Predictors of survival following liver transplantation in infants: a single-center analysis of more than 200 cases.

BACKGROUND: Infants (<12 months) who require liver transplantation (LTx) represent a particularly challenging and understudied group of patients. METHODS: This retrospective study aimed to describe a large single-center experience of infants who received isolated LTx, illustrate important differences in infants versus older children, and identify pretransplant factors which influence survival. More than 25 pre-LTx demographic, laboratory, and operative variables were analyzed using the Log-rank test and Cox proportional hazards model. RESULTS: Between 1984 and 2006, 216 LTx were performed in 186 infants with a mean follow-up time of 62 months. Median age at LTx was 9 months, the majority had cholestatic liver disease, were hospitalized pre-LTx, and received whole grafts. Leading indications for re-LTx (n=30) included vascular complications (43%) and graft nonfunction (40%), whereas leading causes of death were sepsis and multiorgan failure. One-, 5-, and 10-year graft and patient survivals were 75%/72%/68% and 79%/77%/75%, respectively. Relative to older pediatric recipients, infants had worse overall patient survival (P=0.05). The following were significant univariate predictors of graft loss: age less than 6 months and reduced cadaveric grafts; and of patient loss: age less than 6 months, calculated CrCl less than 90, pre-LTx hospitalization, pre-LTx mechanical ventilation, repeat LTx, infants transplanted for reasons other than cholestatic liver disease, and patients transplanted between 1984 and 1994. CONCLUSIONS: Long-term outcomes for infants undergoing LTx are excellent and have improved over time. As the largest, single-center analysis of LTx in infants, this study elucidates a unique set of predictors that can aid in medical decision making.

Renal function impacts outcomes after intestinal transplantation.

BACKGROUND: Although renal dysfunction (RD) has been commonly associated with poor outcome after other solid organ transplants, it has not been studied in detail after intestinal transplantation (ITx). Here we provide a detailed analysis of renal function after ITx, and identify predictors of post-ITx RD. METHODS: A retrospective analysis of patients undergoing ITx from 1991 to 2006 was performed. For each patient, the estimated glomerular filtration rate (eGFR) was compared with the normal GFR for age and gender to obtain the percent of normal eGFR. Chi-square analysis and log-rank tests were used to identify categorical variables associated with RD (eGFR <75% of normal) and to determine if RD was predictive of post-ITx survival. RESULTS: Sixty-eight transplantations were performed in 62 patients. Overall patient survival at 1 and 5 years was 78% and 56%, respectively. Renal dysfunction was observed in 16% of patients post-ITx. The most frequent predictors of post-ITx RD were preoperative eGFR less than 75% of normal, pre-ITx location in the intensive care unit, and high-dose tacrolimus immunotherapy. An eGFR less than 75% of normal at days 7, 28, and 365 was predictive of poor patient survival (P<0.05). CONCLUSIONS: This study provides the first detailed analysis of renal function after ITx. We identified specific risk factors for the development of RD in the first year post-ITx and found a significant association of RD with decreased long-term survival. Given the strong correlation of RD with poor outcome, preserving renal function may be key to improving long-term outcomes in ITx recipients.

Predictors of outcomes after pediatric liver transplantation: an analysis of more than 800 cases performed at a single institution.

BACKGROUND: Pediatric liver transplantation (PLTx) is the standard of care for treatment of liver failure in children. Unfortunately, there are few studies with substantial numbers of patients that identify outcomes predictors. The goal of this study was to determine factors that influence outcomes in a large, single-center cohort of PLTx. STUDY DESIGN: This retrospective review between 1984 to 2006 included all recipients 18 years of age and younger undergoing PLTx. Multiorgan graft recipients were excluded (n = 48). Data sources included transplantation center database and hospital medical records. Outcomes measures were overall patient and graft survival. Demographic, laboratory, and perioperative variables were analyzed. Univariate and multivariate statistical analysis was undertaken using log-rank test and Cox's proportional hazards model. A p value < 0.05 was considered significant at the multivariate level. RESULTS: Eight hundred fifty-two PLTx were performed in 657 children; 55% were girls, 45% were Hispanic, and median age was 29.5 months. Biliary atresia and acute liver failure were the most common causes of liver disease. Fifty-two percent were hospitalized before PLTx. Graft types were whole (75%) and segmental (25%). Indications for re-PLTx (n = 195) included graft nonfunction (22%), immunologic (34%), and vascular complications (35%). Overall 1-, 5-, and 10-year survival rates were 85%, 81%, and 78% (patient), and 78%, 72%, and 67% (graft). Independent significant predictors of worse patient survival were renal function, pretransplantation ventilator dependence, and causes of liver disease. Independent significant predictors of worse graft survival were renal function and warm ischemia time. CONCLUSIONS: As one of the largest, single-center analyses of PLTx, this study enables accurate statistical analysis and demonstrates excellent longterm outcomes. Independent prognosticators of graft survival were renal function and warm ischemia time, and those for patient survival were renal function, mechanical ventilation, and causes of liver disease. These factors can aid in the medical decision making required for optimal use of scarce donor organs.

Effect of nonviral factors on hepatitis C recurrence after liver transplantation.

OBJECTIVE: Hepatitis C (HCV) is now the most common indication for orthotopic liver transplantation (OLT). While graft reinfection remains universal, progression to graft cirrhosis is highly variable. This study examined donor, recipient, and operative variables to identify factors that affect recurrence of HCV post-OLT to facilitate graft-recipient matching. METHODS: Retrospective review of 307 patients who underwent OLT for HCV over a 10-year period at our center. Recurrence of HCV was identified by the presence of biochemical graft dysfunction and concurrent liver biopsy showing diagnostic pathologic features. Time to recurrence was the endpoint for statistical analysis. Five donor, 6 recipient, and 2 operative variables that may affect recurrence were analyzed by univariate comparison and Cox proportional hazard regression models. RESULTS: Recurrence-free survival in the 307 study patients was 69% and 34% at 1 and 5 years, respectively. Four predictive variables related to either donor or recipient characteristics were identified. Advanced donor age, prolonged donor hospitalization, increasing recipient age, and elevated recipient MELD scores were found to increase the relative risk of HCV recurrence. Examination of HLA disparity between donors and recipients demonstrated no correlation between class I or class II mismatches and recurrence-free survival. CONCLUSIONS: We have identified donor and recipient characteristics that significantly predict hepatitis C recurrence following liver transplantation. These factors are identifiable before transplant and, if considered when matching donors to HCV recipients, may decrease the incidence of HCV recurrence after OLT. A change in the current national liver allocation system would be needed to realize the full value of this benefit.

Optimal utilization of donor grafts with extended criteria: a single-center experience in over 1000 liver transplants.

OBJECTIVE: Severely limited organ resources mandate maximum utilization of donor allografts for orthotopic liver transplantation (OLT). This work aimed to identify factors that impact survival outcomes for extended criteria donors (ECD) and developed an ECD scoring system to facilitate graft-recipient matching and optimize utilization of ECDs. METHODS: Retrospective analysis of over 1000 primary adult OLTs at UCLA. Extended criteria (EC) considered included donor age (>55 years), donor hospital stay (>5 days), cold ischemia time (>10 hours), and warm ischemia time (>40 minutes). One point was assigned for each extended criterion. Cox proportional hazard regression model was used for multivariate analysis. RESULTS: Of 1153 allografts considered in the study, 568 organs exhibited no extended criteria (0 score), while 429, 135 and 21 donor allografts exhibited an EC score of 1, 2 and 3, respectively. Overall 1-year patient survival rates were 88%, 82%, 77% and 48% for recipients with EC scores of 0, 1, 2 and 3 respectively (P < 0.001). Adjusting for recipient age and urgency at the time of transplantation, multivariate analysis identified an ascending mortality risk ratio of 1.4 and 1.8 compared to a score of 0 for an EC score of 1, and 2 (P < 0.01) respectively. In contrast, an EC score of 3 was associated with a mortality risk ratio of 4.5 (P < 0.001). Further, advanced recipient age linearly increased the death hazard ratio, while an urgent recipient status increased the risk ratio of death by 50%. CONCLUSIONS: Extended criteria donors can be scored using readily available parameters. Optimizing perioperative variables and matching ECD allografts to appropriately selected recipients are crucial to maintain acceptable outcomes and represent a preferable alternative to both high waiting list mortality and to a potentially futile transplant that utilizes an ECD for a critically ill recipient.

Analysis of long-term outcomes of 3200 liver transplantations over two decades: a single-center experience.

OBJECTIVE: Few studies have evaluated long-term outcomes after orthotopic liver transplantation (OLT). This work analyzes the experience of nearly 2 decades by the same team in a single center. Outcomes of OLT and factors affecting survival were analyzed. METHODS: Retrospective analysis of 3200 consecutive OLTs that were performed at our institution, between February 1984 and December 31, 2001. RESULTS: Of 2662 recipients, 578 (21.7%) and 659 (24.7%) were pediatric and urgent patients, respectively. Overall 1-, 5-, 10-, and 15-year patient and graft survival estimates were 81%, 72%, 68%, 64% and 73%, 64%, 59%, 55%, respectively. Patient survival significantly improved in the second (1992-2001) versus the era I (1984-1991) of transplantation (P < 0.001). Similarly, graft survival was better in the era II of transplantation (P < 0.02). However, biliary and infectious complications increased in era II. When OLT indications were considered, best recipient survival was obtained in children with biliary atresia (82%, 79%, and 78% at 1, 5, and 10 years, respectively), while malignant disease in adult patients resulted in the worst outcomes of 68% and 43% at 1 and 5 years, post-OLT. Further, patients <18 years and nonurgent recipients exhibited superior survival when compared with recipients >18 years (P < 0.001) or urgent patients (P < 0.001). Of 13 donor and recipient variables, era of OLT, recipient age, urgent status, donor age, donor length of hospital stay, etiology of liver disease, retransplantation, warm and cold ischemia, but not graft type (whole, split, living-donor), significantly impacted patient survival. CONCLUSIONS: Long-term benefits of OLT are greatest in pediatric and nonurgent patients. Multiple factors involving the recipient, etiology of liver disease, donor characteristics, operative variables, and surgical experience influence long-term survival outcomes. By balancing and matching these factors with a given recipient, optimum results can be achieved.

Fulminant liver failure due to usnic acid for weight loss.

The use of complementary and alternative medicine (CAM) in developed countries has increased significantly over the years. Among the most popular are the weight loss supplements or "fat burners." Liver failure due to these popular remedies has been widely recognized. Usnic acid has been an ingredient of dietary supplements that cause liver failure. Its hepatotoxicity has not been recognized because it is usually mixed with other ingredients that are presumably hepatotoxic. We describe a case of a 28-yr-old woman who presented with fulminant liver failure requiring orthotopic liver transplantation, after taking pure usnic acid for weight loss. This is the first report on fulminant liver failure associated with the ingestion of pure usnic acid. A discussion about hepatotoxicity of the different compounds of dietary supplements is presented. This is a reminder for the clinicians about the potential side effects of CAM.