R. Bakthavatsalam

D-MELD, a Simple Predictor of Post Liver Transplant Mortality for Optimization of Donor/Recipient Matching

Numerous donor and recipient risk factors interact to influence the probability of survival after liver transplantation. We developed a statistic, D‐MELD, the product of donor age and preoperative MELD, calculated from laboratory values. Using the UNOS STAR national transplant data base, we analyzed survival for first liver transplant recipients with chronic liver failure from deceased after brain death donors. Preoperative D‐MELD score effectively stratified posttransplant survival. Using a cutoff D‐MELD score of 1600, we defined a subgroup of donor–recipient matches with significantly poorer short‐ and long‐term outcomes as measured by survival and length of stay (LOS). Avoidance of D‐MELD scores above 1600 improved results for subgroups of high‐risk patients with donor age ≥60 and those with preoperative MELD ≥30. D‐MELD ≥1600 accurately predicted worse outcome in recipients with and without hepatitis C. There is significant regional variation in average D‐MELD scores at transplant, however, regions with larger numbers of high D‐MELD matches do not have higher survival rates. D‐MELD is a simple, highly predictive tool for estimating outcomes after liver transplantation. This statistic could assist surgeons and their patients in making organ acceptance decisions. Applying D‐MELD to liver allocation could eliminate many donor/recipient matches likely to have inferior outcome.

Late-onset cytomegalovirus disease in liver transplant recipients despite antiviral prophylaxis.

Background. The incidence and impact of cytomegalovirus (CMV) disease that occurs despite CMV prophylaxis among liver transplant recipients have been incompletely defined. Methods. The incidence and risk factors for CMV disease during the first posttransplant year in a cohort of liver transplant recipients who received antiviral prophylaxis with oral ganciclovir were retrospectively analyzed using Cox proportional-hazard regression models. Results. CMV disease developed in 19 of 259 recipients (7% [95% confidence interval 0.04–0.11]) at a median of 4.5 months posttransplant, included syndrome (63%) or tissue-invasive disease (37%), and was independently associated with an increased risk of mortality during the first posttransplant year (hazard ratio 14 [95% confidence interval 3.8–54], P=0.0007). The incidence was higher (10/38 [26%] vs. 8/180 [4.5%], P<0.0001) in seronegative recipients (R−) of an organ from a seropositive donor (D+) compared with seropositive (R+) patients, respectively. D+R− status was the only variable significantly associated with CMV disease in multivariate analysis. Conclusions. Late CMV disease develops in a substantial proportion of D+R− recipients after prophylaxis is discontinued, is not accurately predicted by patient factors, and is associated with increased mortality. New strategies to identify D+R− patients at risk and to reduce the incidence and impact of late CMV disease in this group are warranted.

Combination of Peritubular C4d and Transplant Glomerulopathy Predicts Late Renal Allograft Failure

The histologic associations and clinical implications of peritubular capillary C4d staining from long-term renal allografts are unknown. We identified 99 renal transplant patients who underwent an allograft biopsy for renal dysfunction at least 10 yr after transplantation, 25 of whom were C4d-positive and 74 of whom were C4d-negative. The average time of the index biopsy from transplantation was 14 yr in both groups. Compared with C4d-negative patients, C4d-positive patients were younger at transplantation (29 +/- 13 versus 38 +/- 12 yr; P < 0.05) and were more likely to have received an allograft from a living donor (65 versus 35%; P < 0.001). C4d-positive patients had more inflammation, were more likely to have transplant glomerulopathy, and had worse graft outcome. The combined presence of C4d positivity, transplant glomerulopathy, and serum creatinine of >2.3 mg/dl at biopsy were very strong predictors of rapid graft loss. C4d alone did not independently predict graft loss. Retrospective staining of historical samples from C4d-positive patients demonstrated C4d deposition in the majority of cases. In summary, these data show that in long-term renal allografts, peritubular capillary staining for C4d occurs in approximately 25% of biopsies, can persist for many years after transplantation, and strongly predicts graft loss when combined with transplant glomerulopathy.

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.

Differential Rates of Ischemic Cholangiopathy and Graft Survival Associated With Induction Therapy in DCD Liver Transplantation

Transplantation utilizing donation after circulatory death (DCD) donors is associated with ischemic cholangiopathy (IC) and graft loss. The University of Washington (UW) DCD experience totals 89 DCD liver transplants performed between 2003 and 2011. Overall outcome after DCD liver transplantation at UW demonstrates Kaplan–Meier estimated 5‐year patient and graft survival rates of 81.6% and 75.6%, respectively, with the great majority of patient and graft losses occurring in the first‐year posttransplant from IC. Our program has almost exclusively utilized either anti‐thymocyte globulin (ATG) or basiliximab induction (86/89) for DCD liver transplantations. Analysis of the differential effect of induction agent on graft survival demonstrated graft survival of 96.9% at 1 year for ATG versus 75.9% for basiliximab (p = 0.013). The improved survival did not appear to be from a lower rate of rejection (21.9% vs. 22.2%) but rather a differential rate of IC, 35.2% for basiliximab versus 12.5% for ATG (p = 0.011). Multivariable analysis demonstrated induction agent to be independently associated with graft survival and IC free graft survival when analyzed against variables including donor age, fWIT, donor cold ischemia time and transplant era.

Outcomes of simultaneous liver and kidney transplantation in relation to a high level of preformed donor-specific antibodies

Background The protective effect of the liver allograft when simultaneously transplanted with a kidney in the setting of allosensitization is unclear. Methods We analyzed the significance of sensitization, defined based on positive cytotoxicity crossmatches, positive flow cytometry crossmatches, and/or the presence of high levels of donor-specific antibodies, on the outcomes of simultaneous liver and kidney (SLK) transplantation. We reviewed 56 SLK performed at our center through December 31, 2011 and identified 13 patients who met high sensitization criteria. Results Median patient survival was not significantly different: 86 months (95% confidence interval [CI], 47–135) for nonsensitized patients versus 151 months (95% CI, 4 to ∞) for sensitized patients (P=0.5). The 5-year survival was 67% (95% CI, 0.5–0.8) in the nonsensitized group and 64% (95% CI, 0.3–0.9) in the sensitized group. There were six renal allograft failures in the nonsensitized group but none in the sensitized group. The adjusted hazard ratios associated with the risk of death or the combined risk of death or renal allograft failure were 0.7 (95% CI, 0.1–3.8) and 0.4 (95% CI, 0.1–2.2) for sensitized versus nonsensitized patients. There were significantly more renal allograft rejections in the sensitized group (5 vs. 1; P=0.002) in the first year after transplantation, only one showing C4d positivity. Creatinine levels at 1 year after transplantation were similar: 1.5 mg/dL in the nonsensitized group versus 1.36 mg/dL in the sensitized group (P=0.6). Conclusion Sensitization does not appear to have a significant negative impact on the survival of SLK patients.

Serum Alkaline Phosphatase and Bilirubin Are Early Surrogate Markers for Ischemic Cholangiopathy and Graft Failure in Liver Transplantation From Donation After Circulatory Death

Liver transplantation with the use of donation after circulatory death (DCD) is associated with ischemic cholangiopathy (IC) often leading to graft loss. We hypothesized that serial postoperative analysis of alkaline phosphatase and bilirubin might identify patients who would later on develop ischemic cholangiopathy and/or graft loss, allowing early recognition and potentially retransplantation. The University of Washington DCD experience totals 89 DCD liver transplantations performed from 2003 to 2011 with Kaplan-Meier estimated 5-year patient and graft survival rates of 81.6% and 75.6%, respectively; 84/89 patients transplanted with DCD livers lived ≥ 60 days after transplantation and were analyzed. Serum bilirubin and alkaline phosphatase levels at 1 week, 2 week, 1 month, and 2 months after transplantation were analyzed. Two-month serum bilirubin and alkaline phosphatase proved to have the strongest associations with development of IC and graft failure. Two-month alkaline phosphatase of <100 U/L had a negative predictive value of 97% for development of IC. Two-month alkaline phosphatase demonstrated an inflection starting at >300 U/L strongly associated with development of IC (P < .0001). Serum bilirubin at 2 months was most strongly associated with graft failure within the 1st year with a strong inflection point at 2.5 mg/dL (P = .0001). All jaundiced recipients at 60 days after transplantation (bilirubin >2.5 mg/dL) developed graft failure within the 1st year (P < .0001). Use of these early surrogate markers could facilitate prioritization and early retransplantation for DCD liver recipients with allografts destined for failure.

LIVER DENDRITIC CELLS INDUCES FOXP3+ TREG AND LIVER GRAFT TOLERANCE IN A PD-L1 DEPENDENT MANNER: 1620

W. Li1, R. Bakthavatsalam2, Z. Meng3, J.D. Perkins4, J.D. Reyes4 1Hepato-biliary-pancreatic Surgery, Norman Bethune Medical college of JiLin University, ChangChun/CHINA, 2Transplantation, Dept. Of Surgery, Univ. of Washington, seattle/UNITED STATES OF AMERICA, 3Hepato-biliary-pancreatic Surgery, Norman Bethune Medical School of JiLin University, ChangChun/CHINA, 4Dept. Of Surgery, Div. Of Transplantation, University of Washington, seattle/UNITED STATES OF AMERICA