II; 24%, stage III; and 8%, stage IV. The overall 5-year survival rate was 50%, the 10-year survival rate was 32%, and the 15-year survival rate was 27%. Improvements in staging in the last 5 years reduced the number of patients with stages III and IV HCC from 39% to 19% and increased the 5-year survival rate to 69%. Tumor recurrence was relatively rare (13%); however, recurrence resulted in a poor prognosis (75% mortality rate; P = .02). The average time to recurrence was 458 (range, 179-1195) days. CONCLUSIONS: Liver transplantation for HCC results in excellent long-term survival for patients with stages I and II HCC, with relatively few patients dying from tumor recurrence. Improvements in preoperative staging have resulted in increased 5-year survival rates. Further refinements in pre-LT staging may increase the effectiveness of LT for HCC.