Faculty Bibliography

BACKGROUND:Initial therapy for early hepatocellular carcinoma (HCC) with well-compensated cirrhosis is controversial. While we previously reported on the effect of clinical factors and surgeon specialty on choice of therapy for early HCC, other nonclinical factors also may impact decision-making. METHODS:Surgeons who treat HCC were invited to complete a web-based survey that included ten case scenarios. Choice of therapy-liver transplantation (LT), liver resection (LR), or radiofrequency ablation (RFA)-was analyzed using regression models. RESULTS:There were 336 responses for analysis. Most respondents were in academic centers (86 %) that offered LT (71 %). The median number of patients annually evaluated for HCC was 30. Both practice type and HCC case volume were associated with choice of therapy, but these associations were not independent of surgeon specialty. LT surgeons who did not also perform RFA were less likely than those LT surgeons who did offer RFA to choose RFA over LT (relative risk ratios (RRR) 0.38, P < 0.001). Non-LT surgeons were more likely than LT surgeons who also offered RFA to choose RFA over LT (RRR 2.24, P < 0.001). Surgeons who worked at hospitals where LT was performed were much more likely to choose LT over LR and RFA even if they did not personally perform LT (RRR 1.27 and RRR 3.33, P < 0.001). CONCLUSIONS:Surgeon- and institution-related factors impact choice of therapy for early HCC even after adjustment for differences in clinical presentation. These data suggest that choice of therapy for patients with early HCC varies across providers independent of case selection.

BACKGROUND:Disparity in access to liver transplantation (LT) in the United States persists despite directives from the federal government to reduce geographic variation. We assessed the impact of socioeconomic status (SES) and traveling to alternative donation service areas (DSAs) on patient survival. METHODS:A prospective cohort study integrating transplant registry and U.S. Census data was analyzed using multivariate linear Cox proportional hazards models. A separate matched-pairs analysis was used to assess the benefit of traveling on patient survival and transplantation rate. RESULTS:High SES is associated with increased access to LT (adjusted hazard ratio [aHR], 1.05; 95% confidence interval [95% CI], 1.01-1.08) and reduced mortality after waitlisting (aHR [95% CI], 0.88 [0.85-0.93]). Increased access is mediated, in part, through inter-DSA travel. Travel was associated with high SES, white race, blood group O, private insurance, and residence in regions 1, 5, and 11. Transplant candidates in the highest SES quartile were approximately 70% more likely to travel (aHR [95% CI], 1.67 [1.43-1.97]) than those in the lowest SES quartile. Compared with matched control patients, travelers were 74% more likely to be transplanted (aHR [95% CI], 1.74 [1.56-1.94]) and 20% less likely to die after listing (aHR [95% CI], 0.79 [0.69-0.92]). CONCLUSION/CONCLUSIONS:High SES and inter-DSA travel are strongly associated with increased LT access and reduced mortality. Travelers are more likely to be sociodemographically advantaged and privately insured and to live in regions with reduced access to deceased-donor organs.

BACKGROUND AND OBJECTIVE/OBJECTIVE:The risk of graft loss after pediatric kidney transplantation increases during late adolescence and early adulthood, but the extent to which this phenomenon affects all recipients is unknown. This study explored interactions between recipient factors and this high-risk age window, searching for a recipient phenotype that may be less susceptible during this detrimental age interval. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:With use of Scientific Registry of Transplant Recipients data from 1987 to 2010, risk of graft loss across recipient age was quantified using a multivariable piecewise-constant hazard rate model with time-varying coefficients for recipient risk factors. RESULTS:Among 16,266 recipients, graft loss during ages ≥17 and <24 years was greater than that for both 3-17 years (adjusted hazard ratio [aHR], 1.61; P<0.001) and ≥24 years (aHR, 1.28; P<0.001). This finding was consistent across age at transplantation, sex, race, cause of renal disease, insurance type, pretransplant dialysis history, previous transplant, peak panel-reactive antibody (PRA), and type of induction immunosuppression. The high-risk window was seen in both living-donor and deceased-donor transplant recipients, at all levels of HLA mismatch, regardless of centers' pediatric transplant volume, and consistently over time. The relationship between graft loss risk and donor type, PRA, transplant history, insurance type, and cause of renal disease was diminished upon entry into the high-risk window. CONCLUSIONS:No recipient subgroups are exempt from the dramatic increase in graft loss during late adolescence and early adulthood, a high-risk window that modifies the relationship between typical recipient risk factors and graft loss.

The growth in living kidney donation has been accompanied by greater racial diversity. Most information on post-donation health comes from single-center studies of dominantly Caucasian cohorts. Recent linkage of U.S. donor registration data with death records demonstrated higher mortality risks among African American donors, but importantly, no differences in death compared with demographically matched, healthy controls. Within the donor population, some recent studies have also identified higher likelihoods of post-donation hypertension, diabetes mellitus and kidney failure in African American and Hispanic donors. Thus, based on concerns for higher risks of long-term end-organ damage, it may be reasonable to consider race within the living donor selection process, such as use of more stringent exclusion criteria among non-Caucasian living donors with baseline elevated blood pressure. Recently identified associations of coding variants in the apolipoprotein L1 (APOL1) gene with nondiabetic renal failure in African Americans raise promise of APOL1 genotyping as a novel tool for risk stratifying African American potential donors, but more data are needed to understand implications for post-donation outcomes. To tailor counseling and informed consent, focused attention to long-term medical outcomes among non-Caucasian living donors is needed, and should include assembly of healthy non-donor controls for assessment of attributable risks of donation.

BACKGROUND:Solid organ transplantation recipients have elevated cancer incidence. Estimates of absolute cancer risk after transplantation can inform prevention and screening. METHODS:The Transplant Cancer Match Study links the US transplantation registry with 14 state/regional cancer registries. The authors used nonparametric competing risk methods to estimate the cumulative incidence of cancer after transplantation for 2 periods (1987-1999 and 2000-2008). For recipients from 2000 to 2008, the 5-year cumulative incidence, stratified by organ, sex, and age at transplantation, was estimated for 6 preventable or screen-detectable cancers. For comparison, the 5-year cumulative incidence was calculated for the same cancers in the general population at representative ages using Surveillance, Epidemiology, and End Results data. RESULTS:Among 164,156 recipients, 8520 incident cancers were identified. The absolute cancer risk was slightly higher for recipients during the period from 2000 to 2008 than during the period from 1987 to 1999 (5-year cumulative incidence: 4.4% vs. 4.2%; P = .006); this difference arose from the decreasing risk of competing events (5-year cumulative incidence of death, graft failure, or retransplantation: 26.6% vs. 31.9%; P < .001). From 2000 to 2008, the 5-year cumulative incidence of non-Hodgkin lymphoma was highest at extremes of age, especially in thoracic organ recipients (ages 0-34 years: range, 1.74%-3.28%; aged >50 years; range, 0.36%-2.22%). For recipients aged >50 years, the 5-year cumulative incidence was higher for colorectal cancer (range, 0.33%-1.94%) than for the general population at the recommended screening age (aged 50 years: range, 0.25%-0.33%). For recipients aged >50 years, the 5-year cumulative incidence was high for lung cancer among thoracic organ recipients (range, 1.16%-3.87%) and for kidney cancer among kidney recipients (range, 0.53%-0.84%). The 5-year cumulative incidence for prostate cancer and breast cancer was similar or lower in transplantation recipients than at the recommended ages of screening in the general population. CONCLUSIONS:Subgroups of transplantation recipients have a high absolute risk of some cancers and may benefit from targeted prevention or screening.

OBJECTIVES/OBJECTIVE:To quantify the prevalence of frailty in adults of all ages undergoing chronic hemodialysis, its relationship to comorbidity and disability, and its association with adverse outcomes of mortality and hospitalization. DESIGN/METHODS:Prospective cohort study. SETTING/METHODS:Single hemodialysis center in Baltimore, Maryland. PARTICIPANTS/METHODS:One hundred forty-six individuals undergoing hemodialysis enrolled between January 2009 and March 2010 and followed through August 2012. MEASUREMENTS/METHODS:Frailty, comorbidity, and disability on enrollment in the study and subsequent mortality and hospitalizations. RESULTS:At enrollment, 50.0% of older (≥ 65) and 35.4% of younger (<65) individuals undergoing hemodialysis were frail; 35.9% and 29.3%, respectively, were intermediately frail. Three-year mortality was 16.2% for nonfrail, 34.4% for intermediately frail, and 40.2% for frail participants. Intermediate frailty and frailty were associated with a 2.7 times (95% confidence interval (CI) = 1.02-7.07, P = .046) and 2.6 times (95% CI = 1.04-6.49, P = .04) greater risk of death independent of age, sex, comorbidity, and disability. In the year after enrollment, median number of hospitalizations was 1 (interquartile range 0-3). The proportion with two or more hospitalizations was 28.2% for nonfrail, 25.5% for intermediately frail, and 42.6% for frail participants. Although intermediate frailty was not associated with number of hospitalizations (relative risk = 0.76, 95% CI = 0.49-1.16, P = .21), frailty was associated with 1.4 times (95% CI = 1.00-2.03, P = .049) more hospitalizations independent of age, sex, comorbidity, and disability. The association between frailty and mortality (interaction P = .64) and hospitalizations (P = .14) did not differ between older and younger participants. CONCLUSIONS:Adults of all ages undergoing hemodialysis have a high prevalence of frailty, more than five times as high as community-dwelling older adults. In this population, regardless of age, frailty is a strong, independent predictor of mortality and number of hospitalizations.

BACKGROUND:This study compares biliary complication rates associated with use of two different preservative solutions, Histidine-Tryptophan-Ketoglutarate (HTK) and University of Wisconsin (UW), utilized in orthotopic liver transplantation (LT) with donations after cardiac death (DCDs). MATERIAL AND METHODS/METHODS:Between 1997-2010, we retrospectively studied 35 LTs performed utilizing DCD donors, preserved either with HTK (n=17) or UW(n=18). Biliary complications were defined by the presence of anastomotic strictures, non-anastomotic strictures, and/or biliary leak on endoscopic retrograde cholangiopancreatography. RESULTS:HTK and UW cohorts were similar in terms of demographics as well as pre- and post-operative biochemical profile. Donor age was significantly higher among HTK compared to UW recipients (41.5 ± 11.9 vs. 26.2 ± 8.8 years, p<0.001). The incidence of post-LT biliary complications was higher in the HTK group (76% vs. 39% in UW group, p=0.041). Hepatic arterial thrombosis (HAT) was observed among 3 HTK patients (17.7%) and 1 UW patient (5.6%), p=0.33. No patients underwent retransplantation in UW group, five recipients in HTK group underwent retransplantation (29%), p=0.019; 4 due to biliary complications and 1 due to HAT. CONCLUSIONS:This single-center study reveals that the use of HTK preservative among DCD donors is associated with an increased risk of biliary complications. Multicenter retrospective studies are suggested to further verify this observation.

INTRODUCTION/BACKGROUND:Sirolimus has inhibitory effects on epithelial healing and cholangiocyte regeneration. In liver transplantation (LT) patients, these effects may be greatest at the biliary anastomosis. We therefore investigated whether sirolimus use is associated with need for early or emergent repeat therapeutic endoscopic retrograde cholangiography (ERC) in LT patients with anastomotic biliary stricture (ABS). MATERIAL AND METHODS/METHODS:Medical records of patients who underwent LT from 1998-2009 at Johns Hopkins were reviewed and patients with ABS identified. Primary outcome was early repeat ERC, defined as need for unscheduled (i.e. unplanned) or emergent repeat therapeutic ERC. Univariate and multivariate logistic regression analyses (adjusting for age, sex, LT to ERC time, and stent number) were performed to assess association between sirolimus and early repeat ERC. RESULTS:45 patients developed ABS and underwent 156 ERCs total. Early (median 26 days) repeat ERC occurred in 14/56 (25%) and 6/100 (6%) ERCs performed with and without concomitant sirolimus-based immunosuppression, respectively (OR 1.22; 95% CI 1.02-1.45; p = 0.03). In multivariate analysis, sirolimus use was associated with early repeat ERC (OR 1.24; 95% CI 1.04-1.47; p = 0.015); this association remained significant when sirolimus dose was modeled as a continuous variable (OR 1.04 for each mg of sirolimus per day; 95% CI 1.02-1.08; p = 0.038). CONCLUSIONS:Sirolimus-based immunosuppression appears to be associated with a modest but significantly increased, dose-dependent risk of early repeat ERC in LT patients with ABS. Prospective studies are needed to further investigate these findings and determine if sirolimus use or dose should potentially be reconsidered once ABS is diagnosed.