Faculty Bibliography

OBJECTIVE: To quantify the independent association between obesity and access to liver transplantation. BACKGROUND: Obesity is associated with higher complication rates, longer hospitalization, and worse survival after liver transplantation. Nevertheless, transplantation provides survival benefit to patients with end-stage liver disease, regardless of body mass index (BMI). We hypothesized that, despite survival benefit, providers were reluctant to transplant obese patients because of the inherent difficulty of these cases and their inferior outcomes. Our goal was to quantify the independent association between BMI and waiting time for orthotopic liver transplantation as a surrogate marker for this reluctance. METHODS: We studied 29,136 wait-list candidates in the model for end-stage liver disease (MELD) era, categorized as severely obese (BMI 35-40), morbidly obese (BMI 40-60), and reference (BMI 18.5-35). All models were adjusted for factors relevant to the allocation system, factors possibly influencing access to healthcare, and factors biologically related to disease progression and outcomes. RESULTS: The odds of receiving a MELD exception were 30% lower in severely obese and 38% lower in morbidly obese patients. Similarly, the likelihoods of being turned down for an organ were 10% and 16% higher, and the rates of being transplanted were 11% and 29% lower in severely obese and morbidly obese patients, respectively. CONCLUSIONS: Current practice seems to indicate a reluctance to transplant obese patients. If indeed as a community we feel that liver allografts should not be distributed to patients with excessive postoperative risk, we should consider expressing this as a formal change to our allocation policy rather than through informal practice patterns.

Although the majority of deceased-donor kidneys are donated after brain death, increased recovery of kidneys donated after cardiac death could reduce the organ shortage and is now a national priority. Racial disparities in donations after brain death have been well described for renal transplantation, but it is unknown whether similar disparities occur in donations after cardiac death. In this study, outcomes of adult deceased-donor renal transplant recipients included in the United Network for Organ Sharing database (1993 through 2006) were analyzed. Among black recipients of kidneys obtained after cardiac death, those who received kidneys from black donors had better long-term graft and patient survival than those who received kidneys from white donors. In addition, compared with standard-criteria kidneys from white donors after brain death, kidneys from black donors after cardiac death conferred a 70% reduction in the risk for graft loss (adjusted hazard ratio 0.30; 95% confidence interval 0.14 to 0.65; P = 0.002) and a 59% reduction in risk for death (adjusted hazard ratio 0.41; 95% confidence interval 0.2 to 0.87; P = 0.02) among black recipients. These findings suggest that kidneys obtained from black donors after cardiac death may afford the best long-term survival for black recipients.

BACKGROUND & AIMS/OBJECTIVE:Cholecystectomy is the most frequently performed gastrointestinal surgery in the United States. In this study, we characterized racial disparities in in-hospital mortality after cholecystectomy among patients with and without decompensated cirrhosis. METHODS:All patients who underwent cholecystectomy between 1998 and 2003 were queried from the Nationwide Inpatient Sample, the largest population-based and geographically representative all-payer database of hospital discharges in the United States. Crude mortality among races was determined for those with and without cirrhosis with portal hypertension and subsequently adjusted for demographic and clinical factors. RESULTS:In-hospital mortality associated with cholecystectomy was higher in the portal hypertensive group compared with those without portal hypertension (10.8% vs 1.4%; P < .0001). African Americans had greater adjusted mortality risk than whites in both the nonportal hypertensive (odds ratio [OR], 1.48; 95% CI, 1.35-1.63) and portal hypertensive (odds ratio [OR], 2.37; 95% CI, 1.47-3.84) groups, although the mortality gap was more pronounced in the latter. For portal hypertensive patients, undergoing cholecystectomy at a liver transplant center was associated with dramatically lower mortality (OR, 0.41; 95% CI, 0.25-0.69). CONCLUSIONS:In-patient mortality after cholecystectomy is 7.8-fold higher in patients with portal hypertension compared with those without portal hypertension. African Americans experienced higher mortality than whites after cholecystectomy, especially in the presence of portal hypertension. Cholecystectomy at a liver transplant center may offer survival benefit for patients with portal hypertension.

BACKGROUND: Kidney paired donation (KPD) offers the best transplant option for patients with incompatible live kidney donors. Although studies suggest substantial expansion of the donor pool if fully used, few patients in the United States have undergone KPD. METHODS: We analyzed the 209 KPD and 89 list paired donation (LPD) transplants reported to United Network for Organ Sharing to better understand access to these modalities, clinical outcomes, and areas of potential expansion. RESULTS: Although many centers offer KPD/LPD, most centers have performed no more than a handful of transplants. As expected, outcomes with KPD/LPD were equivalent to direct donation matched controls. In analyzing current practice, we identified two limitations to KPD in its current use. First, KPD is likely limited now by benefiting mostly patients who are easy to identify and match (such as A donors with B recipients or B donors with A recipients). Second, although some expansion of local KPD availability has reduced travel requirements for patients in those areas, significant room for growth remains. CONCLUSIONS: Our results suggest that full utilization of KPD would encourage registration of and improve matching for patients who are more difficult to identify and match (such as highly sensitized recipients). Furthermore, expansion of KPD would likely reduce travel requirements and thereby improve access to this treatment modality.

PURPOSE OF REVIEW/OBJECTIVE:Recently, four organ recipients were infected with HIV through transplantation, raising questions about current serologic testing policies. Currently, the decision to use enzyme-linked immunosorbent assay or nucleic acid testing, an expensive and time-consuming method capable of detecting more recent infections, is left up to individual organ procurement organizations. The purpose of this review was to present estimates of the window period between infection and detection by enzyme-linked immunosorbent assay and nucleic acid testing for HIV, hepatitis B virus, and hepatitis C virus; and to evaluate the impact of those infections on posttransplant outcomes. RECENT FINDINGS/RESULTS:Nucleic acid testing for HIV can detect infections 12-13 days earlier than enzyme-linked immunosorbent assay; in the case of hepatitis B virus, infections are detected 21.8-36 days earlier; and in the case of hepatitis C virus, infections are detected 26-60 days earlier. Studies indicate that it is possible to manage all three infections posttransplant. HIV/hepatitis C virus coinfections seem to present the greatest posttransplant management challenges due to drug toxicities. SUMMARY/CONCLUSIONS:Nucleic acid testing can reduce the window period and thus increase the probability of detecting viral infections. HIV, hepatitis B virus, and hepatitis C virus positive organs may be appropriate for use in some situations; nucleic acid testing helps patients and physicians make informed decisions about their use.

BACKGROUND: When the United Network for Organ Sharing changed its algorithm for liver allocation to the model for end-stage liver disease (MELD) system in 2002, highest priority shifted to patients with renal insufficiency as a major component of their end-stage liver disease. An unintended consequence of the new system was a rapid increase in the number of simultaneous liver-kidney transplants (SLK) being performed yearly. METHODS: Adult recipients of deceased donor liver transplants (LT, n=19,137), kidney transplants (n=33,712), and SLK transplants (n=1,032) between 1987 and 2006 were evaluated based on United Network for Organ Sharing data. Recipients were stratified by donor subgroup, MELD score, pre- versus post-MELD era, and length of time on dialysis. Matched-control analyses were performed, and graft and patient survival were analyzed by Kaplan-Meier and Cox proportional hazards analyses. RESULTS: MELD era outcomes demonstrate a decline in patient survival after SLK. Using matched-control analysis, we are unable to demonstrate a benefit in the SLK cohort compared with LT, despite the fact that higher quality allografts are being used for SLK. Subgroup analysis of the SLK cohort did demonstrate an increase in overall 1-year patient and liver graft survival only in those patients on long-term dialysis (> or =3 months) compared with LT (84.5% vs. 70.8%, P=0.008; hazards ratio 0.57 [95% CI 0.34, 0.95], P=0.03). CONCLUSION: These findings suggest that SLK may be overused in the MELD era and that current prioritization of kidney grafts to those liver failure patients results in wasting of limited resources.

Steroid use after liver transplantation (LT) has been associated with diabetes, hypertension, hyperlipidemia, obesity, and hepatitis C (HCV) recurrence. We performed meta-analysis and meta-regression of 30 publications representing 19 randomized trials that compared steroid-free with steroid-based immunosuppression (IS). There were no differences in death, graft loss, and infection. Steroid-free recipients demonstrated a trend toward reduced hypertension [relative risk (RR) 0.84, P = 0.08], and statistically significant decreases in cholesterol (standard mean difference -0.41, P < 0.001) and cytomegalovirus (RR 0.52, P = 0.001). In studies where steroids were replaced by another IS agent, the risks of diabetes (RR 0.29, P < 0.001), rejection (RR 0.68, P = 0.03), and severe rejection (RR 0.37, P = 0.001) were markedly lower in steroid-free arms. In studies in which steroids were not replaced, rejection rates were higher in steroid-free arms (RR 1.31, P = 0.02) and reduction of diabetes was attenuated (RR 0.74, P = 0.2). HCV recurrence was lower with steroid avoidance and, although no individual trial reached statistical significance, meta-analysis demonstrated this important effect (RR 0.90, P = 0.03). However, we emphasize the heterogeneity of trials performed to date and, as such, do not recommend basing clinical guidelines on our conclusions. We believe that a large, multicenter trial will better define the role of steroid-free regimens in LT.

Current billing practices and mandates to report surgical outcomes are disincentives to surgical treatment of obese patients, who are at increased risk for longer hospital stays and higher complication rates. The objective of this study was to quantify the independent association between body mass index (BMI) and waiting time for kidney transplantation to identify potential provider bias against surgical treatment of the obese. A secondary data analysis was performed of a prospective cohort of 132,353 patients who were registered for kidney transplantation in the United States between 1995 and 2006. Among all patients awaiting kidney transplantation, the likelihood of receiving a transplant decreased with increasing degree of obesity, categorized by ranges of BMI (adjusted hazard ratios 0.96 for overweight, 0.93 for obese, 0.72 for severely obese, and 0.56 for morbidly obese, compared with a reference group of patients with normal BMI). Similarly, the likelihood of being bypassed when an organ became available increased in a graded manner with category of obesity (adjusted incidence rate ratio 1.02 for overweight, 1.05 for obese, 1.11 for severely obese, and 1.22 for morbidly obese). Although matching an available organ with an appropriate recipient requires clinical judgment, which could not be fully captured in this study, the observed differences are dramatic and warrant further studies to understand this effect better and to design a system that is less susceptible to unintended bias.

CONTEXT: Although risks associated with live kidney donation are low, there are few pathologic studies of kidneys from live donors, and possible risk factors for development of hypertension or renal insufficiency remain unknown. There are many studies of histopathologic changes in deceased donor kidneys and how these changes affect subsequent graft function; most are based on wedge rather than needle core biopsies. OBJECTIVE: To examine the frequency and severity of arterial fibrointimal thickening and other pathologic lesions in kidneys from healthy live donors and compare wedge and needle core biopsies as methods for evaluating these changes. DESIGN: For 36 of 332 live donor renal transplantations performed from January 2004 through November 2006, a wedge biopsy of the transplanted kidney was done prior to and/or after implantation, and a needle core biopsy was done postimplantation or during the ensuing 7 days. For these 36 allografts, we compared pathologic features of the wedge and core perioperative biopsies. RESULTS: Findings on core and wedge biopsies were similar, except for arterial fibrointimal thickening. Moderate thickening (Banff cv2) was present on 13 core biopsies, and mild thickening (cv1) was present on another 10; by contrast, no wedge biopsies showed cv2 lesions, and only 8 showed cv1. Arterial thickening on core but not wedge biopsies correlated significantly with increasing patient age. CONCLUSIONS: The findings indicate that needle core biopsies are superior to wedge biopsies for evaluating vascular changes in donor kidneys, and they suggest a need for studies correlating such changes with long-term outcomes of live donors, particularly older donors.