André A. S. Dick

The biopsied donor liver: Incorporating macrosteatosis into high-risk donor assessment†

To expand the donor liver pool, ways are sought to better define the limits of marginally transplantable organs. The Donor Risk Index (DRI) lists 7 donor characteristics, together with cold ischemia time and location of the donor, as risk factors for graft failure. We hypothesized that donor hepatic steatosis is an additional independent risk factor. We analyzed the Scientific Registry of Transplant Recipients for all adult liver transplants performed from October 1, 2003, through February 6, 2008, with grafts from deceased donors to identify donor characteristics and procurement logistics parameters predictive of decreased graft survival. A proportional hazard model of donor variables, including percent steatosis from higher‐risk donors, was created with graft survival as the primary outcome. Of 21,777 transplants, 5051 donors had percent macrovesicular steatosis recorded on donor liver biopsy. Compared to the 16,726 donors with no recorded liver biopsy, the donors with biopsied livers had a higher DRI, were older and more obese, and a higher percentage died from anoxia or stroke than from head trauma. The donors whose livers were biopsied became our study group. Factors most strongly associated with graft failure at 1 year after transplantation with livers from this high‐risk donor group were donor age, donor liver macrovesicular steatosis, cold ischemia time, and donation after cardiac death status. In conclusion, in a high‐risk donor group, macrovesicular steatosis is an independent risk factor for graft survival, along with other factors of the DRI including donor age, donor race, donation after cardiac death status, and cold ischemia time. Liver Transpl 16:874–884, 2010.

Recurrent low gamma-glutamyl Transpeptidase cholestasis following liver transplantation for bile salt export pump (BSEP) disease (posttransplant recurrent BSEP disease)

Bile salt export pump (BSEP) deficiency is a hereditary cholestatic syndrome that results from mutations in the ABCB11 (ATP‐binding cassette B11) gene. Severely affected patients develop end‐stage liver disease in the first decade of life. Liver transplantation has traditionally been thought of as curative for BSEP disease. We describe the clinical course of 6 patients who developed recurrent low γ‐glutamyl transpeptidase cholestasis, that mimicks BSEP disease, following transplantation. All had documented genetic defects in ABCB11 that were predicted to lead to a congenital absence of BSEP protein. The time to development of recurrence was variable; 4 underwent repeat liver transplantation for complications of recurrent disease and all 4 again developed recurrent disease after retransplantation. Siblings of these patients who also underwent liver transplantation for BSEP disease have not developed “recurrent” disease. Three of the patients with “recurrent” disease ultimately died, 2 as a direct result of complications of their liver disease. Liver Transpl 16:856–863, 2010.

Risk stratification of kidneys from donation after cardiac death donors and the utility of machine perfusion

Cantafio AW, Dick AAS, Halldorson JB, Bakthavatsalam R, Reyes JD, Perkins JD. Risk stratification of kidneys from donation after cardiac death donors and the utility of machine perfusion.
Clin Transplant 2011: 25: E530–E540.

A contemporary analysis of parenteral nutrition-associated liver disease in surgical infants

BACKGROUND/PURPOSE Despite advances in pediatric nutritional support and a renewed focus on management of intestinal failure, there are limited recent data regarding the risk of parenteral nutrition (PN)-associated liver disease in surgical infants. This study investigated the incidence of cholestasis from PN and risk factors for its development in this population. METHODS A retrospective review was performed of all neonates in our institution who underwent abdominal surgery and required postoperative PN from 2001 to 2006. Cholestasis was defined as 2 conjugated bilirubin levels greater than 2 mg/dL over 14 days. Nonparametric univariate analyses and multivariate logistic regression were used to model the likelihood of developing cholestasis. Median values with range are presented. RESULTS One hundred seventy-six infants met inclusion criteria, and patients received PN for 28 days (range, 2-256 days). The incidence of cholestasis was 24%. Cholestatic infants were born at an earlier gestational age (34 vs 36 weeks; P < .01), required a 3-fold longer PN duration (76 vs 21 days; P < .001), had longer inpatient stays (86 vs 29 days; P < .001), and were more likely to be discharged on PN. The median time to cholestasis was 23 days. Cholestasis was an early development; 77% of cholestatic infants developed cholestasis by 5 weeks of PN exposure. On multivariate regression, only prematurity was significantly associated with development of cholestasis (P < .05). CONCLUSION In this analysis, the development of PN-associated liver disease occurred early in the course of exposure to PN. These data help to define the time course and prognosis for PN-associated cholestasis in surgical infants.

Imaging of orthotopic liver transplantation: review.

Received September 23, 2010; accepted without revision September 23, 2010. 1Department of Radiology, University of Washington, VA Puget Sound Health Care System, 1660 S Columbian Way, S-114/Radiology, Mail Stop 358280, Seattle, WA 98108. Address correspondence to P. Bhargava (bhargp@u.washington.edu). 2Department of Radiology, University of Washington, Seattle, WA. 3Department of Surgery, University of Washington, Seattle, WA. AJR 2011;196:WS15–WS25 0361–803X/11/1963–S1

A Randomized Clinical Trial Testing the Anti-Inflammatory Effects of Preemptive Inhaled Nitric Oxide in Human Liver Transplantation

Decreases in endothelial nitric oxide synthase derived nitric oxide (NO) production during liver transplantation promotes injury. We hypothesized that preemptive inhaled NO (iNO) would improve allograft function (primary) and reduce complications post-transplantation (secondary). Patients at two university centers (Center A and B) were randomized to receive placebo (n = 20/center) or iNO (80 ppm, n = 20/center) during the operative phase of liver transplantation. Data were analyzed at set intervals for up to 9-months post-transplantation and compared between groups. Patient characteristics and outcomes were examined with the Mann-Whitney U test, Student t-test, logistic regression, repeated measures ANOVA, and Cox proportional hazards models. Combined and site stratified analyses were performed. MELD scores were significantly higher at Center B (22.5 vs. 19.5, p<0.0001), surgical times were greater at Center B (7.7 vs. 4.5 hrs, p<0.001) and warm ischemia times were greater at Center B (95.4 vs. 69.7 min, p<0.0001). No adverse metabolic or hematologic effects from iNO occurred. iNO enhanced allograft function indexed by liver function tests (Center B, p<0.05; and p<0.03 for ALT with center data combined) and reduced complications at 9-months (Center A and B, p = 0.0062, OR = 0.15, 95% CI (0.04, 0.59)). ICU (p = 0.47) and hospital length of stay (p = 0.49) were not decreased. iNO increased concentrations of nitrate (p<0.001), nitrite (p<0.001) and nitrosylhemoglobin (p<0.001), with nitrite being postulated as a protective mechanism. Mean costs of iNO were

Antibody-mediated rejection after intestinal transplantation.

1,020 per transplant. iNO was safe and improved allograft function at one center and trended toward improving allograft function at the other. ClinicalTrials.gov with registry number 00582010 and the following URL:http://clinicaltrials.gov/show/NCT00582010.

Donor hepatitis C sero-status does not impact survival in liver transplantation.

Purpose of reviewIn spite of impressive improvements in short-term outcomes for intestine transplant recipients, late allograft loss continues to plague the field. Attention has mostly been focused on T-cell-mediated cellular mechanisms of allograft rejection to explain these losses; however, as in other forms of solid-organ transplantation, especially kidney and heart, antibody-mediated mechanisms of acute and chronic allograft injury are increasingly being implicated. In this review, the mechanisms of B-cell- and humoral-mediated allograft injury will be briefly discussed along with the limited evidence that exist for invoking antibody-mediated rejection (AMR) as important in intestine transplantation. Recent findingsThe presence of donor-specific antibody has been reported to increase the incidence and severity of intestine allograft rejection and to worsen the overall prognosis for graft and patient. C4d staining in intestine biopsies is unreliable, and currently it is not possible to diagnose AMR with certainty in intestine transplantation. Treatment of presumed AMR in intestine recipients is purely anecdotal at this time. SummaryFurther basic and clinical research needs to be conducted to more confidently diagnose and treat AMR in intestinal transplantation.

Impact of obesity on children undergoing liver transplantation

BACKGROUND Liver disease caused by hepatitis C virus (HCV) is the main indication for liver transplantation (LT) among adults in the US. Recurrent HCV impairs patient and graft survival after LT. The high prevalence of HCV along with scarce organs has lead to increased utilization of HCV+ organs. We estimated the impact of HCV+ donors on patient and graft survival. MATERIAL AND METHODS We conducted a cohort study of LT recipients age 18 years or older from February 2002 through December 2012 utilizing UNOS data. We evaluated differences in patient characteristics between HCV+ and HCV- recipients. We also compared patient and graft survival between these groups and among HCV+ recipients who received HCV+ versus HCV- donor organs using the Kaplan-Meier estimator and multivariate stratified Cox regression models. RESULTS We identified 59,899 LT recipients. Among those, 1,695 (2.8%) were HCV+ who received HCV+ grafts. HCV+ recipients of HCV- grafts were more likely to be female, hospitalized, in the ICU, on a ventilator, had higher MELD scores, and higher bilirubin. Patient and graft survival at 1, 5, and 10 years in HCV+ recipients was inferior to HCV- recipients, but HCV+ recipients who received HCV+ versus HCV- grafts were equivalent. Multivariate regression revealed multiple variables associated with worse outcomes. CONCLUSIONS The use of HCV+ grafts in HCV+ recipients is not associated with worse outcomes. With the increase in HCV+ patients awaiting an organ, more consideration should be given to HCV+ donors.

Prevalence and outcomes of renal transplantation in children with intellectual disability.

Controversies exist with respect to the mortality of patients undergoing liver transplantation at the extremes of the body mass index (BMI). For pediatric liver transplantation, weight is usually the only factor considered in survival analysis. A review of the United Network for Organ Sharing database (1987‐2007) revealed 9701 pediatric patients (<18 years old) who underwent primary liver transplantation. Patients were stratified into 5 BMI categories established by the World Health Organization according to their Z score, which was based on age, gender, and BMI: −3, −2, 0, +2, and +3. The survival rates in these 5 categories were compared with Kaplan‐Meier survival curves and log‐rank testing. Patients with thinness (Z score = −2) and severe thinness (Z score = −3) had significantly (P < 0.0001) lower survival at 1 year (84.4%) versus the survival (88.7%) of the normal and overweight groups (Z score = 0 and Z score = + 2, respectively). For patients with obesity (Z score = +3), there was no significant difference in survival early after transplantation, but their mortality gradually increased in the later years after transplantation. By 12 years after liver transplantation, the obese group had significantly (P = 0.04) lower survival (72%) than the normal and overweight groups (77%). In conclusion, liver transplantation holds increased risk for obese pediatric patients. Thin pediatric patients experience early mortality after liver transplantation, and obese pediatric patients experience late mortality after liver transplantation. Transplant management can be modified to optimize the care of these patients. Liver Transpl 16:1296‐1302, 2010.